Gall bladder carcinomas (GBC) are one of the most common and aggressive biliary tract malignancies causing significant mortality in South-East Asia and South America as a result of advanced stage at presentation, early metastases, and poor outcomes with standard chemotherapy. Overexpression of Her2/Neu is associated with poor prognosis in breast and gastric carcinomas, which is also being studied for GBC. Ki 67 proliferation index, a marker of replicative potential, is high in higher-grade and aggressive tumors. The aim was to study the expression of Her2/neu and Ki 67 by immunohistochemistry (IHC) in GBC and it's correlation with clinicopathologic parameters.
This was a retrospective study conducted in the Department of Pathology at a tertiary cancer center of North India, from May 2018 to December 2019 wherein all the cases of GBC were retrieved along with their relevant clinical and radiological data. IHC for Her2/Neu and Ki 67 was performed and analyzed.
Out of 133 cases of GBC, mean age was 54.1 years, with female predominance (70%, 93 cases). The most common histology was adenocarcinoma (94%), most of which were moderately differentiated (40.6%). Positive Her2/Neu expression (score 3+) was found in 31 cases (23.4%) while 76 cases (57.1%) were negative (score 0 to 1). Her2/Neu expression was significantly lost as the grade of the tumor increased which was statistically significant (p-value <0.05). Percentage positivity of Her2/Neu in stages I, II, III, and IV was 33%, 12%, 40%, and 22% respectively. Her2/Neu overexpression did not correlate with lymph node or distant metastasis. Ki 67 proliferation index ranged from 5% to 99% in the tumors (mean- 65.3%) which increased with increasing grade.
Her2/Neu overexpression is seen in a fair number of stage II and III patients, where it may serve as a target for adjuvant therapy. In stage IV patients, 22% positivity of Her2/neu represents an opportunity to provide meaningful clinical benefit by the addition of anti-Her2 therapy. However, further studies in these settings are warranted to establish the role of Her2/Neu as a predictive and prognostic marker in GBC.
The authors.
Intramural funding, HBCH/MPMMCC, Varanasi.
All authors have declared no conflicts of interest.