Molecular prognostic factors in rectal cancer treated by preoperative chemoradiotherapy

The present study evaluated the expression of p53, pRb, hMLH1 and MDM2 prior to preoperative chemoradiotherapy (CRT) in patients with rectal cancer, and attempted to determine any correlation with treatment outcome Forty-five patients with available pretreatment biopsy tissues and who received preoperative CRT were enrolled in this study Preoperative CRT consisted of a median 504 Gy and 2 cycles of concurrent administration of 5-fluorouracil + leucovorin Surgery was performed approximately seven weeks after CRT Protein expression in formalin-fixed paraffin-embedded biopsy specimens was assessed by immunohistochemistry A positive expression of p53, pRb, hMLH1 and MDM2 was found in 40, 467, 40 and 667% of the tissue specimens, respectively The 5-year overall (OS), disease-free (DFS) and locoregional recurrence-free survival (LRFS) rates for patients included in the study were 71 3,66 1 and 609%, respectively p53 expression presented a significantly different OS (positive vs negative, 45 8 vs 862%, p=0 02) However, the expression of pRb, hMLH1 and MDM2 was not significant for OS The expression of p53 was a borderline significant prognostic factor for DFS and for LRFS Age, p53 and MDM2 expression were significant factors in the multivariate analysis performed for OS with 12 covariates, including 8 clinicopathological parameters and 4 proteins No significant factor affected DFS or LRFS in the multivariate analysis We suggest that the expression of p53 is a potential marker of survival Determinations of this protein expression may be useful for selecting candidates from rectal cancer patients for more tailored treatment