G protein γ7 expression as a new clinicopathological marker in patients with intrahepatic cholangiocarcinoma

Hypothesis: The signal alterations mediated by small G proteins such as Ras, Rho, and Rac have been reported in several cancers. The human G protein γ7 (G-γ7) gene, which is down-regulated in various digestive organ cancers, was recently identified and cloned. Thus, the G-γ7-coupled heterotrimeric G proteins may also contribute to carcinogenesis in human cancers. Setting: University hospital and medical institute of bioregulation. Patients and Methods: The clinicopathological significance of G-γ7 expression in 18 patients with intrahepatic cholangiocarcinoma (IHCC) was examined. The tumor-nontumor ratio of G-γ7 expression was determined using reverse transcription polymerase chain reaction analysis. To visualize the localization of G-γ7, an immunohistochemical study was performed. Main Outcome Measure: Clinicopathological significance of G-γ7 expression in human IHCC. Results: Expression of G-γ7 messenger RNA was lower in tumor tissue than in the corresponding nontumor tissue in 17 (94%) of 18 patients with IHCC. The mean tumor-nontumor ratio was 0.54. Eleven patients with tumor-nontumor ratios less than 0.5 showed significantly poorer differentiated IHCC than 7 with tumor-nontumor ratios of 0.5 and greater (P<.01). Decreased expression of G-γ7 protein in the carcinoma tissue, especially in the poorly differentiated IHCC tissue, was confirmed using immunohistochemical staining. Conclusions: Reduced expression of G-γ7 is associated with the histological grade of IHCC and may therefore prove to be a useful marker for predicting the biological aggressiveness of human IHCC.