Highly proliferative intratumoral fibroblasts and a high proliferative microvessel index are significant predictors of tumor metastasis in T3 ulcerative-type colorectal cancer

Fibroblast and endothelial cell mitotic figures are seen in some areas of c olorectal cancers, and the purpose of this study was to investigate whether the proliferative activity of fibroblasts and endothelial cells plays an i mportant role hr turner progression of T3 ulcerative-type colorectal cancer . The tumor area of 157 colorectal cancers was divided into marginal elevat ed area and central depressed area (CDA), and at half the depth of the depr ession the CDA was in turn divided into CDA upper al ea (CDAU) and CDA lowe r area (CDAL). The proliferative activity of the tumor cells, fibroblasts, and endothelial cells was assessed immunohistochemically by double CD31/MIB -1 (anti-Ki-67 antigen) staining. The proliferative microvessel index was e stimated as the percentage of microvessels lined by MIB-1-positive endothel ial cells relative to the total microvessel count. Proliferative activities of tumor cells showed significant associations with those of fibroblasts a nd die proliferative microvessel indices in all of the corresponding areas. Proliferative activities of fibroblasts also showed significant associatio ns with proliferative microvessel indices in all of the corresponding areas . Colorectal cancers with nodal metastasis showed significantly higher prol iferative activities of fibroblasts in the CDAU than those without nodal me tastasis (P < .001). nle high proliferative activities of fibroblasts and p roliferative microvessel indices in the CDAU showed significant association s with short distant organ metastasis-free periods in colorectal cancers wi thout nodal metastasis (P < .001 and P =.010, respectively) and those with nodal metastasis (P =.024 and P =.036, respectively). Multivariate analysis showed that the highly proliferative fibroblasts in the CDAU significantly increased hazard rates of distant organ metastasis of colorectal cancer pa tients with nodal metastasis (P =.018). Proliferative activities of fibrobl asts and endothelial cells in the CDAU are useful parameters for predicting tumor metastasis: in patients with T3 ulcerative-type colorectal cancer.