Evaluation of Microsatellite Instability and Apoptosis in Gall Bladder Malignancy from Patients of a Cohort Exposed to Methylisocyanate

Abstract

The molecular alterations are considered to play an important role in the both carcinogenesis and biological behavior of a variety of human malignancies. However, cancer of gallbladder is an obscured phenomenon and highly malignant with a poor survival due to underprivileged diagnosis. Tissues of 92 cases of gallbladder cancer patients (31 men and 61 women, age range 16-85 yrs, mean age 45.83 ± 1.50 yrs) were examined for microsatellite instability (MSI) of six microsatellite markers (D16S539, D13S317, D7S820, F13A01, FES/FPS, vWA) and apoptosis of malignant epithelial cells through M30CytoDEATH assay. Analysis of microsatellite markers revealed 08.7% (08/92) in gallbladder cancer, in which 10.0% (07/70) instability found in adenocarcinoma. The sensitivity of this test in adenocarcinoma, adenosquamous carcinaoma and adenoma with dysplasia was found to be 10.0%, 00.0% and 08.3% respectively suggesting its role in the multistage disease invasiveness. The immunohistochemical examination confirmed the presence of CK18 in moderately, well and poorly differentiated adenocarcinoma with the frequency of viz., 18.8%, 15.4% and 11.1% respectively showing positive sign of apoptosis. The mixed chimerism of STR loci and positive staining of caspase cleaved CK18 in epithelial cells of the gallbladder cancer tissues showed their independent and noteworthy character in the gallbladder carcinogenesis. Further investigations are in progress to undertake similar studies on archived tumor tissues of varied origins and forms. These might also provide modalities to translate forceful and reproducible strategies for defined clinical utility.