Detection of ras oncogene point mutations and simultaneous proliferative fraction estimation in gallbladder cancer

Gallbladder cancer is notorious for its poor clinical evolution; so, a study of parameters with any prognostic potential is of particular interest. In this study, we investigated 23 adenocarcinomas regarding both the presence of point mutations in the ras gene family and the quantitative expression of Proliferating Cell Nuclear Antigen (PCNA). We respectively used molecular biology techniques and immunohistochemistry. Our results were related to several clinicopathologic determinators as well as to patients' survival. Mutations in codon 12 of the K-ras gene were detected in four gallbladder neoplasms (17%). This specific type of mutation is likely to be partially involved in this organ's tumourigenesis, particularly since no H-ras codon 12 or K-ras codon 13 (aspartic acid) mutations were detected in any of our specimens. PCNA immunoreactivity was generally limited in all tumours studied except for those morphologically characterized as being particularly aggressive. Notably, the four tumours in which K-ras mutation was detected, demonstrated relatively high PCNA positive immunoexpression in their malignant cells. This finding reinforces a possible correlation between the presence of ras mutations and increased cell growth. Staging was the only factor which was statistically associated with survival (p < 0.01). Therefore, the poor evolution of this cancer is probably due to late diagnosis and not related to a model of increased biologic aggressiveness.