EVALUATION OF HER2/NEU STATUS IN GASTRIC CARCINOMA USING IMMUNOHISTOCHEMISTRY AND FISH TECHNIQUES
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Keywords
Gastric carcinoma, HER2/neu, Immunohistochemistry, Fluorescence In Situ Hybridization, Targeted therapy, Gene amplification
Abstract
Background:
Gastric carcinoma remains a major global health concern, with a high mortality rate due to late diagnosis and limited targeted therapies. Overexpression or amplification of the HER2/neu (Human Epidermal Growth Factor Receptor 2) gene has been identified in a subset of gastric cancers and is associated with aggressive tumor behavior and poor prognosis. Accurate determination of HER2 status is essential for selecting patients eligible for HER2-targeted therapy. This study aims to evaluate HER2/neu expression in gastric carcinoma using Immunohistochemistry (IHC) and confirmatory Fluorescence In Situ Hybridization (FISH) techniques.
Materials and Methods:
A total of 60 histologically confirmed gastric carcinoma cases were retrospectively analyzed. Formalin-fixed paraffin-embedded (FFPE) tissue sections were subjected to HER2/neu IHC staining. Scoring was done according to the modified Hofmann criteria for gastric cancer. Cases showing IHC scores of 2+ (equivocal) or 3+ (positive) were further evaluated using FISH to assess HER2 gene amplification.
Results:
Out of 60 cases, HER2/neu overexpression (IHC 3+) was observed in 12 cases (20%), while 18 cases (30%) showed equivocal staining (2+). Negative expression (0 and 1+) was seen in 30 cases (50%). Among the 18 equivocal cases, FISH detected HER2 gene amplification in 10 cases (55.6%). Overall, HER2 positivity confirmed by either IHC 3+ or FISH amplification was noted in 22 cases (36.7%). HER2 positivity was more frequent in intestinal-type gastric carcinoma and tumors located at the gastroesophageal junction.
Conclusion:
HER2/neu expression is present in a significant proportion of gastric carcinoma cases, highlighting its potential as a therapeutic target. Combining IHC with FISH provides a more reliable assessment of HER2 status, especially in equivocal cases. Routine evaluation of HER2 is recommended in gastric cancer for better prognostication and treatment planning.
References
2. Fassan M, Ludwig K, Pizzi M, Castoro C, Guzzardo V, Balistreri M, et al. Human epithelial growth factor receptor 2 (HER2) status in primary and metastatic esophagogastric junction adenocarcinomas. Hum Pathol. 2012;43(8):1206–12. doi:10.1016/j.humpath.2011.09.004. PMID: 22217477.
3. Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol. 2011;18(1):53–9. doi:10.1097/PAP.0b013e3182026d72. PMID: 21169738.
4. Fox SB, Kumarasinghe MP, Armes JE, Bilous M, Cummings MC, Farshid G, et al. Gastric HER2 Testing Study (GaTHER): an evaluation of gastric/gastroesophageal junction cancer testing accuracy in Australia. Am J Surg Pathol. 2012;36(4):577–82. doi:10.1097/PAS.0b013e318244adbb. PMID: 22314190.
5. Tafe LJ, Janjigian YY, Zaidinski M, Hedvat CV, Hameed MR, Tang LH, et al. Human epidermal growth factor receptor 2 testing in gastroesophageal cancer: correlation between immunohistochemistry and fluorescence in situ hybridization. Arch Pathol Lab Med. 2011;135(11):1460–5. doi:10.5858/arpa.2010-0541-OA. PMID: 22032573.
6. Park YS, Hwang HS, Park HJ, Ryu MH, Chang HM, Yook JH, et al. Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use? Hum Pathol. 2012;43(3):413–22. doi:10.1016/j.humpath.2011.05.019. PMID: 21855114.
7. Kanta SY, Yamane T, Dobashi Y, Mitsui F, Kono K, Ooi A. Topoisomerase IIalpha gene amplification in gastric carcinomas: correlation with the HER2 gene. An immunohistochemical, immunoblotting, and multicolor fluorescence in situ hybridization study. Hum Pathol. 2006;37(10):1333–43. doi:10.1016/j.humpath.2006.05.008. PMID: 16949920.
8. Subasinghe D, Acott N, Kumarasinghe MP. A survival guide to HER2 testing in gastric/gastroesophageal junction carcinoma. Gastrointest Endosc. 2019;90(1):44–54. doi:10.1016/j.gie.2019.03.022. PMID: 30928424.
9. Bang YJ. Advances in the management of HER2-positive advanced gastric and gastroesophageal junction cancer. J Clin Gastroenterol. 2012;46(8):637–48. doi:10.1097/MCG.0b013e3182557307. PMID: 22751336.
10. Fassan M, Mastracci L, Grillo F, Zagonel V, Bruno S, Battaglia G, et al. Early HER2 dysregulation in gastric and oesophageal carcinogenesis. Histopathology. 2012;61(5):769–76. doi:10.1111/j.1365-2559.2012.04272.x. PMID: 22882541.
11. Shan 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. doi:10.1186/1746-1596-8-76. PMID: 23656792.
12. Lorenzen S, Lordick F. How will human epidermal growth factor receptor 2-neu data impact clinical management of gastric cancer? Curr Opin Oncol. 2011;23(4):396–402. doi:10.1097/CCO.0b013e3283469567. PMID: 21505336.
13. Jeung J, Patel R, Vila L, Wakefield D, Liu C. Quantitation of HER2/neu expression in primary gastroesophageal adenocarcinomas using conventional light microscopy and quantitative image analysis. Arch Pathol Lab Med. 2012;136(6):610–7. doi:10.5858/arpa.2011-0371-OA. PMID: 22646266.
14. Abrahao-Machado LF, Scapulatempo-Neto C. HER2 testing in gastric cancer: An update. World J Gastroenterol. 2016;22(19):4619–25. doi:10.3748/wjg.v22.i19.4619. PMID: 27217694.
15. Perrone G, Amato M, Callea M, Rabitti C, Righi D, Crucitti P, et al. HER2 amplification status in gastric and gastro-oesophageal junction cancer in routine clinical practice: which sample should be used? Histopathology. 2012;61(1):134–5. doi:10.1111/j.1365-2559.2012.04251.x. PMID: 22551459.
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Dr Jaymin Bhatt
Professor & Head, Department of Pathology, Nootan Medical College and Research Center, Visnagar, Gujarat, India
Dr Divyesh Goswami
Associate Professor, Department of Pathology, Nootan Medical College and Research Center, Visnagar, Gujarat, India
Dr Yash Modh
Assistant Professor, Department of Pathology, Nootan Medical College and Research Center, Visnagar, Gujarat, India