Prognostic factors of 87 ovarian yolk sac tumor (OYST) patients and molecular characteristics of persistent and recurrent OYST.

Objective: We aimed to explore the characteristics of OYST, particularly for persistent and recurrent OYST, in order to explore potential treatment options and thereby improve patient outcomes.

Methods: We retrospectively reviewed the clinical records of all patients with OYST at Fudan university Shanghai Cancer Center from December 3, 2005 to November 27, 2020. Furthermore, and performed whole-exome sequencing on 17 paired OYST (including 8 paired persistent and recurrent OYST) tumor and blood samples to elucidate the aberrant molecular features.

Results: Totally, 87 OYST patients were included between 2007/03/13 and 2020/11/17. With a median follow-up of 73 [3-189] months, 22 patients relapsed or disease persisted. Overall, 17 patients died with a median overall survival of 21 [3-54] months. Univariate and multivariate analysis revealed tumor histology and residual lesions were independently associated with event free survival and overall survival, cycles to AFP normalization were another independent risk factor for overall survival. For the 8 persistent and recurrent OYST: cancer driver genes including ANKRD36, ANKRD62, DNAH8, MUC5B, NUP205, RYR2, STARD9, MUC16, TTN, ARID1A and PIK3CA were frequently mutated; cell cycle, ABC transporters, HR, NHEJ and AMPK signal pathway demonstrated as the most significantly enriched pathways; TMB, DNA MMR gene mutation and MSI were significantly higher. Mutation signature 11, 19 and 30 were the dominant contributors in persistent and recurrent OYST mutation.

Conclusion: Persistent and recurrent OYST associated with poor prognosis, and probably susceptible to immune checkpoint blockade therapy. Molecular characteristics contributed to predict the persistence and recurrence of OYST.