Abstract
Objective: Data available on the rate of human epidermal growth factor receptor 2 (HER2) positivity and clinicopathological
parameters related to it are heterogeneous. Hence, it is pertinent to investigate these parameters in different populations. This study aims to
determine the frequency of HER2 positivity and clinicopathological factors associated with it in metastatic gastric cancer patients in a Turkish
population. Material and Methods: This study included 552 patients with metastatic gastric cancer from 5 oncology centers. HER2 status,
age, gender, smoking and alcohol history, body mass index, basal carcino embryonic antigen (CEA) level, basal cancer antigen 19-9 (CA
19-9) level, tumor localization, de-novo metastatic cancer, Lauren classification, signet-ring cell component, venous and neural invasion, and
histological grade data were collected retrospectively. HER2 positivity was defined as an immunohistochemistry (IHC) score of 3+ or an IHC
score of 2+ and in situ hybridization positive. Univariable and multivariable logistic regression analyses were used to detect clinicopathological
factors associated with HER2 status. Results: A total of 100 patients (18.1%) were HER2-positive. Alcohol consumption, basal CEA level,
basal CA 19-9 level, and signet-ring cell component were found to be statistically significant in univariable analysis. Alcohol use, basal CEA
level, and having signet-ring cell component were statistically significant in the multivariable analysis. Odds ratios of alcohol use, high basal
CEA and having signet-ring component were 2.35 (95% confidence interval (CI): 1.27-4.36, p=0.006), 1.99 (95% CI: 1.19-3.36, p=0.009),
and 0.39 (95% CI: 0.22-0.71, p=0.002) respectively. Conclusion: HER2 positivity was detected in 18.1% of metastatic gastric cancer patients
in the Turkish population. Alcohol use and basal CEA level were positively, and the signet-ring cell component was negatively correlated with
HER2 positivity.
Keywords:
Gastric cancer, HER2, clinicopathological factors, ISH
References
1Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424. Erratum in: CA Cancer J Clin. 2020; 70(4):313.
2Smyth EC, Verheij M, Allum W, Cunningham D, Cervantes A, Arnold D; ESMO Guidelines Committee. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2016;27(suppl 5):v38-v49.
3Casalini P, Iorio MV, Galmozzi E, Ménard S. Role of HER receptors family in development and differentiation. J Cell Physiol. 2004; 200(3):343-350.
4Bang YJ, Van Cutsem E, Feyereislova A, et al; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemo therapy 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):687-697. Erratum in: Lancet. 2010; 376(9749):1302.
5Koopman T, Smits MM, Louwen M, Hage M, Boot H, Imholz AL. HER2 positivity in gastric and esophageal adenocarcinoma: clinicopathological analysis and comparison. J Cancer Res Clin Oncol. 2015;141(8):1343-1351.
6Fornaro L, Vivaldi C, Parnofiello A, et al. Validated clinico-pathologic nomogram in the prediction of HER2 status in gastro-oesophageal cancer. Br J Cancer. 2019;120(5):522-526.
7Van Cutsem E, Bang YJ, Feng-Yi F, et al. HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer. Gastric Cancer. 2015;18(3):476-484.
8Wang HB, Liao XF, Zhang J. Clinicopathological factors associated with HER2-positive gastric cancer: A meta-analysis. Medicine (Baltimore). 2017;96(44):e8437. Erratum in: Medicine (Baltimore). 2017;96(52):e9530.
9Park JS, Rha SY, Chung HC, et al. Clinicopathological features and prognostic significance of HER2 expression in gastric cancer. Oncology. 2015;88(3):147-156.
10Rajadurai 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):150-157.
11Matsusaka S, Nashimoto A, Nishikawa K, et al. Clinicopathological factors associated with HER2 status in gastric cancer: results from a prospective multicenter observational cohort study in a Japanese population (JFMC44-1101). Gastric Cancer. 2016;19(3):839-851. Erratum in: Gastric Cancer. 2016;19(3): 1026.
12Shan L, Ying J, Lu N. HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagn Pathol. 2013;8:76.
13He C, Bian XY, Ni XZ, et al. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer. World J Gastroenterol. 2013;19(14):2171-2178.
14Lei YY, Huang JY, Zhao QR, et al. The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature. World J Surg Oncol. 2017;15(1):68.
15Lindblad M, Rodríguez LA, Lagergren J. Body mass, tobacco and alcohol and risk of esophageal, gastric cardia, and gastric non-cardia adenocarcinoma among men and women in a nested case-control study. Cancer Causes Control. 2005;16(3):285-294.
