Back to Program | 2010 Program and Abstracts Overview | 2010 Posters

Background: Gallbladder cancer (CAGB) is a concealed phenomenon and highly malignant with a poor survival rate thought to be driven by the accumulation of genetic alterations and consequent changes in gene expression patterns. Study of cancer patterns amongst victims of Bhopal gas tragedy exposed to methyl isocyanate (MIC) revealed higher incidence of CAGB. This necessitated an objective elucidation of the molecular changes in CAGB. Objectives: To study the expression patterns of p53, Rad50, cyclin-E, k-ras with mixed chimerism of STR loci in a cohort exposed to MIC diagnosed with CAGB. Materials and Methods: Surgical resected specimens of 40 cases of patients (13 men and 27 women, age range 20-75 yrs, mean age 55.25 ± 1.89 yrs) with 31 adenocarcinoma (07 well differentiated, 19 moderately differentiated and 05 poorly differentiated), 03 adenosquamous carcinoma and 06 gallbladder adenoma were examined for p53, Rad50, cyclin-E, k-ras through immune-histofluorescence using spectral bio-imaging system. Microsatellite instability was determined from PCR amplifications of six-microsatellite markers (D16S539, D13S317, D7S820, F13A01, FESFPS, vWA).Results: Of the 40 samples, 74%, 35%, 32% and 38% showed positivity for p53, Rad50, cyclin-E and K-ras expression respectively in adenocarcinomas (p=0.0001) and in adenosquamous cell carcinoma the positivity of mutations for above four genes are 33.3%, 33.3%, 0.00% and 50% respectively (p=0.0069) suggesting the prevalence and invasiveness of the disease. However, co-expression of k-ras, Rad 50 and cyclin-E with p53 was absent in adenomas with dysplasia implicating their independent role. Microsatellite instability results determined by the multiplex STR PCR also showed statistical significant relationships independent with tumor type and stage.Conclusions: These results imply that the expressions of p53, Rad50, cyclin-E and K-ras are altered along with mixed chimerism of STR loci. The identification of genes and pathways involved in gall bladder carcinogenesis will not only enhance our understanding of the biology of this process but will simultaneously provide new targets for early diagnosis and facilitate novel embattled treatment design for CAGB.