Role of EGFR and HER-2/NEU Expression in Gall Bladder Carcinoma (GBC)Funding Nil.
Background Gall bladder carcinoma (GBC) is the most common malignancy of the biliary tract. Being known for its geographical and racial variations, and compared with the global statistics, its incidence is higher in the Indian subcontinent, mainly in the northern and eastern regions, accounting for 80 to 95% of cases.
Aims and Objectives This study was conducted to evaluate the clinic-pathological spectrum and expression of EGFR and HER-2/NEU in GBCs and to understand their relation to prognosis, paving the way for targeted therapies for better treatment outcomes and patient survival.
Materials and Methods This is a prospective study performed in a tertiary care hospital in 30 resected specimens of GBC cases recorded in our Department of Pathology from November 2017 to November 2019. Clinical history including the radiological reports and demographic parameters were included in the study pro forma. Immunohistochemical (IHC) staining for EGFR and HER-2/NEU was performed on all the selected cases. Clinicopathologic parameters like age, sex, histologic type, perineural, and lymphovascular invasion were compared and correlated with EGFR and HER-2/NEU status.
Results Expression of EGFR was found in 93.33% of cases, which showed a highly significant correlation with histological tumor type (p = 0.000). HER-2/NEU expression was found in 56.66% of cases, which also showed a significant correlation with histological tumour type (p = 0.021). We found most of the cases with strong EGFR immunoreactivity (3+) were poorly differentiated tumors and most of the cases showing weak immunoreactivity for EGFR (1+) were well-differentiated. Conversely, in case of HER-2/NEU immunoreactivity, strong staining (3+) was seen in well-differentiated tumors and weak staining (1+) in poorly differentiated tumors. A significant correlation was also found between EGFR and HER-2/NEU expression (p = 0.000) and between cholelithiasis and EGFR expression (p = 0.033).
Conclusion EGFR is expressed in most cases of GBC. Its expression is more in poorly differentiated carcinomas as compared to the well-differentiated carcinomas, whereas HER-2/NEU expression is more in well-differentiated carcinomas. Therefore, they may serve as independent prognostic factors and also as targets for molecular therapy in GBCs.
19. Mai 2021 (online)
© 2021. The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India
- 1 Hundal R, Shaffer EA. Gallbladder cancer: epidemiology and outcome. Clin Epidemiol 2014; 6: 99-109
- 2 International Agency for Research on Cancer. GLOBOCAN v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Available at: http://globocan.iarc.fr/old/summary_table_site-html.asp?selection=7080&title=Gallbladder&sex=0&type=0&window=1&africa=1&america=2&asia=3&europe=4&oceania=5&build=6&sort=0&submitted. Accessed September 16, 2020
- 3 Wistuba II, Gazdar AF. Gallbladder cancer: lessons from a rare tumour. Nat Rev Cancer 2004; 4 (09) 695-706
- 4 Valle J, Wasan H, Palmer DH. et al; ABC-02 Trial Investigators. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010; 362 (14) 1273-1281
- 5 Zhou YM, Li YM, Cao N, Feng Y, Zeng F. [Significance of expression of epidermal growth factor (EGF) and its receptor (EGFR) in chronic cholecystitis and gallbladder carcinoma]. Chin J Cancer 2003; 22 (03) 262-265
- 6 Ariyama H, Qin B, Baba E. et al. Gefitinib, a selective EGFR tyrosine kinase inhibitor, induces apoptosis through activation of Bax in human gallbladder adenocarcinoma cells. J Cell Biochem 2006; 97 (04) 724-734
- 7 Nakazawa K, Dobashi Y, Suzuki S, Fujii H, Takeda Y, Ooi A. Amplification and overexpression of c-erbB-2, epidermal growth factor receptor, and c-met in biliary tract cancers. J Pathol 2005; 206 (03) 356-365
- 8 Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol 2005; 23 (11) 2445-2459
- 9 Chow NH, Huang SM, Chan SH, Mo LR, Hwang MH, Su WC. Significance of c-erbB-2 expression in normal and neoplastic epithelium of biliary tract. Anticancer Res 1995; 15 (03) 1055-1059
- 10 Kim CH, Kim SH, Park SY, Yoo J, Kim SK, Kim HK. Identification of EGFR mutations by immunohistochemistry with egfr mutation-specific antibodies in biopsy and resection specimens from pulmonary adenocarcinoma. Cancer Res Treat 2015; 47 (04) 653-660
- 11 Wolff AC, Hammond ME, Hicks DG. et al; American Society of Clinical Oncology; College of American Pathologists. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. Arch Pathol Lab Med 2014; 138 (02) 241-256
- 12 Kapoor VK, McMichael AJ. Gallbladder cancer: an ‘Indian’ disease. Natl Med J India 2003; 16 (04) 209-213
- 13 Shukla VK, Khandelwal C, Roy SK, Vaidya MP. Primary carcinoma of the gall bladder: a review of a 16-year period at the University Hospital. J Surg Oncol 1985; 28 (01) 32-35
- 14 Pandey M, Pathak AK, Gautam A, Aryya NC, Shukla VK. Carcinoma of the gallbladder: a retrospective review of 99 cases. Dig Dis Sci 2001; 46 (06) 1145-1151
- 15 Chijiiwa K, Nakano K, Ueda J. et al. Surgical treatment of patients with T2 gallbladder carcinoma invading the subserosal layer. J Am Coll Surg 2001; 192 (05) 600-607
- 16 Ahmad M, Attoub S, Singh MN, Martin FL, El-Agnaf OM. Gamma-synuclein and the progression of cancer. FASEB J 2007; 21 (13) 3419-3430
- 17 Hadi R, Singhal A, Masood S, Awasthi NP. Expression of Erb-B1 and Erb-B2 in cholecystectomy specimen done for benign gall bladder disease. World Journal of Surgical Medical and Radiation Oncology 2014; 8: 44-49
- 18 Sergeant G, Lerut E, Ectors N, Hendrickx T, Aerts R, Topal B. The prognostic relevance of tumor hypoxia markers in resected carcinoma of the gallbladder. Eur J Surg Oncol 2011; 37 (01) 80-86
- 19 Lubner SJ, Mahoney MR, Kolesar JL. et al. Report of a multicenter phase II trial testing a combination of biweekly bevacizumab and daily erlotinib in patients with unresectable biliary cancer: a phase II Consortium study. J Clin Oncol 2010; 28 (21) 3491-3497
- 20 Philip PA, Mahoney MR, Allmer C. et al. Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol 2006; 24 (19) 3069-3074
- 21 Chiorean EG, Ramasubbaiah R, Yu M. et al. Phase II trial of erlotinib and docetaxel in advanced and refractory hepatocellular and biliary cancers: Hoosier Oncology Group GI06-101. Oncologist 2012; 17 (01) 13
- 22 Lee CS, Pirdas A. Epidermal growth factor receptor immunoreactivity in gallbladder and extrahepatic biliary tract tumours. Pathol Res Pract 1995; 191 (11) 1087-1091
- 23 Kaufman M, Mehrotra B, Limaye S. et al. EGFR expression in gallbladder carcinoma in North America. Int J Med Sci 2008; 5 (05) 285-291
- 24 Viswanath S, Bhardwaj R, Kapoor A. Clinicopathological significance of epidermal growth factor receptor and vascular endothelial growth factor expression in biliary tract malignancies. J NTR Univ Health Sci 2017; 6: 82-85
- 25 Shafizadeh N, Grenert JP, Sahai V, Kakar S. Epidermal growth factor receptor and HER-2/neu status by immunohistochemistry and fluorescence in situ hybridization in adenocarcinomas of the biliary tree and gallbladder. Hum Pathol 2010; 41 (04) 485-492
- 26 Maurya SK, Tewari M, Mishra RR, Shukla HS. Genetic aberrations in gallbladder cancer. Surg Oncol 2012; 21 (01) 37-43
- 27 Müller BG, De Aretxabala X, González Domingo M. A review of recent data in the treatment of gallbladder cancer: what we know, what we do, and what should be done. Am Soc Clin Oncol Educ Book 2014; e-pub ahead of print. doi: https://doi.org/10.14694/edbook_am.2014.34. e165
- 28 Javle M, Churi C, Kang HC. et al. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol 2015; 8: 58
- 29 Yoshida H, Shimada K, Kosuge T, Hiraoka N. A significant subgroup of resectable gallbladder cancer patients has an HER2 positive status. Virchows Arch 2016; 468 (04) 431-439
- 30 Kiguchi K, Ruffino L, Kawamoto T, Ajiki T, Digiovanni J. Chemopreventive and therapeutic efficacy of orally active tyrosine kinase inhibitors in a transgenic mouse model of gallbladder carcinoma. Clin Cancer Res 2005; 11 (15) 5572-5580