Prognostic significance of p21 and p27 protein, apoptosis, clinical and histologic factors in rectal cancer without lymph node metastases.

The aim of this study was to evaluate the prognostic role of clinical and histopathologic factors, cell-cycle regulator proteins (p21(Waf1/Cip1), p27(Kip1)), and apoptotic index in lymph node-negative rectal cancer. Formalin-fixed, paraffin-embedded tissue samples of 97 rectal carcinomas (UICC stages I and II) resected curatively within five years were used. Immunohistochemical analysis of protein expression was performed by monoclonal antibodies: p21 (clone SX118), p27 (clone SX53G8). Apoptosis was assessed by the TUNEL method. Clinical, surgical, histopathologic, and follow-up data were prospectively recorded in a computerized registry. To assess prognostic significance (end points: metachronous distant metastases, 5-year disease-free and overall survival), statistics included univariate and multivariate analysis (p < 0.05 statistically significant). Of the 97 rectal carcinomas without lymph node metastases, 46.4% (45/97) were p21-positive, 49.5% were p27-positive (48/97), whereas 27.8% (27/97) showed a high apoptotic index. Within a median follow-up of 54 months, 4 patients developed local recurrence (4.1%). Distant metastases occurred in 12 patients (12.4%). Univariate analysis showed that gender, UICC stage, p21 and p27 were significantly associated with the incidence of distant metastases (p < 0.05). UICC stage and p21 were the only factors to be significantly related to 5-year disease-free survival by univariate analysis (p < 0.05). Only UICC stage was significantly related to 5-year overall survival (p < 0.05). The apoptotic index was correlated neither to recurrence nor to survival (p > 0.05). Multivariate analysis demonstrated that gender, UICC stage and p21 were independently related to the incidence of distant metastases; however, UICC stage was the only independent factor predictive of 5-year disease-free survival and overall survival (p < 0.05).