HER2/neu Expression in Gastrointestinal Carcinoma Among South Indians
Keywords:
HER2, Gastric carcinoma, Colorectal cancers, Small intestinal carcinoma
Abstract
Background: HER2/neu oncogene overexpression and amplification in breast cancer is well known. Studies have proved its role in gastric cancer and its correlation with the prognosis. Very few studies are there in literature regarding HER2/neu expression in entire gastrointestinal carcinoma. Our study was aimed at HER2/neu expression in gastrointestinal tumors in South Indian Population. M ethods: We included all patients with gastrointestinal carcinoma who either underwent biopsy or surgical excision over the past five years. Slides were reviewed for confirmation of the diagnosis and immunohistochemistry was done using SP3 monoclonal anti-HER2 antibodies. Three independent observers did the scoring for HER2 positivity. Results: Among 35 cases of gastric cancer, only 2 (5.7%) females showed positivity for HER2 scoring and one (2.9%) female showed an equivocal result. All positive and equivocal cases in gastric cancer were intestinal type. Both the cases with HER2 positivity were poorly differentiated tumors. The one with equivocal was a moderately differentiated carcinoma. In colorectal cancer out of 19 cases, only one (5.3%) showed positivity for HER2 whereas in one there was an equivocal response. All the seven cases of small intestinal carcinoma showed negative results for HER2 expression. Conclusion: Overall, HER2/neu expression in gastrointestinal cancer was 4.9%. Female gender, intestinal- type and poorly differentiated cancer showed positivity in gastric cancer. Female gender, left side and low-grade tumor showed positivity in colorectal cancer. Further studies are required with a large sample size to correlate HER2 expression with clinicopathological parameters and its role in prognosis in gastrointestinal carcinomas in the Indian population.References
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27. Overman MJ, Pozadzides J, Kopetz S, Wen S, Abbruzzese J L, Wolff RA et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. British journal of cancer 2010; 102: 144-50.
28. Zhu L, Kim K, Domenico DR, Don R, Hubert E, Appert HE et al. Adenocarcinoma of duodenum and ampulla of Vater: Clinicopathology study and expression of p53, c‐neu, TGF‐α, CEA, and EMA. Journal of surgical oncology 1996; 61: 100-05.
29. Al Haddabi I, Qureshi A, Saparamadu A, Al Hamdani A, Al Riyami M, Ganguly S. Inter-observer agreement in reporting HER 2 Neu protein over expression by immunohistochemistry. Indian Journal of Pathology and Microbiology 2014; 57: 201-04.
2. Elwy DA, Ahmed M, El Aziz A, Samar A, El-Shekh, Ebrahim HA. Immunohistochemical Expression of HER2/neu in Colorectal Carcinoma. Med. J. Cairo Univ 2012; 80: 467-77.
3. Chan OT, Chen ZM, Chung F, Kawachi K, Phan DC, Himmelfarb E et al. Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma. Am J Clin Pathol 2010;134:880-85.
4. Liu L, Wu N, Li J. Novel targeted agents for gastric cancer. J Hematol Oncol 2012; 5: 31-38.
5. Bartley AN, Washington MK, Ventura CB, Ismaila N, Colasacco C, Benson III AB 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. American journal of clinical pathology 2016;146(6):647-69.
6. Siena S, Sartore-Bianchi A, Trusolino L, Martino C, Bencardino K, Lonardi S et al. Therapeutic dual inhibition of HER2 pathway for metastatic colorectal cancer (mCRC): The HERACLES trial. J Clin Oncol 33, 2015 (suppl 3; abstr 565).
7. Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney Cet al. Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. Journal of Clinical Oncology. 2018;36(6):536-44.
8. Hofmann M, Stoss O, Shi D, Buttner 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; 52: 797-805.
9. Ghaffarzadegan K, Sharifi N, Vosooghynia H, Shakeri T, Ghiasi Moghadam T, Kafi SG et al. HER2/neu expression in colon adenocarcinoma an its correlation with clinicopathologic variables. IJBMS 2006;9:64-9.
10. 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. The Lancet. 2010 Aug 28;376:687-97.
11. Ross JS, Mulcahy M. HER2 Testing in Gastric/Gastroesophageal Junction Adenocarcinomas: Unique Features of a Familiar Test. Gastrointest Cancer Res 2012; 4:62–66.
12. Tafe LJ, Janjigian YY, Zaidinski M, Hedvat CV, Hameed MR, Tang LH, et al. Human epidermal growth factor receptor 2 testing in gastresophageal cancer:correlation between immunohistochemistry and fluorescence in situ hybridization. Archives of pathology &laboratory medicine 2011;135:1460-65.
13. Gravalos C, Jimeno A. HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Annals of Oncology 2008; 19: 1523-29.
14. Lordick F, Bang YJ, Kang YK, Reyes DO, Manikhas GM, Shen L, et al. HER2-positive advanced gastric cancer: similar HER2-positivity levels to breast cancer. EJC Supplements. 2007;5:272.
15. 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.
16. He C, Bian XY, Ni XZ, Shen DP, Shen YY, Liu H et al. Correlation of human epidermal growth factor receptor 2 expression with clinicopathological characteristics and prognosis in gastric cancer. World J Gastroenterol 2013;19: 2171-78.
17. Sekaran A, Kandagaddala RS, Darisetty S, Lakhtakia S, Ayyagari S, Rao GV et al. HER2 expression in gastric cancer in Indian population—an immunohistochemistry and fluorescence in situ hybridization study. Indian Journal of Gastroenterology 2012; 31: 106-10.
18. Patil PS, Mehta SA,Mohandas KM. Over-expression of HER2 in Indian patients with gastric cancer. Indian Journal of Gastroenterology 2013; 32: 350.
19. Rajagopal I, Niveditha SR, Sahadev R, Nagappa PK, Rajendra SG. HER 2 Expression in Gastric and Gastro-esophageal Junction (GEJ) Adenocarcinomas. Journal of clinical and diagnostic research 2015; 9: 6-10.
20. Tewari M, Kumar A, Mishra RR, Kumar M, Shukla HS. HER2 expression in gastric and gastroesophageal cancer: report from a tertiary care hospital in North India. Indian Journal of Surgery 2013; 1-5.
21. Schuell B, Gruenberger T, Scheithauer W, Zielinski C, Wrba F. HER 2/neu protein expression in colorectal cancer. BMC Cancer 2006; 6:123-27.
22. Blok EJ, Kuppen PJK, Leeuwen JEM, Sier CFM. Cytoplasmic Overexpression of HER2: a Key Factor in Colorectal Cancer. Oncology 2013;7: 41–51.
23. Half EE, Bresalier RS. Clinical management of hereditary colorectal cancer syndromes. Current opinion in gastroenterology 2004; 20: 32-42.
24. Gruenberger T, Scheithouer W,Zielinski CH,Wrba F. Expression of HER-2/neu in CRC. BMC Cancer 2006; 6: 123-35.
25. McKay JA, Murray LJ, Curran S, Ross VG, Clark C, Murray GI et al. Evaluation of the epidermal growth factor receptor (EGFR) in colorectal tumours and lymph node metastases. European journal of cancer 2002; 38: 2258-64.
26. Deng W, Dong WG, Zhan N, Zhan F, Wu HX. Human epidermal growth factor receptor (HER 2)/neu expression and gene amplification in colorectal cancer. African Journal of Biotechnology 2013; 10: 16732-39.
27. Overman MJ, Pozadzides J, Kopetz S, Wen S, Abbruzzese J L, Wolff RA et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. British journal of cancer 2010; 102: 144-50.
28. Zhu L, Kim K, Domenico DR, Don R, Hubert E, Appert HE et al. Adenocarcinoma of duodenum and ampulla of Vater: Clinicopathology study and expression of p53, c‐neu, TGF‐α, CEA, and EMA. Journal of surgical oncology 1996; 61: 100-05.
29. Al Haddabi I, Qureshi A, Saparamadu A, Al Hamdani A, Al Riyami M, Ganguly S. Inter-observer agreement in reporting HER 2 Neu protein over expression by immunohistochemistry. Indian Journal of Pathology and Microbiology 2014; 57: 201-04.
Published
2020-04-03
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