Nuclear beta-catenin accumulation as a prognostic factor in Dukes' D human colorectal cancers.

Beta-catenin is well recognized to play a crucial role as a transcriptional factor during the early step of colorectal carcinogenesis. Some reports concerning the clinical implications of cytoplasmic and/or nuclear beta-catenin accumulation are available, though their results vary. On the other hand, the clinical implication of nuclear accumulation of beta-catenin in Dukes' D colorectal cancers (with distant metastasis) has not been investigated. To assess its value as a prognostic marker in this stage, we selected the cases with synchronous liver metastasis. Thirty-eight surgically resected primary and corresponding metastatic liver tumors were examined immunohistochemically and the relationships between nuclear beta-catenin accumulation and clinicopathological variables were analyzed. Of the 38 primary colorectal cancers analyzed, 11 (29%) showed nuclear accumulation of beta-catenin with cytoplasmic staining. Nuclear accumulation positivity was more frequently associated with lymph node metastasis than being negative [100% (11/11) vs. 67% (18/27), p=0.04]. There was a significant difference in median survival time between the nuclear beta-catenin positive group (1130 days) and the negative group (2102 days: p=0.037). Interestingly, all of the patients (9/9) in the former group had died when the recurrence was in the liver, while 42% (8/19) in the latter group had survived even if the recurrence was in the liver (p=0.03). In conclusion, though these results were obtained in a small series of patients, nuclear accumulation of beta-catenin may be a useful prognostic marker even in Dukes' D colorectal cancers.

Proliferative activities of tumor stromal cells play important roles in tumor thickness and progression of T3 ulcerative-type colorectal cancer.

The central depressed area thickness (tumor thickness) of colorectal cancers is an important prognostic parameter for colorectal cancer patients. We examined whether the proliferative activities of tumor and stromal components play important roles in the increase of tumor thickness and the progression of colorectal cancers. Colorectal cancers were classified into thin and thick groups according to tumor thickness. The proliferative activities of fibroblasts and endothelial cells were immunohistochemically evaluated in 157 T3 ulcerative-type colorectal cancers by CD31/MIB-1 (anti-Ki-67 antigen) double staining. The MIB-1 labeling index was estimated as the percentage of fibroblasts with positive nuclei. The CD31-positive microvessels lined by MIB-1-positive endothelial cells were assessed. The proliferative microvessel index was defined as the percentage of proliferative microvessels relative to all microvessels. The fibroblast MIB-1 labeling index was the only parameter significantly associated with tumor thickness ( P=0.049). High fibroblast MIB-1 labeling indices showed significant correlation with tumor recurrence in the thin group ( P=0.020). High proliferative microvessel index was a significant parameter of tumor recurrence in the thick group ( P=0.003) in multivariate analyses. This study strongly suggests that proliferative activities of stromal components are useful parameters of tumor biology and of prognosis for T3 ulcerative-type colorectal cancer patients.