Molecular profile of gastric adenocarcinoma and the gastroesophageal junction
DOI:
https://doi.org/10.31837/cir.urug/10.1.9Keywords:
gastric cancer, PD-L1, Her2/neu, molecular characterization, microsatellite instability, UruguayAbstract
Gastric cancer is one of the most common malignant tumors of the digestive tract. In our setting, it generally presents at advanced stages. In these patients, advances in histopathological and molecular characterization have led to the implementation of targeted therapies. The combination with chemotherapy has demonstrated a significant increase in survival in patients with disseminated disease.
Objective: To perform an epidemiological, clinical, pathological, and molecular description of gastric and gastroesophageal junction tumors in a retrospective cohort from January 1, 2019, to October 31, 2024, at the Hospital de Clínicas, Montevideo, Uruguay.
Methodology: A descriptive, observational, and retrospective study was conducted over a 5-year period. Data were collected from all patients diagnosed and treated for gastric cancer at the Hospital de Clínicas Dr. Manuel Quíntela, whose records were archived in the Department of Pathology.
Results: A sample of 59 patients was obtained. PD-L1 was analyzed in 26 of them, with 10 positive and 16 negative results. Her2/neu expression was obtained in 49 patients, with 28 having a score of 0, 4 Her2/neu +, 9 Her2/neu ++, and 8 Her2/neu +++.
Microsatellite instability (MSI) was analyzed in 34 patients; 10 presented with MSI-H/dMMR and 24 with a low probability of MSI.
Conclusions: Molecular and epidemiological characterization of patients with gastric adenocarcinoma and gastroesophageal junction cancer was achieved. This is the first study in Uruguay to molecularly characterize these tumors in order to develop targeted cancer therapies for each molecular subtype (onco-specific).
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References
1.Lauwers G, Kumarasinghe P, Gastric cancer: Pathology and molecular pathogenesis. UpToDate. 2024.
2.Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, et. al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590). Lancet. 2021;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4
3.Luchini C, Bibeau F, Ligtenberg MJL, Singh N, Nottegar A, Bosse T, et. al. ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019;30(8):1232-43. doi: 10.1093/annonc/mdz116.
4.Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et. al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517):202-9. doi: 10.1038/nature13480
5.Chia NY, Tan P. Molecular classification of gastric cancer. Ann Oncol. 2016; 27(5):763-9. doi: 10.1093/annonc/mdw040
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. doi: 10.1038/nm.3850
7.Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, et. al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from KEYNOTE-158. Ann Oncol. 2022;33(9):929-38. doi: 10.1016/j.annonc.2022.05.519
8.Polom K, Marano L, Marrelli D, De Luca R, Roviello G, Savelli V, et. al. Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer. Br J Surg. 2018;105(3):159-167. doi: 10.1002/bjs.10663.
9.Castro MT, García AB, Arencibia AC, Martín-Arranz MD. Actualización en cáncer gástrico. Med - Programa Form Médica Contin Acreditado. 2024;14(3):128-36.
10.Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, et. al. Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric/GEJ adenocarcinoma: KEYNOTE-811. Lancet. 2023;402(10418):2197-208.
11.Lian J, Zhang G, Zhang Y, Liu H, Zhang J, Nan, P, et. al. PD-L1 and HER2 expression in gastric adenocarcinoma and their prognostic significance. Dig Liver Dis. 2022;54(10):1419-27. doi: 10.1016/j.dld.2022.01.128
12.Moran D, Maurus D, Rohde C, Arozullah A. Prevalence of CLDN18.2, HER2 and PD-L1 in gastric cancer samples. Ann Oncol. 2018;29(8)viii32. doi: 10.1093/annonc/mdy269.101
13.Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, et. al. Trastuzumab deruxtecan in previously treated HER2 -positive gastric cancer. N Engl J Med. 2020;382(25): 2419-2430. Doi: 10.1056/NEJMoa2004413
14.Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, et. al. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024;42(17):2012-2020. doi: 10.1200/JCO.23.01601
15. Rha SY, Oh DY, Yañez P, Bai Y, Ryu MH, Lee J, et. al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2023;24(11):1181-1195. doi: 10.1016/S1470-2045(23)00515-6.
16.Ajani JA, D’Amico TA, Bentrem DJ, Corvera CU, Das P, Enzinger PC, et. al. Gastric Cancer, Version 2.2025, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2025;23(5):169-191. doi: 10.6004/jnccn.2025.0022.
17. Lordick F, Carneiro F, Cascinu S, Fleitas T, Haustermans K, Piessen G, et. al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(10):1005-1020
18.Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Haller DG, et. al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001;345(10):725-30. doi: 10.1056/NEJMoa010187.
19.Shitara K, Lordick F, Bang YJ, Enzinger P, Ilson D, Shah MA, et. al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2023;401(10389):1655-1668. doi: 10.1016/S0140-6736(23)00620-7
20.Shah MA, Shitara Ka, Ajani JA, Bang YJ, Enzinger P, Ilson D, et. al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial. Nat Med. 2023;29(8):2133-2141. doi: 10.1038/s41591-023-02465-7
21.Comisión Honoraria de Lucha contra el Cáncer (Uruguay). Informes/recursos institucionales (sitio oficial). Montevideo: 2026.
22.Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, et. al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022;23(2):234-247. doi: 10.1016/S1470-2045(21)00692-6
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