Gallbladder Adenocarcinoma, Potential Target for Anti-Her-2 Therapy
,
Abstract
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.
1. Lazcano‐Ponce EC, Miquel JF, Muñoz N, Herrero R, Ferrecio C, Wistuba II, de Ruiz PA, Urista GA, Nervi F. Epidemiology and molecular pathology of gallbladder cancer. CA: A Cancer J for Clinicians. 2001 Nov 1;51(6):349-64.
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).
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).
| Files | ||
| Issue | Vol 58, No 5 (2020) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/acta.v58i5.3957 | |
| Keywords | ||
| Gallbladder Adenocarcinoma Human epidermal growth factor receptor 2 (Her-2) | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Zafar G, Afzal S, Zafar A, Zaman S. Gallbladder Adenocarcinoma, Potential Target for Anti-Her-2 Therapy. Acta Med Iran. 2020;58(5):234-239.
