PTEN pathogenic variants are associated with poor prognosis in patients with advanced soft tissue sarcoma.

Background: We aimed to examine whether PTEN pathogenic variants (mutPTEN) were associated with overall survival (OS) in patients with advanced soft tissue sarcoma (STS) with the presence of one or more of the most common genomic alterations including p53, CDKN2A, RB1, and ATRX pathogenic variants.

Methods: This study included patients from Kaiser Permanente Northern California and Stanford Cancer Center with grade 2 or higher locally advanced and metastatic STS.

Results: A total of 174 patients had leiomyosarcoma (LMS), 136 had undifferentiated pleomorphic sarcoma (UPS), 78 had Liposarcoma (LPS), and 214 had other histology subtypes (Others). Among all patients with STS, OS was worse for those with mutPTEN versus wild-type PTEN (wtPTEN, adjusted HR [aHR] = 1.58 [95% CI, 1.11-2.23]), mutCDKN2A vs wtCDKN2A (aHR = 1.33 [95% CI .99-1.80]), and mutRB1 vs wtRB1 (aHR = 1.26 [95% CI 0.93-1.70[), while OS was similar for mutp53 vs wtp53 and mutATRX vs wtATRX. MutPTEN versus wtPTEN was consistently associated with worse OS in histologic subtypes including LMS and UPS and molecular subgroups.

Conclusion: MutPTEN vs wtPTEN was associated with worse OS in advanced STS. If confirmed, our findings could be helpful for prognostic stratification in clinical practice and for further understanding the molecular mechanisms of STS.