Relationship between HER2 and clinicopathological data in gastric adenocarcinomas

HER2 status in gastric adenocarcinomas

Authors

Keywords:

Clinicopathological features, Gastric cancer, HER2, Immunohistochemistry, Prognostic factor

Abstract

Background/Aim: The impact of human epidermal growth factor receptor 2 (HER2) overexpression on the surveillance of gastric cancer remains uncertain. Typically, HER2 status is assessed in both locally advanced and metastatic diseases, and targeted therapies are applied to cases with HER2-positive status. Our objective was to investigate the correlation between HER2 receptor status, clinicopathological characteristics, and prognosis in gastric cancers across all stages. Based on the results from this investigation, we aim to provide clinicians with insights into the clinicopathological conditions that warrant HER2 investigation.

Methods: In this retrospective study, we conducted a comprehensive analysis of clinicopathological data from a cohort of 169 patients who underwent surgical treatment for gastric cancer between 2014 and 2022. The HER2 status was determined based on results from immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) techniques applied to gastric cancer pathology samples. Based on the HER2 positivity, the patients were classified into two distinct groups: (1) HER2-positive and (2) HER2-negative. The relationship between the clinicopathological variables, HER2 status, and overall survival (OS) was evaluated using chi-squared and Kaplan–Meier analyses. A statistical significance level of P <0.05 was applied to determine significant associations.

Results: According to the IHC analyses performed in our study population, 33 among 169 patients were HER2-positive (19.53%). Statistically significant factors related to HER2 positivity, such as male gender (P=0.009), pathological stage, N category, lymphovascular invasion status ([LVI] P=0.046), and proximal tumor location (P=0.015) were observed. In addition, OS was 40.49 (6.21) months in HER2-positive gastric cancer patients and 57.43 (3.48) months in HER2-negative gastric cancers (P=0.045).

Conclusion: Irrespective of the pathological stage, gastric cancer exhibited HER2 positivity at a ratio of 5:1. Among the clinicopathological findings, a significant correlation was observed between HER2 expression and gastric cancers characterized by aggressive features. Moreover, HER2 positivity was associated with an unfavorable prognosis in gastric cancer patients.

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References

Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016 Nov 26;388(10060):2654-64. doi: 10.1016/S0140-6736(16)30354-3. Epub 2016 May 5. PMID: 27156933. DOI: https://doi.org/10.1016/S0140-6736(16)30354-3

Meric-Bernstam F, Johnson AM, Dumbrava EEI, Raghav K, Balaji K, Bhatt M, et al. Advances in HER2-Targeted Therapy: Novel Agents and Opportunities Beyond Breast and Gastric Cancer. Clin Cancer Res. 2019 Apr 1;25(7):2033-41. doi: 10.1158/1078-0432.CCR-18-2275. Epub 2018 Nov 15. PMID: 30442682; PMCID: PMC6445731. DOI: https://doi.org/10.1158/1078-0432.CCR-18-2275

Tebbutt N, Pedersen MW, Johns TG. Targeting the ERBB family in cancer: couples therapy. Nat Rev Cancer. 2013 Sep;13(9):663-73. doi: 10.1038/nrc3559. Epub 2013 Aug 16. PMID: 23949426. DOI: https://doi.org/10.1038/nrc3559

Choi B, Cha M, Eun GS, Lee DH, Lee S, Ehsan M, et al. Single-molecule functional anatomy of endogenous HER2-HER3 heterodimers. Elife. 2020 Apr 8;9:e53934. doi: 10.7554/eLife.53934. PMID: 32267234; PMCID: PMC7176432. DOI: https://doi.org/10.7554/eLife.53934

Vranić S, Bešlija S, Gatalica Z. Targeting HER2 expression in cancer: New drugs and new indications. Bosn J Basic Med Sci. 2021 Feb 1;21(1):1-4. doi: 10.17305/bjbms.2020.4908. PMID: 32530388; PMCID: PMC7861626. DOI: https://doi.org/10.17305/bjbms.2020.4908

Sakai K, Mori S, Kawamoto T, Taniguchi S, Kobori O, Morioka Y, et al. Expression of epidermal growth factor receptors on normal human gastric epithelia and gastric carcinomas. J Natl Cancer Inst. 1986 Nov;77(5):1047-52. PMID: 3464796.

Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol. 2008 Sep;19(9):1523-9. doi: 10.1093/annonc/mdn169. Epub 2008 Apr 25. PMID: 18441328. DOI: https://doi.org/10.1093/annonc/mdn169

Hofmann M, Stoss O, Shi D, Büttner R, van de Vijver M, Kim W, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008 Jun;52(7):797-805. doi: 10.1111/j.1365-2559.2008.03028.x. Epub 2008 Apr 18. PMID: 18422971. DOI: https://doi.org/10.1111/j.1365-2559.2008.03028.x

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 Oct;18(4):691-7. doi: 10.1007/s10120-014-0430-7. Epub 2014 Sep 16. PMID: 25224659. DOI: https://doi.org/10.1007/s10120-014-0430-7

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. ToGA Trial Investigators. 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 Aug 28;376(9742):687-97. doi: 10.1016/S0140-6736(10)61121-X. Epub 2010 Aug 19. Erratum in: Lancet. 2010 Oct 16;376(9749):1302. PMID: 20728210. DOI: https://doi.org/10.1016/S0140-6736(10)61121-X

Brierley JD, Gospodarowicz MK, Wittekind C. The TNM classification of malignant tumours. 8. Oxford: Wiley Blackwell; 2017. DOI: https://doi.org/10.1002/9780471420194.tnmc26.pub3

Matsusaka S, Nashimoto A, Nishikawa K, Miki A, Miwa H, Yamaguchi 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 Jul;19(3):839-51. doi: 10.1007/s10120-015-0518-8. Epub 2015 Aug 12. Erratum in: Gastric Cancer. 2016 Jul;19(3):1026. PMID: 26265390; PMCID: PMC4906061. DOI: https://doi.org/10.1007/s10120-015-0518-8

Tang D, Liu CY, Shen D, Fan S, Su X, Ye P, et al. Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas. Onco Targets Ther. 2014 Dec 16;8:7-14. doi: 10.2147/OTT.S70922. PMID: 25565860; PMCID: PMC4274138. DOI: https://doi.org/10.2147/OTT.S70922

Liang JW, Zhang JJ, Zhang T, Zheng ZC. Clinicopathological and prognostic significance of HER2 overexpression in gastric cancer: a meta-analysis of the literature. Tumour Biol. 2014;35(5):4849–58. DOI: https://doi.org/10.1007/s13277-014-1636-3

Grabsch H, Sivakumar S, Gray S, Gabbert HE, Müller W. HER2 expression in gastric cancer: Rare, heterogeneous and of no prognostic value - conclusions from 924 cases of two independent series. Cell Oncol. 2010;32(1-2):57-65. doi: 10.3233/CLO-2009-0497. PMID: 20208134; PMCID: PMC4619246. DOI: https://doi.org/10.1155/2010/519498

Li H, Li L, Zhang N, Wang Z, Xu N, Linghu E, et al. Relationship between HER2 overexpression and long-term outcomes of early gastric cancer: a prospective observational study with a 6-year follow-up. BMC Gastroenterol. 2022 May 13;22(1):238. doi: 10.1186/s12876-022-02309-7. PMID: 35562663; PMCID: PMC9102633. DOI: https://doi.org/10.1186/s12876-022-02309-7

Fisher SB, Fisher KE, Squires MH 3rd, Patel SH, Kooby DA, El-Rayes BF, et al. HER2 in resected gastric cancer: Is there prognostic value? J Surg Oncol. 2014 Feb;109(2):61-6. doi: 10.1002/jso.23456. Epub 2013 Oct 10. PMID: 24122802. DOI: https://doi.org/10.1002/jso.23456

Wang H, Xing XM, Ma LN, Liu L, Hao J, Feng LX, et al. Metastatic lymph node ratio and Lauren classification are independent prognostic markers for survival rates of patients with gastric cancer. Oncol Lett. 2018 Jun;15(6):8853-62. doi: 10.3892/ol.2018.8497. Epub 2018 Apr 13. PMID: 29844813; PMCID: PMC5958805.

Liu X, Xu P, Qiu H, Liu J, Chen S, Xu D, et al. Clinical utility of HER2 assessed by immunohistochemistry in patients undergoing curative resection for gastric cancer. Onco Targets Ther. 2016 Feb 26;9:949-58. doi: 10.2147/OTT.S100979. PMID: 27013889; PMCID: PMC4777257. DOI: https://doi.org/10.2147/OTT.S100979

Ngaiza A, Vuhahula E, Yahaya J, Ndayisaba MC, Kawishe GJ, Grenert JP, et al. Evaluation of Human Epidermal Growth Factor Receptor 2 Expression in Gastric and Gastroesophageal Cancers in Tanzania. Arch Pathol Lab Med. 2022 Dec 1;146(12):1523-9. doi: 10.5858/arpa.2021-0394-OA. PMID: 35344993; PMCID: PMC9515243. DOI: https://doi.org/10.5858/arpa.2021-0394-OA

Choi S, Song JH, Lee S, Cho M, Kim YM, Kim HI, et al. Lymphovascular Invasion: Traditional but Vital and Sensible Prognostic Factor in Early Gastric Cancer. Ann Surg Oncol. 2021 Dec;28(13):8928-35. doi: 10.1245/s10434-021-10224-6. Epub 2021 Jun 1. PMID: 34075484. DOI: https://doi.org/10.1245/s10434-021-10224-6

Fujikawa H, Koumori K, Watanabe H, Kano K, Shimoda Y, Aoyama T, et al. The Clinical Significance of Lymphovascular Invasion in Gastric Cancer. In Vivo. 2020 May-Jun;34(3):1533-9. doi: 10.21873/invivo.11942. PMID: 32354959; PMCID: PMC7279808. DOI: https://doi.org/10.21873/invivo.11942

Laboissiere RS, Buzelin MA, Balabram D, De Brot M, Nunes CB, Rocha RM, et al. Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections. BMC Gastroenterol. 2015 Nov 4;15:157. doi: 10.1186/s12876-015-0384-1. PMID: 26530403; PMCID: PMC4632681. DOI: https://doi.org/10.1186/s12876-015-0384-1

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Published

2023-01-11

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Research Article

How to Cite

1.
Ceylan C, Angin YS, Baran NT, Kocaaslan H, Cengiz E, Güngörür O, Güzel M, Saglam K, Aydin C. Relationship between HER2 and clinicopathological data in gastric adenocarcinomas: HER2 status in gastric adenocarcinomas. J Surg Med [Internet]. 2023 Jan. 11 [cited 2024 Jun. 13];8(1):7-11. Available from: https://jsurgmed.com/article/view/7588