Gallbladder Adenocarcinoma, Potential Target for Anti-Her-2 Therapy
Her-2 (ErbB-2) is an oncogene frequently overexpressed in breast and gastric adenocarcinomas, and anti-Her-2 targeted therapy can be given to such patients. Her-2 overexpression and role of anti-Her-2 targeted therapy in cases of gallbladder adenocarcinomas (GBC) are still debatable. Scoring protocols for Her-2 expression in breast and gastric carcinomas are standardized, however, not for carcinomas arising in other body organs like the gallbladder. This study is conducted to evaluate the expression of Her-2 in patients with GBC, which may benefit from targeted therapy. It is a cross-sectional study conducted on patients with GBC (n=63; 53 women and ten men). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP (College of American Pathologists) criteria for breast cancer. Positive (3+) Her-2 staining was observed in 8/63 (12.7%). Nine cases (14.3%) showed equivocal staining (2+) pattern. All of the tumors showing Her-2 overexpression were moderately differentiated. This study indicates that a significant number of GBC cases show Her-2 overexpression. This subgroup may benefit from inhibitors of the Her-2 pathway. Standardization of scoring protocol for Her-2 expression in GBC is needed to better evaluate the predictive potential of Her-2 for the treatment of these tumors.
2. Alvi AR, Siddiqui NA, Zafar H. Risk factors of gallbladder cancer in Karachi-a case-control study. World J of surg oncol. 2011 Dec 9;9(1):1.
3. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer worldwide: geographical distribution and risk factors. Int J cancer. 2006 Apr 1;118(7):1591-602.
4. Dutta U. Gallbladder cancer: Can newer insights improve the outcome? J gastroenterol hepatol. 2012 Apr 1;27(4):642-53.
5. Goetze TO. Gallbladder carcinoma: Prognostic factors and therapeutic options. World J Gastroenterol. 2015 Nov 21;21(43):12211.
6. Andrén-Sandberg Å. Diagnosis and management of gallbladder cancer. North American journal of medical sciences. 2012 Jul 1;4(7):293.
7. Tsilidis KK, Kasimis JC, Lopez DS, Ntzani EE, Ioannidis JP. Type 2 diabetes and cancer: umbrella review of meta-analyses of observational studies. Bmj. 2015 Jan 2;350:g7607.
8. Hemminki K, Li X, Sundquist J, Sundquist K. Obesity and familial obesity and risk of cancer. European Journal of Cancer Prevention. 2011 Sep 1;20(5):438-43.
9. Kanthan R, Senger JL, Ahmed S, Kanthan SC. Gallbladder cancer in the 21st century. Journal of oncology. 2015 Sep 1;2015.
10. Chua TC, Merrett ND. Clinicopathologic factors associated with HER2‐positive gastric cancer and its impact on survival outcomes—A systematic review. International Journal of Cancer. 2012 Jun 15;130(12):2845-56.
11. English DP, Roque DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Molecular diagnosis & therapy. 2013 Apr 1;17(2):85-99.
12. Grillo F, Fassan M, Sarocchi F, Fiocca R, Mastracci L. HER2 heterogeneity in gastric/gastroesophageal cancers: From benchside to practice. World Journal of Gastroenterology. 2016 Jul 14;22(26):5879.
13. Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014 Jan 1;17(1):1-2.
14. Roa I, de Toro G, Schalper K, de Aretxabala X, Churi C, Javle M. Overexpression of the HER2/neu gene: a new therapeutic possibility for patients with advanced gallbladder cancer. Gastrointestinal cancer research: GCR. 2014 Mar;7(2):42.
15. Kaufman M, Mehrotra B, Limaye S, White S, Fuchs A, Lebowicz Y, Nissel-Horowitz S, Thomas A. EGFR expression in gallbladder carcinoma in North America. Int J Med Sci. 2008 Sep 22;5(5):285-91.
16. Ashai F, Ashraf A, Rashid A, Banday BM, Bhalla S, Dhawan S. Expression of Her2/neu receptor in carcinoma gallbladder correlates significantly with advanced tumor stage. Int J Hepatobiliary Pancreat Dis. 2015 Dec 1;5:86-91.
17. Koshiol J, Gao YT, Dean M, et al. Association of Aflatoxin and Gallbladder Cancer. Gastroenterol 2017; 153:488. (Drugs)
18. Wolff AC, Hammond ME, Schwartz JN et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arc Pathol & Lab Med. 2007 Jan; 131(1):18-43.
19. Kiguchi K, Carbajal S, Chan K, et al. Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma. Cancer Res 2001;61:6971-6
20. Lam JY, Choo SP, Teh BT. HER2 as a therapeutic target in gallbladder cancer—aye or nay?. Translational Cancer Res. 2016 Jan 29;5(1):7-10.
21. Kawamoto T, Krishnamurthy S, Tarco E, et al. HER Receptor Family: Novel Candidate for Targeted Therapy for Gallbladder and Extrahepatic Bile Duct Cancer. Gastrointest Cancer Res. 2007 Nov;1(6):221–7
22. Suzuki T, Takano Y, Kakita A, Okudaira M. An immunohistochemical and molecular biological study of c-erbB-2 amplification and prognostic relevance in gallbladder cancer. Pathol Res Pract 1993 Apr;189(3):283–92.
23. Kim YW, Huh SH, Park YK, Yoon TY, Lee SM, Hong SH. Expression of the c-erb-B2 and p53 protein in gallbladder carcinomas. Oncol Rep 2001 Sep-Oct;8(5):1127–32.
24. Yao M, Fu P. Advances in anti-HER2 therapy in metastatic breast cancer. Chinese clinical oncology. 2018 Jun 25;7(3).
25. Ung L, Chua TC, Merrett ND. Targeting HER2 amplifications in gastric cancer. Gastrointestinal Cancer: Targets and Therapy. 2014;4:11-22.
26. Kiguchi K, Ruffino L, Kawamoto T, et al. Chemopreventive and therapeutic efficacy of orally active tyrosine kinase inhibitors in a transgenic mouse model of gallbladder carcinoma. Clin Cancer Res 2005;11:5572-80
27. Pignochino Y, Sarotto I, Peraldo-Neia C, et al. Targeting EGFR/HER2 pathways enhances the antiproliferative effect of gemcitabine in biliary tract and gallbladder carcinomas. BMC Cancer 2010;10:631.
28. Javle M, Churi C, Kang HC, et al. HER2/neu-directed therapy for biliary tract cancer. J Hematol Oncol 2015;8:58.
29. Trastuzumab in Treating Patients With Locally Advanced or Metastatic Gallbladder Cancer or Bile Duct Cancer That Cannot Be Removed by Surgery, 28 May 2014, (https://clinicaltrials.gov/ct2/show/results/NCT00478140).
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