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HER2 Status in Gastric and Gastroesophageal Carcinomas: Evaluation of Histopathological Fingings, Paired ResectionBiopsy Specimens, and the Effect of Neoadjuvant Therapy: A Single Center Study
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Abstract
Background/Aims: Accurately determining the human epidermal growth factor receptor 2 (HER2) status is crucial in identifying suitable candidates for targeted therapy in gastric cancer, considering the cost and potential side effects of anti-HER2 treatments. This study aimed to assess HER2 overexpression/amplification prevalence in gastric and gastroesophageal cancer patients, its correlation with clinicopathological characteristics, and the consistency of HER2 status between biopsy and radical specimens.
Materials and Methods: We analyzed data from 667 specimens of 600 gastric/gastroesophageal cancer patients at Dokuz Eylül University Faculty of Medicine from 2012 to 2021. The correlation of HER2 expression and amplification status and clinicopathological parameters were assessed. Furthermore, we compared HER2 status concordance between paired biopsy-radical specimens when both endoscopic and radical materials were present. Additionally, we compared HER2 status before and after treatment in patients receiving neoadjuvant chemotherapy.
Results: In our study, +3 HER2 immunohistochemistry results were more common in gastroesophageal junction tumors (23%). Human epidermal growth factor receptor 2 immunohistochemistry positivity and HER2 gene amplification were found to be significantly more common in males, people over 65 years of age, and intestinal morphology. Overall concordance of HER2 status between radical and biopsy materials was 95.5%.
Conclusion: The high HER2 concordance between the paired biopsy and radical samples holds significant importance in clinical management. This finding is particularly noteworthy since the HER2 assessment can generally be conducted on small/limited biopsy materials in routine practice. Our study is the most extensive series from Türkiye and the Balkans, which will shed light on our country’s data by investigating the relationship of HER2 with clinicopathological parameters in gastric/gastroesophageal carcinomas.
Cite this article as:Yuzuguldu RI, Sagol O, Unlu M, et al. HER2 status in gastric and gastroesophageal carcinomas: evaluation of histopathological findings, paired resection-biopsy specimens, and the effect of neoadjuvant therapy: A single center study. Turk J
Gastroenterol. 2025;36(6):357-370.
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References
1. Ilic M, Ilic I. Epidemiology of stomach cancer. World J Gastroenterol. 2022;28(12):1187-1203. [CrossRef]
2. Laurén P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. Acta Pathol Microbiol Scand. 1965;64:31-49. [CrossRef]
3. World Health Organization. International Agency for Research on Cancer. WHO Classification of Tumours: Digestive System Tumours. 5th ed. 2019.
4. Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T. The product of the human cerbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science. 1986;232(4758):1644-1646. [CrossRef]
5. Van 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. [CrossRef]
6. TCGA. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014;513(7517):202-209. [CrossRef]
7. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52(7):797-805. [CrossRef]
8. Lee S, de Boer WB, Fermoyle S, Platten M, Kumarasinghe MP. Human epidermal growth factor receptor 2 testing in gastric carcinoma: issues related to heterogeneity in biopsies and resections. Histopathology. 2011;59(5):832-840. [CrossRef]
9. Seo S, Ryu MH, Park YS, et al. Loss of HER2 positivity after anti-HER2 chemotherapy in HER2-positive gastric cancer patients: results of the GASTric cancer HER2 reassessment study 3 (GASTHER3). Gastric Cancer. 2019;22(3):527-535. [CrossRef]
10. Makiyama A, Sukawa Y, Kashiwada T, et al. Randomized, Phase II study of trastuzumab beyond progression in patients with HER2-positive advanced gastric or gastroesophageal junction cancer: WJOG7112G (T-ACT Study). J Clin Oncol. 2020;38(17):1919-1927. [CrossRef]
11. Bray 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. [CrossRef]
12. Wang HB, Liao X-F, Zhang J. Clinicopathological factors associated with HER2-positive gastric cancer: a meta-analysis. Med (Baltim). 2017;96(44):e8437. [CrossRef]
13. Janjigian YY, Werner D, Pauligk C, 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):2656-2662. [CrossRef]
14. Rüschoff J. Adenocarcinoma of the GEJ: gastric or oesophageal cancer?. Recent Results Cancer Res. 2012;196:107-113. [CrossRef]
15. Wu AH, Tseng CC, Bernstein L. Hiatal hernia, reflux symptoms, body size, and risk of esophageal and gastric adenocarcinoma. Cancer. 2003;98(5):940-948. [CrossRef]
16. Kataoka Y, Okabe H, Yoshizawa A, et al. HER2 expression and its clinicopathological features in resectable gastric cancer. Gastric Cancer. 2013;16(1):84-93. [CrossRef]
17. Hui LI, Rongwei JI. Analysis of perineural invasion with HER-2 expression and its correlation in patients with advanced gastric cancer. Chin J Clin Exp Pathol. 2017;12:178-182.
18. Mei Y, Wang S, Feng T, et al. Nomograms involving HER2 for predicting lymph node metastasis in early gastric cancer. Front Cell Dev Biol. 2021;9:781824. [CrossRef]
19. Gürbüz M, Doğan İ, Akkuş E, et al. Clinicopathological factors in relation to HER2 status in metastatic gastric cancer: a retrospective observational study. J Oncol Sci. 2022;8(1):14-19. [CrossRef]
20. Abali H, Yalcin S, Onal HC, et al. A Phase II study of the combination of oxaliplatin, capecitabine, and trastuzumab and chemoradiotherapy in the adjuvant setting in operated patients with HER2-positive gastric or gastroesophageal junction cancer (TOXAG study): a Turkish oncology group study. Am J Clin Oncol. 2021;44(7):301-307. [CrossRef]
21. Uprak TK, Attaallah W, Çelikel ÇA, Ayranci G, Yeʇen C. HER-2 incidence in gastric cancer, its association with prognosis and clinicopathological parameters. Turk J Surg. 2015;31(4):207-213. [CrossRef]
22. Takehana T, Kunitomo K, Kono K, et al. Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay. Int J Cancer. 2002;98(6):833-837. [CrossRef]
23. Tanner M, Hollmén M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with topoisomerase II alpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16(2):273-278. [CrossRef]
24. Gomez-Martin C, Plaza JC, Pazo-Cid R, et al. Level of HER2 gene amplification predicts response and overall survival in HER2-positive advanced gastric cancer treated with trastuzumab. J Clin Oncol. 2013;31(35):4445-4452. [CrossRef]
25. Rüschoff J, Hanna W, Bilous M, et al. HER2 testing in gastric cancer: a practical approach. Mod Pathol. 2012;25(5):637-650. [CrossRef]
26. Wang T, Amemiya Y, Henry P, Seth A, Hanna W, Hsieh ET. Multiplex ligation-dependent probe amplification can clarify HER2 status in gastric cancers with “polysomy 17”. J Cancer. 2015;6(5):403-408. [CrossRef]
27. Yoshida H, Yamamoto N, Taniguchi H, et al. Comparison of HER2 status between surgically resected specimens and matched biopsy specimens of gastric intestinal-type adenocarcinoma. Virchows Arch. 2014;465(2):145-154. [CrossRef]
28. Huber AR, Buscaglia B, Koltz BR, et al. Impact of specimen type and specimen number on HER2 status in gastroesophageal junction and gastric adenocarcinoma. Am J Clin Pathol. 2019;151(5):461-468. [CrossRef]
29. Pirrelli M, Caruso ML, Di Maggio M, Armentano R, Valentini AM. Are biopsy specimens predictive of HER2 status in gastric cancer patients?. Dig Dis Sci. 2013;58(2):397-404. [CrossRef]
30. Wang T, Hsieh ET, Henry P, Hanna W, Streutker CJ, Grin A. Matched biopsy and resection specimens of gastric and gastroesophageal adenocarcinoma show high concordance in HER2 status. Hum Pathol. 2014;45(5):970-975. [CrossRef]
31. Kanayama K, Imai H, Yoneda M, Hirokawa YS, Shiraishi T. Significant intratumoral heterogeneity of human epidermal growth factor receptor 2 status in gastric cancer: a comparative study of immunohistochemistry, FISH, and dual-color in situ hybridization. Cancer Sci. 2016;107(4):536-542. [CrossRef]
32. Satala CB, Jung I, Stefan-van Staden RI, et al. HER2 heterogeneity in gastric cancer: a comparative study, using two commercial antibodies. J Oncol. 2020;2020:8860174. [CrossRef]
33. Lim B, Kim JH, Kim M, Kim SY. Genomic and epigenomic heterogeneity in molecular subtypes of gastric cancer. World J Gastroenterol. 2016;22(3):1190-1201. [CrossRef]
34. Yamaguchi K, Bang YJ, Iwasa S, et al. Trastuzumab deruxtecan in anti-human epidermal growth factor receptor 2 treatment-naive patients with human epidermal growth factor receptor 2-low gastric or gastroesophageal junction adenocarcinoma: exploratory cohort results in a Phase II trial. J Clin Oncol. 2022;41:816-825. [CrossRef]
35. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet. 2020;396(10251):635-648. [CrossRef]
36. Bang Y-J, Van Cutsem E, Feyereislova 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(9749):687-697. [CrossRef]
37. Wagner AD, Grabsch HI, Mauer M, et al. EORTC-1203-GITCG – the “INNOVATION”-trial: effect of chemotherapy alone versus chemotherapy plus trastuzumab, versus chemotherapy plus trastuzumab plus pertuzumab, in the perioperative treatment of HER2 positive, gastric and gastroesophageal junction adenocarcinoma on pathologic response rate: a randomized phase II-intergroup trial of the EORTC-Gastrointestinal Tract Cancer Group, Korean Cancer Study Group and Dutch Upper GI-Cancer group. BMC Cancer. 2019;19(1):494. [CrossRef]
38. Hofheinz RD, Merx K, Haag GM, et al. FLOT versus FLOT/Trastuzumab/Pertuzumab perioperative therapy of human epidermal growth factor receptor 2-positive resectable esophagogastric adenocarcinoma: a randomized Phase II trial of the AIO EGA study group. J Clin Oncol. 2022;40(32):3750-3761. [CrossRef]
39. Janjigian YY, Sanchez-Vega F, Jonsson P, et al. Genetic predictors of response to systemic therapy in esophagogastric cancer. Cancer Discov. 2018;8(1):49-58. [CrossRef]
40. Shu S, Iimori M, Nakanishi R, et al. Changes in HER2 expression and amplification status following preoperative chemotherapy for gastric cancer. In Vivo. 2018;32(6):1491-1498. [CrossRef]