Metallothioneins and p53 proteins expression as a prognostic marker for colon cancer patients

ARRIAGA, JUAN MARTÍN; BRAVO, ALICIA INÉS; BRUNO, LUISINA; BAYO MORALES SERGIO; SÁNCHEZ LORIA, FERNANDO; PAIROLA, ALEJANDRO; HUERTAS, EDUARDO; LEVY, ESTRELLA MARIEL; MORDOH, JOSÉ; BIANCHINI, MICHELE

Firenze

Congreso; XXXIX Meeting of the International Society of Oncology and Bio Markers (ISOBM Conference); 2011

Background: colorectal cancer (CRC) is staged according to the extent of primary organ involvement and metastatic spread to lymph nodes or distant organs. Unfortunately, the TNM-system alone does not allow precise prognosis for an individual patient; for this reason, studies to determine the prognostic value of novel molecular markers are awaited. Study Aim: our study aimed at the evaluation of MT and p53 expression in CRC and at correlating their combined intensity with selected clinical and pathological variables of the disease, in order to define their prognostic significance. Methods and Materials/Patients: CRC specimens, from 103 patients, were retrospectively analyzed by IHC for MT and p53 proteins expression, using two monoclonal antibodies, clones E9 and DO-7 respectively. For the outcome analysis, survival curves were generated according to the Kaplan-Meier method, and univariate survival distributions were compared with the use of the log-rank test. Hazard ratios for univariate and 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 Duke’s 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 < 0.06) and DFS ([HR] = 2.5; P < 0.07). 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’ stage B and C colorectal cancer.