The Prognostic Significance of Chromosome 18 Monosomy in the Colon Cancer: Correlations with the Expressions of Smad4 and TGF-beta Receptor II Proteins

ABSTRACT

PURPOSE: Chromosomal instability of chromosome 18 and inhibition of the transforming growth factor beta (TGF-beta) signaling pathway, which is mediated through Smad4, play important roles in the tumorigenesis of colon cancer. This study evaluated the value of the expression of chromosome 18 monosomy in colon cancer as a prognostic factor and its correlations with the expressions of Smad4 and TGF-beta receptor II proteins. METHODS: We analyzed the rate of the expression of chromosome 18 monosomy in 66 colon cancers with using chromogenic in situ hybridization (CISH) and we evaluated its value as a prognostic factor by determining its correlation with the pathologic factors and immunohistochemical expressions of Smad4 and TGF-beta receptor II proteins. RESULTS: Of the 66 colon cancers, monosomy of chromosome 18, as determined by CISH, was observed in 18 cases (27.3%), and the decreased expression of Smad4 and TGF-beta receptor II proteins was observed in 30 cases (45.5%) and 25 cases (37.9%), respectively. The monosomy of chromosome 18 and the decreased expression of Smad4 proteins showed statistically significant correlations with the histologic differentiation, the presence of tumor emboli, the nodal status and the stage. The decreased expression of TGF-beta receptor II proteins had statistically significant correlations with the histologic differentiation, the T-stage, the nodal status and the stage. The monosomy of chromosome 18 showed a statistically significant correlation with the decreased expression of Smad4 and TGF-beta receptor II proteins. CONCLUSION: These results suggested that chromosome 18 monosomy may have prognostic value for colon cancer.