జర్నల్ ఆఫ్ ఆంకాలజీ అనువాద పరిశోధన

Clinicopathological and Cyclin D1, E-cadherin, EGFR, HER- 2, Ki67, and p53 immunomarkers correlation in Gall bladder cancer cases and its precursor lesions

Abstract

Anshoo Agarwal

Background:

The Indian Council of Medical Research in India has reflected that the occurrence of Gall bladder carcinoma (GBC) is predominantly higher in northern India. Reports from ICMR suggests that the incidence of GBC corresponds to 3.6 per million in males and 7.4 per million in females in Delhi, India, as compared to 1.13 per million in the US. The incidence is high in females and it represent almost three fourths of GBC victims and their highest incidence rate occur in this region, yet only few immunomarker studies are available from this high-predisposing region. GBC has also been reported to show a variable expression pattern among different ethnic groups. GBC results via the dysplasia-metaplasia sequence and the 5-year survival rate for GBC is 32% and for the advanced stage it is only 10%. Current studies have focused on the importance of Cyclin D1, E-cadherin, EGFR, HER-2, Ki67, and p53 immunomarkers in the development and prognosis of GBC. One of the most genetic aberrations is ascribed to be HER-2 in GBC. HER-2 and other immunomarkers Cyclin D1, E-cadherin, EGFR, Ki67, and p53 can be easily assessed by standard immunohistochemistry methods. However, concrete results have not been obtained due to a limited number of respectable GBC cases presented at the hospitals. We, therefore, attempt to evaluate the immune-expression of these markers in GBC cases and determine their prognostic value in the selected GBC cohort.

Material and Methods:

30 resected GBC cases were collected from the Gall bladder lesion cases. Histological type, and differentiation grading of all specimens was obtained from H&E-stained slides. Immunohistochemistry Formalin-fixed (10%), paraffin-embedded GBC were sectioned (3–5 μm thick) and were treated with ready-to-use monoclonal antibodies Cyclin D1, E-cadherin, EGFR, HER- 2, Ki67, and p53 c-erbB-2 of (Dako® Corporation, Carpinteria, Calif., USA) were used as the primary antibody. Scoring was based on the Herceptest TM (Dako) criteria; semi-quantitative analysis of the stain intensity was carried out. The number of Immunomarker-stained cells in representative microscopic fields was counted.

Results:

The average age of the patient cohort was 53 years, and 55% of them were females. 62% of cases had gallstones of different sizes and the average tumor size was 45 mm. All the cases were mostly histologically proved to be adenocarcinoma. About 11/30 of the patients showed staining for HER-2 , and 10/30 of the tumor cases showed positivity for p53, 14/30 of the tumor cases showed positivity for Cyclin D1,12/30 of the tumor cases showed positivity for E-cadherin, 113/30 of the tumor cases showed positivity for EGFR, and 17 /30 of the tumor cases showed positivity for Ki67 .Contingency table analysis by χ2 tests showed that HER-2, Cyclin D1, E-cadherin, EGFR, positivity showed significance with sex (p = 0.02). On the other hand, Ki67, and p53-positive cases did not show any significance with clinicopathological factors. HER-2, Cyclin D1, E-cadherin, EGFR, Ki67, and p53 showed statistical significance. Hence their expressions are considered to be significant prognostic factors in the selected GBC cohort.

Conclusions:

Consequently, it can be summed up that there is an important need to search for immuno- markers of GBC, which will not only diagnose and prognosticate the disease but also help in choosing the appropriate mode of therapy and may give us an opportunity to make our basic understanding of GBC pathology clearer. Thus, our study assesses the expression of important immunomarkers involved in the pathogenesis of GBC, correlates it with clinicopathological parameters and establishes it as an independent prognostic factor in GBC.