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 colorectal cancers, and the purpose of this study was to investigate whether the proliferative activity of fibroblasts and endothelial cells plays an important role in tumor progression of T3 ulcerative-type colorectal cancer. The tumor area of 157 colorectal cancers was divided into marginal elevated area and central depressed area (CDA), and at half the depth of the depression the CDA was in turn divided into CDA upper area (CDAU) and CDA lower 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 estimated as the percentage of microvessels lined by MIB-1-positive endothelial cells relative to the total microvessel count. Proliferative activities of tumor cells showed significant associations with those of fibroblasts and the proliferative microvessel indices in all of the corresponding areas. Proliferative activities of fibroblasts also showed significant associations with proliferative microvessel indices in all of the corresponding areas. Colorectal cancers with nodal metastasis showed significantly higher proliferative activities of fibroblasts in the CDAU than those without nodal metastasis (P <.001). The high proliferative activities of fibroblasts and proliferative microvessel indices in the CDAU showed significant associations with short distant organ metastasis-free periods in colorectal cancers without 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 patients with nodal metastasis (P =.018). Proliferative activities of fibroblasts and endothelial cells in the CDAU are useful parameters for predicting tumor metastasis in patients with T3 ulcerative-type colorectal cancer. HUM PATHOL 32:401-409.

The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis.

A fibrotic focus (FF) is a clearly defined area consisting of fibroblasts and/or collagen fibres arranged in irregular or storiform patterns within tumours. We looked to see whether FF in advanced colorectal carcinoma was associated with distant organ metastasis especially to the liver. The correlation between FF and the presence of synchronous or total (synchronous and/or metachronous) liver metastasis and tumour recurrence was assessed in 77 patients with Dukes B and C advanced colorectal carcinoma treated by resection. The median follow-up period was 21 months. In multivariate analysis, FF significantly increased the relative risk (RR) of synchronous liver metastasis (RR=4.9, P<0.05) and total liver metastasis (RR=4.6, P<0.05). FF also increased the RR of tumour recurrence (RR=2.4), but the increase was not statistically significant. FF is a newly recognized histological indicator of liver metastasis in advanced colorectal carcinoma.

Tumor thickness is a histopathologic predictive parameter of tumor metastasis and prognosis in patients with Dukes stage C ulcerative-type colorectal carcinoma. A two-hospital-based study.

BACKGROUND: Metastasis to the liver or lymph nodes is an important prognostic factor in patients with colorectal carcinoma. The purpose of the current study was to estimate the power of tumor thickness in predicting metachronous liver metastasis (MLM), lymph node metastasis (LNM), or overall survival (OS) in patients at two hospitals (the National Cancer Center Hospital [NCCH] and the National Cancer Center Hospital East [NCCHE]) to confirm the reproducibility of the study. METHODS: The subjects of this study were 74 and 186 consecutive patients with ulcerative-type colorectal carcinoma treated at the NCCH and NCCHE, respectively. Tumor thickness was measured in three areas: 1) the marginal elevated area (MEA), 2) the central depressed area (CDA), and 3) the most thickened area (MTA). Studies were performed with well known histologic parameters to compare the predictive power of tumor thickness on MLM, LNM, and OS using the Cox proportional hazards regression model or analysis of variance. RESULTS: A significant correlation between tumor thickness and MLM was observed only in the CDA in the NCCH patients (P = 0.005). The authors applied a tumor thickness cutoff value in the CDA of 10 mm ( 10 mm) for further study. Multivariate analyses demonstrated that a tumor CDA thickness > 10 mm was associated significantly with MLM, multiple LNMs, and OS in NCCH patients with Dukes Stage C disease (P = 0.002, P = 0.023, and P = 0.002, respectively). A significant predictive power for tumor CDA thickness for MLM, multiple LNMs, and OS was confirmed by multivariate analysis in NCCHE patients with Dukes Stage C disease (P = 0.008, P = 0.021, and P = 0.010, respectively). CONCLUSIONS: The CDA thickness of the tumor was found to be a useful predictive parameter for MLM, multiple LNMs, and OS in patients with Dukes Stage C ulcerative-type colorectal carcinoma who were being treated in two independent hospitals.