Overexpression of the HER2/neu Gene: A New Therapeutic Possibility for Patients With Advanced Gallbladder Cancer

Abstract

Background: The HER2/neu gene is a proto-oncogene that can predict the response to treatment with trastuzumab, pertuzumab, and lapatinib. This study was conducted to determine the frequency of HER2/neu overexpression and to identify a subgroup of patients with gallbladder cancer who would benefit from targeted therapy.

Methods: Patients with gallbladder cancer (n = 187; 165 women and 22 men) with a recorded follow-up of at least 5 years were included, along with control subjects (n = 75). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP/ASCO (College of American Pathologists/American Society of Clinical Oncology) criteria for breast cancer.

Results: Overexpression of HER2/neu was observed in 12.8% of the cases. Of those, 0% were mucosal, 14.3% muscular, 12.8% subserosal, and 10.6% serosal. In 20% of the cases, equivocal staining was observed. Overexpression was more frequent in the advanced cancers and in the better differentiated tumors (13.8% and 17.4%, respectively), but the difference was nonsignificant. The patients with overexpression of HER2/neu had a worse overall survival, when compared with those who had no expression at 5 years (34% vs. 41%).

Conclusion: This is the single largest study of HER2/neu expression in gallbladder cancer to use commonly accepted scoring criteria. The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases. This subgroup may benefit from inhibitors of the HER2/neu pathway.

Figure 1.

HER2/neu immunohistochemical staining: (A) focal, weak (1+) positivity in the superficial area of the mucosa in pyloric metaplasia; (B) positive basolateral membrane staining (2+) in intestinal metaplasia; and (C, D) gallbladder adenocarcinoma with strong membrane-positive staining (+3) in more than 30% of the tumor cells.

Figure 2.

Top: actuarial survival of the total group according to the level of tumor infiltration of the gallbladder wall; bottom: survival curves in patients with (positive) and without (negative) HER2 overexpression. Patients with overexpression had a worse survival rate; however, the difference was not significant.