Combined metallothioneins and p53 proteins expression as a prognostic marker in patients with Dukes? stage B and C colorectal cancer

J.M. ARRIAGA; I.A. BRAVO; L. BRUNO; S. MORALES BAYO; A. HANNOIS; S. BAFFA TRASCI; E.M. LEVY; J. MORDOH; M. BIANCHINI

HUMAN PATHOLOGY

W B SAUNDERS CO-ELSEVIER INC

Año: 2012 vol. 43 p. 1695 - 1703

0046-8177

Purpose: our study aimed to evaluate MT and p53 expression in CRC and to correlate their combined expression with selected clinical and pathological variables of the disease, in order to define their prognostic significance. Methods: CRC specimens from 99 patients were retrospectively analyzed by IHC for MT and p53 expression. Survival curves were generated according to the Kaplan-Meier method, and univariate survival distributions were compared with the use of the log-rank test. Multivariate models were computed using Cox proportional-hazards regression. This research was approved by the institutional review boards of all centers. Results: tumors showing concomitant high MT expression and negative p53 (MTH/p53-) were significantly inversely related to depth of invasion, frequency of nodal metastasis and Dukes? stage (P < 0.01). In univariate analysis, patients with MTH/p53- phenotype showed a better OS ([HR] = 3.29; P < 0.05) and DFS ([HR] = 2.37; P < 0.05). In multivariate analysis, considering staging, MT, and MT+p53 variables, in 83 Dukes? stage B and C patients, MTH/p53- combination was the sole factor showing an independent prognostic value for OS ([HR] = 3.88; P < 0.1) and DFS ([HR] = 2.56; P < 0.1). Conclusions: the combined analysis of MT and p53 may enhance the prognostic power of each individual marker by predicting the progression of the disease and contributing to a better identification of patients at low risk for mortality, especially for those with Dukes? stages B and C colorectal cancer.