Restricted overexpression of p53 immunohistochemistry (p53IHC RO) as prognostic after colorectal cancer (CRC) resection

Van den Eynde, Marc [UCL] Le, Ha Molinh Nyiraneza, Christine Kartheuser, Alex [UCL] Detry, Roger [UCL] Humblet, Yves [UCL] Léonard, Daniel [UCL] Remue, Christophe [UCL] Dahan, Karin [UCL] van Maanen, Aline [UCL] Mourin, Anne [UCL] Sempoux, Christine [UCL]

Background: p53IHC RO was previously described as a distinct pattern from the negative or diffuse p53 IHC expression. p53IHC RO is characterized by a limited number of homogenously scattered strongly positive CRC cells and is associated with some clinico-pathologic CRC feature. The prognostic impact of p53IHC RO remains unknown. Methods: p53 and MMR (MLH1, MSH2, MSH6 and PMS2) proteins IHC expression were performed on CRC primary tumors from an unselected cohort of patients who underwent surgery at the Cliniques St-Luc between 1995 and 2000. p53 IHC results were defined as negative, diffuse or restricted expression. Clinico-pathologic CRC characteristics and patients follow-up were available for this analysis. Comparisons of numerical and categorical clinico-pathological data were evaluated respectively by ANOVA and Fisher exact tests between p53 expression groups. Progression-Free Survival (PFS) and Overall Survival (OS) analyses were performed using Kaplan-Meier method and compared with the log-rank test (Bonferroni correction applied for multiplicity). Uni and multivariate PFS and OS regression were performed using a Cox Proportional Hazard model. Results: Among 100 CRCs (99 patients), p53 IHC expression was categorized as restricted (n=36), diffuse (n= 46) or negative (n=18). p53IHC RO (total n=36, defective MMR n=20, proficient MMR n=16) was associated with age (≥60y), proximal location, poor differentiated CRC, and a lowest lymph node ratio (LNR) (p<0.05). Among the analysed defective MMR CRCs, 20/24 was p53IHC RO (p<0.001). After a mean follow-up of 13 years after CRC resection, median PFS and OS were significantly higher in the p53IHC RO group as compared with the diffuse and negative p53 IHC expression (median PFS respectively not reached vs 40.9 vs 22.8 months, p<0.001 and median OS respectively not reached vs 70.7 vs 48.0 months, p=0.009). LNR, synchronous metastases and p53IHC RO were significantly associated with a better PFS in multivariate analysis (p<0.05). Conclusions: p53IHC RO is a prognostic factor after CRC resection. These results must be confirmed on a larger cohort but could be clinically relevant for prognosis.