Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021

ilustraciones, fotografías, graficas

Autores:
Gallo Gomez, Yeinson Nabor
Tipo de recurso:
Fecha de publicación:
2021
Institución:
Universidad Nacional de Colombia
Repositorio:
Universidad Nacional de Colombia
Idioma:
spa
OAI Identifier:
oai:repositorio.unal.edu.co:unal/83061
Acceso en línea:
https://repositorio.unal.edu.co/handle/unal/83061
https://repositorio.unal.edu.co/
Palabra clave:
610 - Medicina y salud
ARN Mensajero
Herpesvirus Humano 4
Núcleo Familiar
Métodos
Fibra de Lana
Neoplasias gástricas
Patología molecular
Inmunohistoquímica
Hibridación fluorescente in situ
Stomach Neoplasms
Molecular Pathology
Immunohistochemistry
In Situ Hybridization, Fluorescence
Rights
openAccess
License
Reconocimiento 4.0 Internacional
id UNACIONAL2_f5b8461f6a8191cd641ab2eb8a5c2368
oai_identifier_str oai:repositorio.unal.edu.co:unal/83061
network_acronym_str UNACIONAL2
network_name_str Universidad Nacional de Colombia
repository_id_str
dc.title.spa.fl_str_mv Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
dc.title.translated.eng.fl_str_mv Evaluation of the molecular classification of gastric cancer by immunohistochemistry and in situ hybridization and its relationship with the expression of PD-L1 and patients of the Hospital Universitario Nacional between 2016 and 2021
title Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
spellingShingle Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
610 - Medicina y salud
ARN Mensajero
Herpesvirus Humano 4
Núcleo Familiar
Métodos
Fibra de Lana
Neoplasias gástricas
Patología molecular
Inmunohistoquímica
Hibridación fluorescente in situ
Stomach Neoplasms
Molecular Pathology
Immunohistochemistry
In Situ Hybridization, Fluorescence
title_short Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
title_full Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
title_fullStr Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
title_full_unstemmed Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
title_sort Evaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021
dc.creator.fl_str_mv Gallo Gomez, Yeinson Nabor
dc.contributor.advisor.none.fl_str_mv Franco Tavera, Oscar Andres
dc.contributor.author.none.fl_str_mv Gallo Gomez, Yeinson Nabor
dc.contributor.researchgroup.spa.fl_str_mv Anatomopatología
dc.contributor.orcid.spa.fl_str_mv Gallo Gomez, Nabor (0000-0003-3795-4660)
dc.contributor.cvlac.spa.fl_str_mv Gallo Gomez, Yeinson Nabor (0001600796)
dc.subject.ddc.spa.fl_str_mv 610 - Medicina y salud
topic 610 - Medicina y salud
ARN Mensajero
Herpesvirus Humano 4
Núcleo Familiar
Métodos
Fibra de Lana
Neoplasias gástricas
Patología molecular
Inmunohistoquímica
Hibridación fluorescente in situ
Stomach Neoplasms
Molecular Pathology
Immunohistochemistry
In Situ Hybridization, Fluorescence
dc.subject.other.spa.fl_str_mv ARN Mensajero
Herpesvirus Humano 4
Núcleo Familiar
Métodos
Fibra de Lana
dc.subject.proposal.spa.fl_str_mv Neoplasias gástricas
Patología molecular
Inmunohistoquímica
Hibridación fluorescente in situ
dc.subject.proposal.eng.fl_str_mv Stomach Neoplasms
Molecular Pathology
Immunohistochemistry
In Situ Hybridization, Fluorescence
description ilustraciones, fotografías, graficas
publishDate 2021
dc.date.issued.none.fl_str_mv 2021
dc.date.accessioned.none.fl_str_mv 2023-01-23T15:47:14Z
dc.date.available.none.fl_str_mv 2023-01-23T15:47:14Z
dc.type.spa.fl_str_mv Trabajo de grado - Especialidad Médica
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv Text
dc.type.redcol.spa.fl_str_mv http://purl.org/redcol/resource_type/TM
status_str acceptedVersion
dc.identifier.uri.none.fl_str_mv https://repositorio.unal.edu.co/handle/unal/83061
dc.identifier.instname.spa.fl_str_mv Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv https://repositorio.unal.edu.co/
url https://repositorio.unal.edu.co/handle/unal/83061
https://repositorio.unal.edu.co/
identifier_str_mv Universidad Nacional de Colombia
Repositorio Institucional Universidad Nacional de Colombia
dc.language.iso.spa.fl_str_mv spa
language spa
dc.relation.references.spa.fl_str_mv 1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.
2. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018; 10:239-48.
3. Sun Y, Yu W, Guan W, Cai L, Qiao M, Zheng L, Jiang R, Wang R, Wang L. Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer. Cancer Manag Res. 2019; 11: 6397-410.
4. Lahmidani N, et al. Update on Gastric Cancer Epidemiology and Risk Factors. Journal of Cancer Therapy. 2018; 9:242-54.
5. Network CGAR. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517):202-9.
6. Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015; 21(5):449-56.
7. Birkman EM, Mansuri N, Kurki S, Ålgars A, Lintunen M, Ristamäki R, Sundström J, Carpén O. Gastric cancer: immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics. Virchows Arch. 2018; 472(3): p. 369-82.
8. R Oliveros, RE Pinilla, H Facundo-Navia, R Sánchez-Pedraza. Cáncer gástrico: una enfermedad prevenible. Estrategias para intervención en la historia natural. Rev. colomb. Gastroenterol. 2019; 34(2): 177-89.
9. Díaz Del Arco C, Estrada Muñoz L, Molina Roldán E, Cerón Nieto MÁ, Ortega Medina L, García Gómez de Las Heras S, Fernández Aceñero MJ. Immunohistochemical classification of gastric cancer based on new molecular biomarkers: a potential predictor of survival. Virchows Arch. 2018; 473(3): p. 687-95.
10. Kim HS, Shin SJ, Beom SH, Jung M, Choi YY, Son T, Kim HI, Cheong JH, Hyung WJ, Noh SH, Chung H, Park JC, Shin SK, Lee SK, Lee YC, Koom WS, Lim JS, Chung HC, Rha SY, Kim H. Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy. Oncotarget. 2016; 7(28): 44608-20.
11. Ahn S, Lee SJ, Kim Y, Kim A, Shin N, Choi KU, Lee CH, Huh GY, Kim KM, Setia N, Lauwers GY, Park DY.. High-throughput Protein and mRNA Expression-based Classification of Gastric Cancers Can Identify Clinically Distinct Subtypes, Concordant With Recent Molecular Classifications. 2017; 41(1): 106-15.
12. Setia N, Agoston AT, Han HS, Mullen JT, Duda DG, Clark JW, Deshpande V, Mino-Kenudson M, Srivastava A, Lennerz JK, Hong TS, Kwak EL, Lauwers GYA protein and mRNA expression-based classification of gastric cancer. Mod Pathol. 2016; 29(7): 772-84.
13. Gonzalez RS, Messing S, Tu X, McMahon LA, Whitney-Miller CL. Immunohistochemistry as a surrogate for molecular subtyping of gastric adenocarcinoma. Hum Pathol. 2016; 56: 16-21.
14. Park CK, Park JS, Kim HS, Rha SY, Hyung WJ, Cheong JH, Noh SH, Lee SK, Lee YC, Huh YM, Kim H. Receptor tyrosine kinase amplified gastric cancer: Receptor tyrosine kinase amplified gastric cancer: Clinicopathologic characteristics and proposed screening algorithm. Oncotarget. 2016; 7(44):72099-112.
15. Sun Y,Yu W, Guan W, Qiao M, Zheng L,Jiang R,. Wang R, Wang L.Assessment of molecular classification of gastric cancer by immunohistochemistry and in situ hybridization: A validation study in the Chinese population. Ann Oncol. 2018; 29(9): mdy432.018.
16. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010; 127(12): p. 2893-917.
17. Jemal A BFCMFJWEFD. Global cancer statistics. CA Cancer J Clin. 2011 ; 61(2): 69-90.
18. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014; 23(5): 700-13.
19. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer. 2013.
20. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Epidemiology of gastric cancer: global trends, risk factors and prevention. Gastroenterology Review/Przegląd Gastroenterologiczny. 2018;: p. 80001.
21. Ang TL FK. Clinical epidemiology of gastric cancer. Singapore Med J. 2014; 55(12): 621-8.
22. Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F. Treatment of gastric cancer. World J Gastroenterol. 2014; 20: 1635-49.
23. Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, Ho J, Unverzagt S. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017; 8: p. CD004064.
24. Bilgin B, Sendur MA, Bülent Akıncı M, Şener Dede D, Yalçın B.. Targeting the PD-1 pathway: a new hope for gastrointestinal cancers. Curr Med Res Opin. 2017; 33: p. 749-59.
25. Bravo, L., García, L., Collazos, P., Carrascal, E., Ramírez, O., Cortés, A., Nuñez, M., & Millán, E. Reliable information for cancer control in Cali, Colombia. Colomb Med (Cali). 2018; ; 49(1): . 23-34.
26. L Laurén PA, Nevalainen TJ. Epidemiology of intestinal and diffuse types of gastric carcinoma. A time-trend study in Finland with comparison between studies from high- and low-risk areas. Cancer. 1993; 71: 2926–33.
27. Ikeda Y, Mori M, Kamakura T, Haraguchi Y, Saku M, Sugimachi K. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer. Br J Cancer. 1995; 72: 424–6.
28. Yu J, Zhao Q. The demographic characteristics of histological types of gastric cancer with gender, age, and tumor location. J Gastrointest Cancer. 2009; 40: p. 98–100.
29. Popiela T KJKPSM. Changing patterns of gastric carcinoma over the past two decades in a single institution: clinicopathological findings in 1557 patients. Scand J Gastroenterol. 2002; 37:. 561–7.
30. Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States 1973-2000: increase in the signet ring cell type. Arch Pathol Lab Med. 2004; 128: p. 765–70.
31. Lundegårdh G, Lindgren A, Rohul A, Nyrén O, Hansson LE, Bergström R, Adami HO. Intestinal and diffuse types of gastric cancer: secular trends in Sweden since 1951. Br J Cancer. 1991; 64: p. 1182–6.
32. Kaneko S, Yoshimura T.Time trend analysis of gastric cancer incidence in Japan by histological types 1975-1989. Br J Cancer. 2001; 84: 400–5.
33. FT B . WHO classification of tumours of the digestive system. Lyon: IARC. 2010; 3: 417.
34. Sipponen P, Correa P Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern: etiologic hypothesis. Gastric Cancer. 2002; 5(4): 213-9.
35. Camargo MC, Goto Y, Zabaleta J, Morgan DR, Correa P, Rabkin CS.. Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012; 21(1): 20-38.
36. Arnold M, Moore SP, Hassler S, Ellison-Loschmann L, Forman D, Bray F. The burden of stomach cancer in indigenous populations: a systematic review and global assessment. Gut. 2014; 63(1): 64-71.
37. Naess O, Strand BH, Smith GD. Childhood and adulthood socioeconomic position across 20 causes of death: a prospective cohort study of 800,000 Norwegian men and women. J Epidemiol Community Health. 2007; 61(11): 1004-9.
38. Nagel G, Linseisen J, Boshuizen HC, Pera G, Del Giudice G, Westert GP, Bueno-de-Mesquita HB, Allen NE, Key TJ, Numans ME, Peeters PH, Sieri S, Siman H, Berglund G, Hallmans G, Stenling R, Martinez C, Arriola L, Barricarte A, Chirlaque MD, Quiros JR, Vineis P, Masala G, Palli D, Panico S, Tumino R, Bingham S, Boeing H, Bergmann MM, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Olsen A, Tjonneland A, Trichopoulou A, Bamia C, Soukara S, Sabourin JC, Carneiro F, Slimani N, Jenab M, Norat T, Riboli E, González CA.. Socioeconomic position and the risk of gastric and oesophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Epidemiol. 2007 ; 36(1): 66-76.
39. Ghoshal UC, Chaturvedi R, Correa P. The enigma of Helicobacter pylori infection and gastric cancer. Indian J Gastroenterol. 2010; 29(3): 95-100
40. Ladeiras-Lopes R, Pereira AK, Nogueira A, Pinheiro-Torres T, Pinto I, Santos-Pereira R, Lunet N. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control. 2008; 19(7): 689-701.
41. Sadjadi A, Derakhshan MH, Yazdanbod A, Boreiri M, Parsaeian M, Babaei M, Alimohammadian M, Samadi F, Etemadi A, Pourfarzi F, Ahmadi E, Delavari A, Islami F, Farzadfar F, Sotoudeh M, Nikmanesh A, Alizadeh BZ, de Bock GH, Malekzadeh R.. Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fraction. Int J Cancer. 2014; 134: 181-8.
42. De Falco M, Lucariello A, Iaquinto S, Esposito V, Guerra G, De Luca A Molecular Mechanisms of Helicobacter pylori Pathogenesis. J Cell Physiol. 2015; 230(8): p. 1702-7.
43. Ge S, Feng X, Shen L, Wei Z, Zhu Q, Sun J. Association between Habitual Dietary Salt Intake and Risk of Gastric Cancer: A Systematic Review of Observational Studies. Gastroenterol Res Pract.. 2012; 2012: 808120.
44. Kim J, Park S, Nam BH.Gastric cancer and salt preference: a population-based cohort study in Korea. Am J Clin Nutr. 2010; 91(5):1289-93.
45. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Committee. EG. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 216; 27(suppl 5): v38-v49.
46. Zhang XY, Zhang PY, Aboul-Soud MA.From inflammation to gastric cancer: Role of Helicobacter pylori. Oncol Lett. 2017; 13(2): 543-8.
47. M. K. Epithelial-mesenchymal transition in gastric cancer (Review). Int J Oncol. 2005; 27(6): 1677-83.
48. Ferraz MA, Zabaglia LM, Pereira WN, Orcini WA, de Labio RW, Caleman Neto A, Wisnieski F, Calcagno DQ, Santos LC, Assumpção PP, Burbano RR, Artigiani R, Smith Mde A, Payão SL, Rasmussen LT. Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers. J Gastrointest Cancer. 2016; 47(1): 20-6.
49. Torabizadeh Z, Nosrati A, Sajadi Saravi SN, Yazdani Charati J, Janbabai G.. Evaluation of E-cadherin Expression in Gastric Cancer and Its Correlation with Clinicopathologic Parameters. Int J Hematol Oncol Stem Cell Res. 2017; 11(2): 158-64.
50. Huiping C, Kristjansdottir S, Jonasson JG, Magnusson J, Egilsson V, Ingvarsson S. Alterations of E-cadherin and beta-catenin in gastric cancer. BMC Cancer. 2001; 1:16.
51. Chiurillo MA. Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review. World J Exp Med. 2015; 5(2): p. 84-102.
52. Triantafyllou K PVETGPDVTGPIVILS. Eradication of Helicobacter pylori Infection Restores ki67, p53, and Cyclin D1 Immunoreactivity in the Human Gastric Epithelium. Clin Med Insights Gastroenterol. 2016; 9: 73-8.
53. Gao P, Zhou GY, Liu Y, Li JS, Zhen JH, Yuan YP. Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance. World J Gastroenterol. 2004; 10(20): 2936-9.
54. Kumari S, Puneet, Prasad SB, Yadav SS, Kumar M, Khanna A, Dixit VK, Nath G, Singh S, Narayan G. Cyclin D1 and cyclin E2 are differentially expressed in gastric cancer. Med Oncol. 2016; 33(5): 40.
55. Ida S, Watanabe M, Baba H. Chronic inflammation and gastrointestinal cancer. J Cancer Metastasis Treat. 2015; 1(3): 138-43.
56. Mahmoudzadeh Sagheb H, Heidari Z, Jahantigh M, Narouei M. Immunohistochemical Expression of p53 and Ki-67 Genes in Gastric Cancer and Precancerous Lesions in the Patients with Helicobacter pylori Infection. Gene Cell Tissue. 2016; 3(4): e41341.
57. Teh M, Tan, K.B, Seet BL, Yeoh KG. Study of p53 immunostaining in the gastric epithelium of cagA-positive and cagA-negative Helicobacter pylori gastritis. Cancer. 2002; 95(3): p. 499-505.
58. Shah MA, Khanin R, Tang L, Janjigian YY, Klimstra DS, Gerdes H, Kelsen DP. Molecular classification of gastric cancer: a new paradigm. Clin Cancer Res. 2011; 17(9): 2693-701.
59. Tan IB, Ivanova T, Lim KH, Ong CW, Deng N, Lee J, Tan SH, Wu J, Lee MH, Ooi CH, Rha SY, Wong WK, Boussioutas A, Yeoh KG, So J, Yong WP, Tsuburaya A, Grabsch H, Toh HC, Rozen S, Cheong JH, Noh SH, Wan WK, Ajani JA, Lee JS, Tellez MS, Tan P. Intrinsic Subtypes of Gastric Cancer, Based on Gene Expression Pattern, Predict Survival and Respond Differently to Chemotherapy. Gastroenterology. 2011; 141(2): e1-11.
60. Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S, Chua C, Feng Z, Guan YK, Ooi CH, Ivanova T, Zhang S, Lee M, Wu J, Ngo A, Manesh S, Tan E, Teh BT, So JB, Goh LK, Boussioutas A, Lim TK, Flotow H, Tan P, Rozen SG. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013; 145(3): 554-65.
61. Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, Siu HC, Deng S, Chu KM, Law S, Chan KH, Chan AS, Tsui WY, Ho SL, Chan AK, Man JL, Foglizzo V, Ng MK, Chan AS, Ching YP, Cheng GH, Xie T, Fernandez J, Li VS, Clevers H, Rejto PA, Mao M, Leung SY. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014; 46(6): 573-82.
62. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517): 202–9.
63. Li J, Zhang XH, Bei SH, Feng L. PD-1/PD-L1 antagonists in gastric cancer: Current studies and perspectives. World J Meta-Anal. 2019; 7(3): 101-9.
64. You W, Shang B, Sun J, Liu X, Su L, Jiang S. Mechanistic insight of predictive biomarkers for antitumor PD‑1/PD‑L1 blockade: A paradigm shift towards immunome evaluation (Review). Oncol Rep. 2020 Aug;44(2):424-437.
65. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372(26): 2509–20.
66. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357(6349): 409–13.
67. Derks S, Liao X, Chiaravalli AM, Xu X, Camargo MC, Solcia E, Sessa F, Fleitas T, Freeman GJ, Rodig SJ, Rabkin CS, Bass AJ. Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016; 7(22): 32925-32.
68. Sasaki S, Nishikawa J, Sakai K, Iizasa H, Yoshiyama H, Yanagihara M, Shuto T, Shimokuri K, Kanda T, Suehiro Y, Yamasaki T, Sakaida I. EBV-associated gastric cancer evades T-cell immunity by PD-1/PD-L1 interactions. Gastric Cancer. 2018; 22(3): 486-96.
69. Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, Zhong X, Li X, Qian H, Wang X. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. PLoS One. 2017; 12: e0182692.
70. Cho J, Chang YH, Heo YJ, Kim S, Kim NK, Park JO, Kang WK, Lee J, Kim KM. Four distinct immune microenvironment subtypes in gastric adenocarcinoma with special reference to microsatellite instability. ESMO Open. 2018; 3: e000326.
71. De Rosa S, Sahnane N, Tibiletti MG, Magnoli F, Vanoli A, Sessa F, Chiaravalli AM. EBV⁺ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8⁺ Intratumoral Lymphocytes. Cancers (Basel). 2018; 10:pii:E102.
72. Ma C, Patel K, Singhi AD, Ren B, Zhu B, Shaikh F, Sun W. Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability. Surg Pathol. 2016; 40: 1496-506.
73. Wang L, Zhang Q, Ni S, Tan C, Cai X, Huang D, Sheng W. Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status. Cancer Med. 2018; 7(6): 2612–20.
74. Eto S, Yoshikawa K, Nishi M, Higashijima J, Tokunaga T, Nakao T, Kashihara H, Takasu C, Iwata T, Shimada M. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer. 2016; 19(2): 466–71.
75. Kim JW, Nam KH, Ahn SH, Park DJ, Kim HH, Kim SH, Chang H, Lee JO, Kim YJ, Lee HS, Kim JH, Bang SM, Lee JS, Lee KW. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016; 19(1): 42–52.
76. Li Z, Lai Y, Sun L, Zhang X, Liu R, Feng G, Zhou L, Jia L, Huang X, Kang Q, Lin D, Gao J, Shen L.. PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer. Hum Pathol. 2016; 55: 182–9.
77. Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, Yang S, Duncan M, Ahuja N, Taube JM, Anders RA, Kelly RJ. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017; 66(5): 794–801.
78. Pereira MA, Ramos MFKP, Faraj SF, Dias AR, Yagi OK, Zilberstein B, Cecconello I, Alves VAF, de Mello ES, Ribeiro U Jr. Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer. J Surg Oncol. 2018; 117(5): 829-39.
79. Xing X, Guo J, Ding G, Li B, Dong B, Feng Q, Li S, Zhang J, Ying X, Cheng X, Guo T, Du H, Hu Y, Zhou T, Wang X, Li L, Li Q, Xie M, Li L, Gao X, Shan F, Li Z, Jia S, Wen X, Wang J, Ji J. Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients. Oncoimmunology. 2018; 7(3): e1356144.
80. Kim KH, Choi SJ, Choi YI, Kim L, Park IS, Han JY, Kim JM, Chu YC. In-house Manual Construction of High-Density and High-Quality Tissue Microarrays by Using Homemade Recipient Agarose-Paraffin Blocks. Korean J Pathol. 2013;47(3):238-44.
81. Koh J, Lee KW, Nam SK, Seo AN, Kim JW, Kim JW, Park DJ, Kim HH, Kim WH, Lee HS. Development and Validation of an Easy-to-Implement, Practical Algorithm for the Identification of Molecular Subtypes of Gastric Cancer: Prognostic and Therapeutic Implications. Oncologist. 2019;24(12):e1321-e1330.
82. Ramos MFKP, Pereira MA, de Mello ES, Cirqueira CDS, Zilberstein B, Alves VAF, Ribeiro-Junior U, Cecconello I. Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery. World J Clin Oncol. 2021;12(8):688-701.
83. Nshizirungu JP, Bennis S, Mellouki I, Sekal M, Benajah DA, Lahmidani N, El Bouhaddouti H, Ibn Majdoub K, Ibrahimi SA, Celeiro SP, Viana-Pereira M, Munari FF, Ribeiro GG, Duval V, Santana I, Reis RM. Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients. Dis Markers. 2021;2021:9980410.
84. Vidal-Realpe A, Dueñas-Cuellar RA, Niño-Castaño VE, Mora-Obando DL, Arias-Agudelo JJ, Bolaños HJ. Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia. Rev Gastroenterol Mex (Engl Ed). 2022:S2255-534X(22)00066-4.
85. Yoon JY, Sy K, Brezden-Masley C, Streutker CJ. Histo- and immunohistochemistry-based estimation of the TCGA and ACRG molecular subtypes for gastric carcinoma and their prognostic significance: A single-institution study. PLoS ONE. 2019. 14(12): e0224812.
86. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018;24(9):1449–58.
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dc.rights.license.spa.fl_str_mv Reconocimiento 4.0 Internacional
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spelling Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Franco Tavera, Oscar Andresb0769ea91108bb8593faf87c76eeca83Gallo Gomez, Yeinson Nabord06e2783151c5fb788e7376430d86c7dAnatomopatologíaGallo Gomez, Nabor (0000-0003-3795-4660)Gallo Gomez, Yeinson Nabor (0001600796)2023-01-23T15:47:14Z2023-01-23T15:47:14Z2021https://repositorio.unal.edu.co/handle/unal/83061Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, fotografías, graficasIntroducción: El cáncer gástrico sigue siendo una de las neoplasias malignas más comunes y letales en todo el mundo. Una mejor comprensión de los diferentes mecanismos moleculares del cáncer gástrico podría llevar a la individualización de blancos terapéuticos y garantizar su eficacia. De ahí la necesidad de uso de métodos simplificados para la subtipificación de este cáncer extrapolando la clasificación del AGC y el GAIC. Objetivo: Evaluar los subgrupos moleculares del carcinoma gástrico usando métodos de IHQ e HIS, basados en un panel de 4 marcadores (MLH1, E-cadherina, P53 y ARNm del virus de Epstein-Barr) y su relación con la expresión de PD L1 en una población colombiana. Metodología: Uso de microarreglos de tejido para la evaluación mediante IHQ e HIS en un grupo de muestras embebidas en parafina y clasificar estos según la clasificación del AGC, el GAIC y la clasificación integrada. Resultados: Se encontraron un total de 25 pacientes, que se distribuyeron según cada clasificación de la siguiente manera: clasificación integral: G1: 8 %, G2: 12 %, G3: 20 %, G4: 36 % y G5: 24 %; clasificación AGC: EBV: 8 %, MSI: 12 %, GS: 20 % y CIN 60 %; y clasificación GAIC: MSI: 12 %, MSS / EMT: 20 %, MSS/TP53-: 36 % y MSS/TP53+: 32 %. Se identifico 8 % de los casos tenían un puntaje PPC≥1 para PD-L1. Conclusión: Los algoritmos de subtipificación de cáncer gástrico son reproducibles y asequibles, permitiendo reproducir las clasificaciones AGC, GAIC e integradas de cáncer gástrico, utilizando técnicas disponibles en el diagnóstico de rutina. (Texto tomado de la fuente)Introduction: Gastric cancer remains one of the most common and lethal malignancies worldwide. A better understanding of the different molecular mechanisms of gastric cancer could help identify therapeutic targets and guarantee their efficacy. Hence the need to use simplified methods for the subtyping of this cancer, extrapolating the AGC and GAIC classification. Objective: The molecular subgroups of gastric carcinoma will be evaluated using IHC and HIS methods, based on a panel of 4 markers (MLH1, E-cadherin, P53 and Epstein-Barr virus mRNA) and their relationship with PD L1 expression. in a Colombian population. Methodology: Use of tissue microarrays for evaluation by means of IHC and HIS in a group of samples embedded in paraffin and classifying these according to the AGC, GAIC and integrated classifications. Results: A total of 25 patients were found, who were distributed according to each classification as follows: comprehensive classification: G1: 8 %, G2: 12 %, G3: 20 %, G4: 36 % and G5: 24 %; AGC classification: EBV: 8 %, MSI: 12 %, GS: 20 % and CIN 60 %; and GAIC classification: MSI: 12 %, MSS/EMT: 20 %, MSS/TP53-: 36 % and MSS/TP53+: 32 %. 8 % of cases having a PPC score≥1 for PD-L1 are identified. Conclusion: Gastric cancer subtyping algorithms are reproducible and affordable, reproducing AGC, GAIC, and integrated classifications of gastric cancer, using techniques available in routine diagnosisEspecialidades MédicasEspecialista en Patología Anatómica y ClínicaTumores Sólidosxii, 75 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Especialidad en Patología Anatómica y ClínicaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y saludARN MensajeroHerpesvirus Humano 4Núcleo FamiliarMétodosFibra de LanaNeoplasias gástricasPatología molecularInmunohistoquímicaHibridación fluorescente in situStomach NeoplasmsMolecular PathologyImmunohistochemistryIn Situ Hybridization, FluorescenceEvaluación de la clasificación molecular del cáncer gástrico por inmunohistoquímica e hibridación in situ y su relación con la expresión de PD-L1 en pacientes del Hospital Universitario Nacional entre el 2016 - 2021Evaluation of the molecular classification of gastric cancer by immunohistochemistry and in situ hybridization and its relationship with the expression of PD-L1 and patients of the Hospital Universitario Nacional between 2016 and 2021Trabajo de grado - Especialidad Médicainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TM1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249.2. Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018; 10:239-48.3. Sun Y, Yu W, Guan W, Cai L, Qiao M, Zheng L, Jiang R, Wang R, Wang L. Integrated assessment of PD-L1 expression and molecular classification facilitates therapy selection and prognosis prediction in gastric cancer. Cancer Manag Res. 2019; 11: 6397-410.4. Lahmidani N, et al. Update on Gastric Cancer Epidemiology and Risk Factors. Journal of Cancer Therapy. 2018; 9:242-54.5. Network CGAR. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517):202-9.6. Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015; 21(5):449-56.7. Birkman EM, Mansuri N, Kurki S, Ålgars A, Lintunen M, Ristamäki R, Sundström J, Carpén O. Gastric cancer: immunohistochemical classification of molecular subtypes and their association with clinicopathological characteristics. Virchows Arch. 2018; 472(3): p. 369-82.8. R Oliveros, RE Pinilla, H Facundo-Navia, R Sánchez-Pedraza. Cáncer gástrico: una enfermedad prevenible. Estrategias para intervención en la historia natural. Rev. colomb. Gastroenterol. 2019; 34(2): 177-89.9. Díaz Del Arco C, Estrada Muñoz L, Molina Roldán E, Cerón Nieto MÁ, Ortega Medina L, García Gómez de Las Heras S, Fernández Aceñero MJ. Immunohistochemical classification of gastric cancer based on new molecular biomarkers: a potential predictor of survival. Virchows Arch. 2018; 473(3): p. 687-95.10. Kim HS, Shin SJ, Beom SH, Jung M, Choi YY, Son T, Kim HI, Cheong JH, Hyung WJ, Noh SH, Chung H, Park JC, Shin SK, Lee SK, Lee YC, Koom WS, Lim JS, Chung HC, Rha SY, Kim H. Comprehensive expression profiles of gastric cancer molecular subtypes by immunohistochemistry: implications for individualized therapy. Oncotarget. 2016; 7(28): 44608-20.11. Ahn S, Lee SJ, Kim Y, Kim A, Shin N, Choi KU, Lee CH, Huh GY, Kim KM, Setia N, Lauwers GY, Park DY.. High-throughput Protein and mRNA Expression-based Classification of Gastric Cancers Can Identify Clinically Distinct Subtypes, Concordant With Recent Molecular Classifications. 2017; 41(1): 106-15.12. Setia N, Agoston AT, Han HS, Mullen JT, Duda DG, Clark JW, Deshpande V, Mino-Kenudson M, Srivastava A, Lennerz JK, Hong TS, Kwak EL, Lauwers GYA protein and mRNA expression-based classification of gastric cancer. Mod Pathol. 2016; 29(7): 772-84.13. Gonzalez RS, Messing S, Tu X, McMahon LA, Whitney-Miller CL. Immunohistochemistry as a surrogate for molecular subtyping of gastric adenocarcinoma. Hum Pathol. 2016; 56: 16-21.14. Park CK, Park JS, Kim HS, Rha SY, Hyung WJ, Cheong JH, Noh SH, Lee SK, Lee YC, Huh YM, Kim H. Receptor tyrosine kinase amplified gastric cancer: Receptor tyrosine kinase amplified gastric cancer: Clinicopathologic characteristics and proposed screening algorithm. Oncotarget. 2016; 7(44):72099-112.15. Sun Y,Yu W, Guan W, Qiao M, Zheng L,Jiang R,. Wang R, Wang L.Assessment of molecular classification of gastric cancer by immunohistochemistry and in situ hybridization: A validation study in the Chinese population. Ann Oncol. 2018; 29(9): mdy432.018.16. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010; 127(12): p. 2893-917.17. Jemal A BFCMFJWEFD. Global cancer statistics. CA Cancer J Clin. 2011 ; 61(2): 69-90.18. Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer Epidemiol Biomarkers Prev. 2014; 23(5): 700-13.19. Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer. 2013.20. Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Epidemiology of gastric cancer: global trends, risk factors and prevention. Gastroenterology Review/Przegląd Gastroenterologiczny. 2018;: p. 80001.21. Ang TL FK. Clinical epidemiology of gastric cancer. Singapore Med J. 2014; 55(12): 621-8.22. Orditura M, Galizia G, Sforza V, Gambardella V, Fabozzi A, Laterza MM, Andreozzi F, Ventriglia J, Savastano B, Mabilia A, Lieto E, Ciardiello F, De Vita F. Treatment of gastric cancer. World J Gastroenterol. 2014; 20: 1635-49.23. Wagner AD, Syn NL, Moehler M, Grothe W, Yong WP, Tai BC, Ho J, Unverzagt S. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev. 2017; 8: p. CD004064.24. Bilgin B, Sendur MA, Bülent Akıncı M, Şener Dede D, Yalçın B.. Targeting the PD-1 pathway: a new hope for gastrointestinal cancers. Curr Med Res Opin. 2017; 33: p. 749-59.25. Bravo, L., García, L., Collazos, P., Carrascal, E., Ramírez, O., Cortés, A., Nuñez, M., & Millán, E. Reliable information for cancer control in Cali, Colombia. Colomb Med (Cali). 2018; ; 49(1): . 23-34.26. L Laurén PA, Nevalainen TJ. Epidemiology of intestinal and diffuse types of gastric carcinoma. A time-trend study in Finland with comparison between studies from high- and low-risk areas. Cancer. 1993; 71: 2926–33.27. Ikeda Y, Mori M, Kamakura T, Haraguchi Y, Saku M, Sugimachi K. Improvements in diagnosis have changed the incidence of histological types in advanced gastric cancer. Br J Cancer. 1995; 72: 424–6.28. Yu J, Zhao Q. The demographic characteristics of histological types of gastric cancer with gender, age, and tumor location. J Gastrointest Cancer. 2009; 40: p. 98–100.29. Popiela T KJKPSM. Changing patterns of gastric carcinoma over the past two decades in a single institution: clinicopathological findings in 1557 patients. Scand J Gastroenterol. 2002; 37:. 561–7.30. Henson DE, Dittus C, Younes M, Nguyen H, Albores-Saavedra J. Differential trends in the intestinal and diffuse types of gastric carcinoma in the United States 1973-2000: increase in the signet ring cell type. Arch Pathol Lab Med. 2004; 128: p. 765–70.31. Lundegårdh G, Lindgren A, Rohul A, Nyrén O, Hansson LE, Bergström R, Adami HO. Intestinal and diffuse types of gastric cancer: secular trends in Sweden since 1951. Br J Cancer. 1991; 64: p. 1182–6.32. Kaneko S, Yoshimura T.Time trend analysis of gastric cancer incidence in Japan by histological types 1975-1989. Br J Cancer. 2001; 84: 400–5.33. FT B . WHO classification of tumours of the digestive system. Lyon: IARC. 2010; 3: 417.34. Sipponen P, Correa P Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern: etiologic hypothesis. Gastric Cancer. 2002; 5(4): 213-9.35. Camargo MC, Goto Y, Zabaleta J, Morgan DR, Correa P, Rabkin CS.. Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2012; 21(1): 20-38.36. Arnold M, Moore SP, Hassler S, Ellison-Loschmann L, Forman D, Bray F. The burden of stomach cancer in indigenous populations: a systematic review and global assessment. Gut. 2014; 63(1): 64-71.37. Naess O, Strand BH, Smith GD. Childhood and adulthood socioeconomic position across 20 causes of death: a prospective cohort study of 800,000 Norwegian men and women. J Epidemiol Community Health. 2007; 61(11): 1004-9.38. Nagel G, Linseisen J, Boshuizen HC, Pera G, Del Giudice G, Westert GP, Bueno-de-Mesquita HB, Allen NE, Key TJ, Numans ME, Peeters PH, Sieri S, Siman H, Berglund G, Hallmans G, Stenling R, Martinez C, Arriola L, Barricarte A, Chirlaque MD, Quiros JR, Vineis P, Masala G, Palli D, Panico S, Tumino R, Bingham S, Boeing H, Bergmann MM, Overvad K, Boutron-Ruault MC, Clavel-Chapelon F, Olsen A, Tjonneland A, Trichopoulou A, Bamia C, Soukara S, Sabourin JC, Carneiro F, Slimani N, Jenab M, Norat T, Riboli E, González CA.. Socioeconomic position and the risk of gastric and oesophageal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Int J Epidemiol. 2007 ; 36(1): 66-76.39. Ghoshal UC, Chaturvedi R, Correa P. The enigma of Helicobacter pylori infection and gastric cancer. Indian J Gastroenterol. 2010; 29(3): 95-10040. Ladeiras-Lopes R, Pereira AK, Nogueira A, Pinheiro-Torres T, Pinto I, Santos-Pereira R, Lunet N. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes Control. 2008; 19(7): 689-701.41. Sadjadi A, Derakhshan MH, Yazdanbod A, Boreiri M, Parsaeian M, Babaei M, Alimohammadian M, Samadi F, Etemadi A, Pourfarzi F, Ahmadi E, Delavari A, Islami F, Farzadfar F, Sotoudeh M, Nikmanesh A, Alizadeh BZ, de Bock GH, Malekzadeh R.. Neglected role of hookah and opium in gastric carcinogenesis: a cohort study on risk factors and attributable fraction. Int J Cancer. 2014; 134: 181-8.42. De Falco M, Lucariello A, Iaquinto S, Esposito V, Guerra G, De Luca A Molecular Mechanisms of Helicobacter pylori Pathogenesis. J Cell Physiol. 2015; 230(8): p. 1702-7.43. Ge S, Feng X, Shen L, Wei Z, Zhu Q, Sun J. Association between Habitual Dietary Salt Intake and Risk of Gastric Cancer: A Systematic Review of Observational Studies. Gastroenterol Res Pract.. 2012; 2012: 808120.44. Kim J, Park S, Nam BH.Gastric cancer and salt preference: a population-based cohort study in Korea. Am J Clin Nutr. 2010; 91(5):1289-93.45. Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D. Committee. EG. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 216; 27(suppl 5): v38-v49.46. Zhang XY, Zhang PY, Aboul-Soud MA.From inflammation to gastric cancer: Role of Helicobacter pylori. Oncol Lett. 2017; 13(2): 543-8.47. M. K. Epithelial-mesenchymal transition in gastric cancer (Review). Int J Oncol. 2005; 27(6): 1677-83.48. Ferraz MA, Zabaglia LM, Pereira WN, Orcini WA, de Labio RW, Caleman Neto A, Wisnieski F, Calcagno DQ, Santos LC, Assumpção PP, Burbano RR, Artigiani R, Smith Mde A, Payão SL, Rasmussen LT. Downregulated Expression of E-cadherin and TP53 in Patients with Gastric Diseases: the Involvement of H. pylori Infection and Its Virulence Markers. J Gastrointest Cancer. 2016; 47(1): 20-6.49. Torabizadeh Z, Nosrati A, Sajadi Saravi SN, Yazdani Charati J, Janbabai G.. Evaluation of E-cadherin Expression in Gastric Cancer and Its Correlation with Clinicopathologic Parameters. Int J Hematol Oncol Stem Cell Res. 2017; 11(2): 158-64.50. Huiping C, Kristjansdottir S, Jonasson JG, Magnusson J, Egilsson V, Ingvarsson S. Alterations of E-cadherin and beta-catenin in gastric cancer. BMC Cancer. 2001; 1:16.51. Chiurillo MA. Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review. World J Exp Med. 2015; 5(2): p. 84-102.52. Triantafyllou K PVETGPDVTGPIVILS. Eradication of Helicobacter pylori Infection Restores ki67, p53, and Cyclin D1 Immunoreactivity in the Human Gastric Epithelium. Clin Med Insights Gastroenterol. 2016; 9: 73-8.53. Gao P, Zhou GY, Liu Y, Li JS, Zhen JH, Yuan YP. Alteration of cyclin D1 in gastric carcinoma and its clinicopathologic significance. World J Gastroenterol. 2004; 10(20): 2936-9.54. Kumari S, Puneet, Prasad SB, Yadav SS, Kumar M, Khanna A, Dixit VK, Nath G, Singh S, Narayan G. Cyclin D1 and cyclin E2 are differentially expressed in gastric cancer. Med Oncol. 2016; 33(5): 40.55. Ida S, Watanabe M, Baba H. Chronic inflammation and gastrointestinal cancer. J Cancer Metastasis Treat. 2015; 1(3): 138-43.56. Mahmoudzadeh Sagheb H, Heidari Z, Jahantigh M, Narouei M. Immunohistochemical Expression of p53 and Ki-67 Genes in Gastric Cancer and Precancerous Lesions in the Patients with Helicobacter pylori Infection. Gene Cell Tissue. 2016; 3(4): e41341.57. Teh M, Tan, K.B, Seet BL, Yeoh KG. Study of p53 immunostaining in the gastric epithelium of cagA-positive and cagA-negative Helicobacter pylori gastritis. Cancer. 2002; 95(3): p. 499-505.58. Shah MA, Khanin R, Tang L, Janjigian YY, Klimstra DS, Gerdes H, Kelsen DP. Molecular classification of gastric cancer: a new paradigm. Clin Cancer Res. 2011; 17(9): 2693-701.59. Tan IB, Ivanova T, Lim KH, Ong CW, Deng N, Lee J, Tan SH, Wu J, Lee MH, Ooi CH, Rha SY, Wong WK, Boussioutas A, Yeoh KG, So J, Yong WP, Tsuburaya A, Grabsch H, Toh HC, Rozen S, Cheong JH, Noh SH, Wan WK, Ajani JA, Lee JS, Tellez MS, Tan P. Intrinsic Subtypes of Gastric Cancer, Based on Gene Expression Pattern, Predict Survival and Respond Differently to Chemotherapy. Gastroenterology. 2011; 141(2): e1-11.60. Lei Z, Tan IB, Das K, Deng N, Zouridis H, Pattison S, Chua C, Feng Z, Guan YK, Ooi CH, Ivanova T, Zhang S, Lee M, Wu J, Ngo A, Manesh S, Tan E, Teh BT, So JB, Goh LK, Boussioutas A, Lim TK, Flotow H, Tan P, Rozen SG. Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil. Gastroenterology. 2013; 145(3): 554-65.61. Wang K, Yuen ST, Xu J, Lee SP, Yan HH, Shi ST, Siu HC, Deng S, Chu KM, Law S, Chan KH, Chan AS, Tsui WY, Ho SL, Chan AK, Man JL, Foglizzo V, Ng MK, Chan AS, Ching YP, Cheng GH, Xie T, Fernandez J, Li VS, Clevers H, Rejto PA, Mao M, Leung SY. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet. 2014; 46(6): 573-82.62. Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517): 202–9.63. Li J, Zhang XH, Bei SH, Feng L. PD-1/PD-L1 antagonists in gastric cancer: Current studies and perspectives. World J Meta-Anal. 2019; 7(3): 101-9.64. You W, Shang B, Sun J, Liu X, Su L, Jiang S. Mechanistic insight of predictive biomarkers for antitumor PD‑1/PD‑L1 blockade: A paradigm shift towards immunome evaluation (Review). Oncol Rep. 2020 Aug;44(2):424-437.65. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015; 372(26): 2509–20.66. Le DT, Durham JN, Smith KN, Wang H, Bartlett BR, Aulakh LK, Lu S, Kemberling H, Wilt C, Luber BS, Wong F, Azad NS, Rucki AA, Laheru D, Donehower R, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Greten TF, Duffy AG, Ciombor KK, Eyring AD, Lam BH, Joe A, Kang SP, Holdhoff M, Danilova L, Cope L, Meyer C, Zhou S, Goldberg RM, Armstrong DK, Bever KM, Fader AN, Taube J, Housseau F, Spetzler D, Xiao N, Pardoll DM, Papadopoulos N, Kinzler KW, Eshleman JR, Vogelstein B, Anders RA, Diaz LA Jr. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science. 2017; 357(6349): 409–13.67. Derks S, Liao X, Chiaravalli AM, Xu X, Camargo MC, Solcia E, Sessa F, Fleitas T, Freeman GJ, Rodig SJ, Rabkin CS, Bass AJ. Abundant PD-L1 expression in Epstein-Barr Virus-infected gastric cancers. Oncotarget. 2016; 7(22): 32925-32.68. Sasaki S, Nishikawa J, Sakai K, Iizasa H, Yoshiyama H, Yanagihara M, Shuto T, Shimokuri K, Kanda T, Suehiro Y, Yamasaki T, Sakaida I. EBV-associated gastric cancer evades T-cell immunity by PD-1/PD-L1 interactions. Gastric Cancer. 2018; 22(3): 486-96.69. Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, Zhong X, Li X, Qian H, Wang X. PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis. PLoS One. 2017; 12: e0182692.70. Cho J, Chang YH, Heo YJ, Kim S, Kim NK, Park JO, Kang WK, Lee J, Kim KM. Four distinct immune microenvironment subtypes in gastric adenocarcinoma with special reference to microsatellite instability. ESMO Open. 2018; 3: e000326.71. De Rosa S, Sahnane N, Tibiletti MG, Magnoli F, Vanoli A, Sessa F, Chiaravalli AM. EBV⁺ and MSI Gastric Cancers Harbor High PD-L1/PD-1 Expression and High CD8⁺ Intratumoral Lymphocytes. Cancers (Basel). 2018; 10:pii:E102.72. Ma C, Patel K, Singhi AD, Ren B, Zhu B, Shaikh F, Sun W. Programmed Death-Ligand 1 Expression Is Common in Gastric Cancer Associated With Epstein-Barr Virus or Microsatellite Instability. Surg Pathol. 2016; 40: 1496-506.73. Wang L, Zhang Q, Ni S, Tan C, Cai X, Huang D, Sheng W. Programmed death-ligand 1 expression in gastric cancer: correlation with mismatch repair deficiency and HER2-negative status. Cancer Med. 2018; 7(6): 2612–20.74. Eto S, Yoshikawa K, Nishi M, Higashijima J, Tokunaga T, Nakao T, Kashihara H, Takasu C, Iwata T, Shimada M. Programmed cell death protein 1 expression is an independent prognostic factor in gastric cancer after curative resection. Gastric Cancer. 2016; 19(2): 466–71.75. Kim JW, Nam KH, Ahn SH, Park DJ, Kim HH, Kim SH, Chang H, Lee JO, Kim YJ, Lee HS, Kim JH, Bang SM, Lee JS, Lee KW. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016; 19(1): 42–52.76. Li Z, Lai Y, Sun L, Zhang X, Liu R, Feng G, Zhou L, Jia L, Huang X, Kang Q, Lin D, Gao J, Shen L.. PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer. Hum Pathol. 2016; 55: 182–9.77. Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, Yang S, Duncan M, Ahuja N, Taube JM, Anders RA, Kelly RJ. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017; 66(5): 794–801.78. Pereira MA, Ramos MFKP, Faraj SF, Dias AR, Yagi OK, Zilberstein B, Cecconello I, Alves VAF, de Mello ES, Ribeiro U Jr. Clinicopathological and prognostic features of Epstein-Barr virus infection, microsatellite instability, and PD-L1 expression in gastric cancer. J Surg Oncol. 2018; 117(5): 829-39.79. Xing X, Guo J, Ding G, Li B, Dong B, Feng Q, Li S, Zhang J, Ying X, Cheng X, Guo T, Du H, Hu Y, Zhou T, Wang X, Li L, Li Q, Xie M, Li L, Gao X, Shan F, Li Z, Jia S, Wen X, Wang J, Ji J. Analysis of PD1, PDL1, PDL2 expression and T cells infiltration in 1014 gastric cancer patients. Oncoimmunology. 2018; 7(3): e1356144.80. Kim KH, Choi SJ, Choi YI, Kim L, Park IS, Han JY, Kim JM, Chu YC. In-house Manual Construction of High-Density and High-Quality Tissue Microarrays by Using Homemade Recipient Agarose-Paraffin Blocks. Korean J Pathol. 2013;47(3):238-44.81. Koh J, Lee KW, Nam SK, Seo AN, Kim JW, Kim JW, Park DJ, Kim HH, Kim WH, Lee HS. Development and Validation of an Easy-to-Implement, Practical Algorithm for the Identification of Molecular Subtypes of Gastric Cancer: Prognostic and Therapeutic Implications. Oncologist. 2019;24(12):e1321-e1330.82. Ramos MFKP, Pereira MA, de Mello ES, Cirqueira CDS, Zilberstein B, Alves VAF, Ribeiro-Junior U, Cecconello I. Gastric cancer molecular classification based on immunohistochemistry and in situ hybridization: Analysis in western patients after curative-intent surgery. World J Clin Oncol. 2021;12(8):688-701.83. Nshizirungu JP, Bennis S, Mellouki I, Sekal M, Benajah DA, Lahmidani N, El Bouhaddouti H, Ibn Majdoub K, Ibrahimi SA, Celeiro SP, Viana-Pereira M, Munari FF, Ribeiro GG, Duval V, Santana I, Reis RM. Reproduction of the Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG) Gastric Cancer Molecular Classifications and Their Association with Clinicopathological Characteristics and Overall Survival in Moroccan Patients. Dis Markers. 2021;2021:9980410.84. Vidal-Realpe A, Dueñas-Cuellar RA, Niño-Castaño VE, Mora-Obando DL, Arias-Agudelo JJ, Bolaños HJ. Clinical and pathologic characteristics of gastric adenocarcinoma associated with Epstein-Barr virus in a region with a high incidence of gastric cancer in Colombia. Rev Gastroenterol Mex (Engl Ed). 2022:S2255-534X(22)00066-4.85. Yoon JY, Sy K, Brezden-Masley C, Streutker CJ. Histo- and immunohistochemistry-based estimation of the TCGA and ACRG molecular subtypes for gastric carcinoma and their prognostic significance: A single-institution study. PLoS ONE. 2019. 14(12): e0224812.86. Kim ST, Cristescu R, Bass AJ, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018;24(9):1449–58.BibliotecariosEstudiantesInvestigadoresMaestrosPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/83061/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINAL1088293037.2023.pdf1088293037.2023.pdfTrabajo de grado de Especialización en patología anatómica y clínicaapplication/pdf2748625https://repositorio.unal.edu.co/bitstream/unal/83061/2/1088293037.2023.pdf730a10437b0d29be55abb72a169b7a60MD52unal/83061oai:repositorio.unal.edu.co:unal/830612023-01-23 10:48:36.881Repositorio Institucional Universidad Nacional de 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