Clinical Impact Of Histologic Subtypes And Somatic Mutations In Peritoneal Carcinomatosis From Colorectal Cancer.

e14621 Background: Peritoneal carcinomatosis (PC) occurs in 10 to 15% of colorectal carcinoma (CRC). Strategies combining surgical resection and hyperthermic intraperitoneal chemotherapy have improved PC outcome. The morphologic, phenotypic and molecular spectrum of CRC PC and their clinical impact are still unknown. Methods: We selected 70 CRC PC cases operated in our institute (34 men, 36 women, median age: 61, median follow-up: 3.9 years.). The following investigations were performed: pathologic review; immunohistochemistry, focused on microsatellite instability (MSI) and CRC markers; mutational status of KRAS, BRAF and TP53. Results: 51 % of PC cases were pure or mixed mucinous carcinoma. Histologic types of PC and primary CRCwere concordant in 80% of cases. Lymphovascular and perineural infiltrations were only observed in 20 and 23% of cases, probably reflecting the preferential spread of PC by surface graft. 90% of cases displayed usual CRC phenotype: CK20+/CK7-/villine+/CDX2+. 96% of PC cases were microsatellite stable (MSS) and 58, 46 and 6% showed TP53, KRAS and BRAF mutations, respectively. No significant association was observed between the histologic type and sex, location, peritoneal index or molecular profile. Mucinous PC had a better relapse free survival (RFS) than conventional lieberkuhnian PC (P=0.04). KRAS/BRAF wild type PC had a better overall survival (OS) than KRAS or BRAF mutated PC, the latter group having the worst outcome (P<0.001). Conclusions: The high rate of mucinous PC suggested a propensity for peritoneal location in primary mucinous CRC. The high rate of MSS tumors, TP53 and KRAS mutations revealed that a large part of PC could be part of the chromosomic instability molecular group. Poor RFS with lieberkuhnian PC raises the question of greater aggressiveness for this histologic type. Consistent with previous reports in metastatic CRC, poor OS was associated with KRAS and particularly BRAF mutations. These preliminary and original results may indicate a peritoneal tropism and a particular behavior for mucinous CRC and need to be prospectively confirmed to determine whether mucinous CRC and PC could benefit from particular therapeutic approaches.