TP53 Alterations Are an Independent Adverse Prognostic Indicator in Pseudomyxoma Peritonei of Appendiceal Origin Following Cytoreductive Surgery and Intraperitoneal Chemotherapy.

Histologic grade is a key predictor for pseudomyxoma peritonei (PMP) of appendiceal origin that is used to guide clinical management. However, some tumors demonstrate disease behavior that deviates from their histologic grade. A recent study suggested that TP53, GNAS , and RAS mutation analysis could stratify tumors into distinct molecular groups with different prognosis. We investigated molecular alterations in 114 patients with PMP of appendiceal origin who were uniformly treated with cytoreductive surgery with intraperitoneal chemotherapy (CRS+IPCT). Tumors were separated into 4 groups based on their predominant genomic alteration: RAS -mut, GNAS -mut, TP53 -mut, and triple-negative ( RAS/GNAS/TP53 -wildtype). The results were correlated with World Health Organization (WHO) grade, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS) from the time of CRS+IPCT using multivariate Cox proportional hazard analysis. Fifty percent of TP53 -mut were WHO grade 3 compared with 38% triple-negative, 10% RAS -mut, and 7% GNAS -mut tumors ( P <0.001). The TP53 -mut group exhibited a significantly reduced OS compared with other groups ( P <0.001). No significant OS difference was identified between RAS -mut, GNAS -mut, and triple-negative groups ( P >0.05). In grade 3 PMP, TP53 -mut was significantly associated with reduced OS ( P =0.002). In the multivariate analysis for OS after CRS+IPCT, TP53 -mut [hazard ratio (HR) 3.23, P =0.004] and WHO grade (grade 2 HR 2.73, P =0.03 and grade 3 HR 5.67, P <0.001) were the only independent predictors of survival. Our results suggest that, in addition to tumor grade, TP53 status may help to provide a more patient-centered approach in guiding therapy in PMP.