Clinical, Endoscopic, and Histopathological Features of HER2 Expression and Two-Year Survival in Gastric Adenocarcinoma
), Marcellus Simadibrata(2), Nur Rahadiani(3), Ikhwan Rinaldi(4), Ruswhandi -(5), Edi Mulyana(6), Lianda Siregar(7),
(1) Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
(2) Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
(3) Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
(4) Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia
(5) Division of Gastroenterology and Hepatology, Gatot Soebroto Central Army Hospital
(6) Division of Gastroenterology and Hepatology, Fatmawati Central Hospital
(7) Division of Gastroentero Hepatology, Darmais National Cancer Hospital
Corresponding Author
Abstract
Background: HER2 is a proto-oncogene and therapeutic target in advanced gastric adenocarcinoma. Reports on its association with clinicopathological features and prognosis remain inconsistent. This study aimed to evaluate the relationship of clinical, endoscopic, and histopathological features with HER2 expression and its impact on two-year survival.
Methods: A retrospective cohort study was conducted among patients ≥18 years with newly diagnosed gastric adenocarcinoma at four hospitals in Jakarta (2015–2019). Eligible cases had complete records and paraffin blocks. HER2 was assessed by immunohistochemistry and CISH using ToGA criteria. Chi-square/Fisher’s tests evaluated associations, while survival was analysed with Kaplan-Meier and Cox regression.
Results: Among 122 patients, 15 (12.3%) were HER2-positive. More frequent expression was observed in liver metastases than in non-liver metastases (17.6% vs. 10.2%), in Borrmann type I/II than in Borrmann type III/IV (16.1% vs. 9.1%), in moderately rather than in poorly differentiated tumors (14.3% vs. 11%), and in intestinal-type rather than in diffuse/mixed-type tumors (13.9% vs. 10%); however, none were statistically significant. Median survival was 5 months in HER2-positive patients and 4 months in HER2-negative patients. HER2 was not significantly associated with two-year survival (HR [95% CI] = 1.12 [0.61, 2.06]). Mortality in patients with palliative therapy was higher than that of those with definitive/therapeutic therapy (76.8% vs 75.8%; HR = 1.547 [1.022, 2.343]). The combination of resection and chemotherapy intervention provided a protective effect on mortality with HR = 0.456 [0.219, 0.95]. There was a significant association between resection-chemotherapy combination therapy and survival in subjects with negative HER2 expression (HR = 0.409 [0.176, 0.947].
Conclusion: In this study, HER2 expression in gastric adenocarcinoma was 12.3%. HER2 expression tended to be higher in liver metastases, Borrmann type I/II, moderate differentiation, and intestinal type histopathology results. Combination therapy with resection and chemotherapy had a protective effect on mortality in this study. Median survival in HER2-positive patients was higher than in HER2-negative patients, but HER2 expression status was not a prognostic factor for two-year survival in gastric adenocarcinoma
Keywords
References
Ang TL, Fock KM. Clinical epidemiology of gastric cancer. Singapore Med J. 2014;55(12):621.
Ferlay J, Shin H, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917.
Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893–907.
Matsuda T, Saika K. The 5-year relative survival rate of stomach cancer in the USA, Europe and Japan. Jpn J Clin Oncol. 2013;43(11):1157–8.
Dicken BJ, Bigam DL, Cass C, Mackey JR, Joy AA, Hamilton SM. Gastric adenocarcinoma: review and considerations for future directions. Ann Surg. 2005;241(1):27–39.
Siregar GA. Early gastric cancer. Indones J Gastroenterol Hepatol Dig Endosc. 2002;3(3):91–6.
Machlowska J, Baj J, Sitarz M, Maciejewski R, Sitarz R. Gastric cancer: epidemiology, risk factors, classification, genomic characteristics and treatment strategies. Int J Mol Sci. 2020;21(11):4012.
Wang HB, Liao XF, Zhang J. Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis. Medicine (Baltimore). 2017;96(44):e8437.
Janjigian YY, Werner D, Pauligk C, Steinmetz K, Kelsen DP, Jäger E, et al. Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis. Ann Oncol. 2012;23(10):2656–62.
Smolińska M, Grzanka D, Antosik P, Kasperska A, Neska-Długosz I, Jóźwicki J, et al. HER2, NF-κB, and SATB1 Expression Patterns in Gastric Cancer and Their Correlation with Clinical and Pathological Parameters. Dis Markers. 2019;2019(1):6315936.
Yonemura Y, Ninomiya I, Yamaguchi A, Fushida S, Kimura H, Ohoyama S, et al. Evaluation of immunoreactivity for erbB-2 protein as a marker of poor short term prognosis in gastric cancer. Cancer Res. 1991;51(3):1034–8.
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376(9742):687–97.
Chua TC, Merrett ND. Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes—A systematic review. Int J Cancer. 2012;130(12):2845–56.
Roy PS, Nyodu T, Hazarika M, Saikia BJ, Bhuyan C, Inamdar A, et al. Prevalence of HER2 expression and its correlation with clinicopathological parameters in gastric or gastroesophageal junction adenocarcinoma in NorthEast Indian population. Asian Pac J Cancer Prev. 2019;20(4):1139.
Pathmanathan N, Geng J, Li W, Nie X, Veloso J, Wang J, et al. Human epidermal growth factor receptor 2 status of gastric cancer patients in Asia: results from a large, multicountry study. Asia Pac J Clin Oncol. 2017;13(3):249–60.
Setiawati D, Handjari DR, Rustamadji P. Ekspresi HER2 pada Adenokarsinoma Gaster dan Hubungannya dengan Tipe Histopatologik dan Derajat Diferensiasi. Maj Patol Indones. 2014;23(1).
Pinto-de-Sousa J, David L, Almeida R, Leitao D, Preto JR, Seixas M, et al. c-erb B-2 expression is associated with tumor location and venous invasion and influences survival of patients with gastric carcinoma. Int J Surg Pathol. 2002;10(4):247–56.
Park DI, Yun JW, Park JH, Oh SJ, Kim HJ, Cho YK, et al. HER2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51(8):1371–9.
Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Benson AB III, et al. HER2 testing and clinical decision making in gastroesophageal adenocarcinoma: guideline from the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology. Am J Clin Pathol. 2016;146(6):647–69.
Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014;17(1):1–12.
Junior PNA, Neto RA, Forones NM. HER2 expression as a prognostic factor in metastatic gastric cancer. Arq Gastroenterol. 2016;53:62–7.
Shitara K, Yatabe Y, Matsuo K, Sugano M, Kondo C, Takahari D, et al. Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer. 2013;16(2):261–7.
Dai X, Zhang X, Yu J. Clinicopathological features and Borrmann classification associated with HER2-positive in primary gastric cancer. Clin Exp Gastroenterol. 2019;287–94.
Kurokawa Y, Matsuura N, Kimura Y, Adachi S, Fujita J, Imamura H, et al. Multicenter large-scale study of prognostic impact of HER2 expression in patients with resectable gastric cancer. Gastric Cancer. 2015;18(4):691–7.
Yıldız Y, Sokmensuer C, Yalcin S. Evaluation of c-Met, HGF, and HER2 expressions in gastric carcinoma and their association with other clinicopathological factors. Onco Targets Ther. 2016;5809–17.
Rüschoff J, Hanna W, Bilous M, Hofmann M, Osamura RY, Penault-Llorca F, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637–50.
Cho J, Jeong J, Sung J, Sung CO, Kim KM, Park CK, et al. A large cohort of consecutive patients confirmed frequent HER2 positivity in gastric carcinomas with advanced stages. Ann Surg Oncol. 2013;20(Suppl 3):477–84.
Tanner M, Gancberg D, Di Leo A, Larsimont D, Rouas G, Piccart MJ, et al. Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER2/neu oncogene amplification in archival breast cancer samples. Am J Pathol. 2000;157(5):1467–72.
Dahlan M. Analisis Multivariat Regresi Logistik. Jakarta: PT Epidemiologi Indonesia (Pstat-Consulting); 2012.
Dahlan M. Analisis Survival. 2nd ed. Jakarta: Sagung Seto; 2014.
De Carli DM, Rocha MP da, Antunes LCM, Fagundes RB. Expressão imunoistoquímica do HER2 no adenocarcinoma de estômago. Arq Gastroenterol. 2015;52:152–5.
Rajadurai P, Fatt HK, Ching FY. Prevalence of HER2 positivity and its clinicopathological correlation in locally advanced/metastatic gastric cancer patients in Malaysia. J Gastrointest Cancer. 2018;49(2):150–7.
Ougolkov A, Yamashita K, Bilim V, Takahashi Y, Mai M, Minamoto T. Abnormal expression of E-cadherin, β-catenin, and c-erbB-2 in advanced gastric cancer: its association with liver metastasis. Int J Colorectal Dis. 2003;18(2):160–6.
Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: from benchside to practice. World J Gastroenterol. 2016;22(26):5879.
Gullo I, Carneiro F, Oliveira C, Almeida GM. Heterogeneity in gastric cancer: from pure morphology to molecular classifications. Pathobiology. 2018;85(1–2):50–63.
Uprak TK, Attaallah W, Çelikel ÇA, Ayrancı G, Yeğen C. HER2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. Turkish J Surg. 2015;31(4):207.
Lee JS, Kim SH, Im SA, Kim MA, Han JK. Human epidermal growth factor receptor 2 expression in unresectable gastric cancers: relationship with CT characteristics. Korean J Radiol. 2017;18(5):809–20.
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DOI: 10.24871/2722026119-126
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