title: Prognostic significance of p21 and p27 protein, apoptosis, clinical and histologic factors in rectal cancer without lymph node metastases.
abstract: 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).
authors.affiliation: Department of Surgery, Medical University of Lübeck, Germany. ao.schwandner@t-online.de
authors.forename: O
authors.initials: O
authors.lastname: Schwandner
authors.forename: H-P
authors.initials: HP
authors.lastname: Bruch
authors.forename: R
authors.initials: R
authors.lastname: Broll
mesh_terms: D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000032:analysis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis*; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D020287:In Situ Nick-End Labeling; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D012004:Rectal Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000032:analysis*
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27