TP53 K351N mutation-associated platinum resistance after neoadjuvant chemotherapy in patients with advanced ovarian cancer.

ABSTRACT

OBJECTIVE: TP53 K351N mutation is associated with acquired cisplatin resistance in ovarian cancer cells following exposure to cisplatin. We investigated the effect of TP53 K351N mutation on outcome in patients with epithelial ovarian cancer (EOC) who received platinum-based chemotherapy. METHODS: We assessed TP53 K351N mutations by allele specific real-time PCR (AS-PCR) and DNA sequencing in tumor samples of 153 patients with stage IIIC/IV EOC. Clinicopathologic and follow-up data were collected by a retrospective chart review. RESULTS: TP53 K351N mutations were detected in 8 (11.27%) of 71 patients who underwent neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) but not in 82 patients who underwent primary debulking surgery (PDS) (P<0.01). In patients with relapse within 6 months, the relapse rate was 14 (19.72%) of 71 patients for NACT-IDS compared to 15 (18.29%) of 82 patients for PDS (P=0.49), and TP53 K351N mutation was observed in 8 of NACT-IDS 14 patients (57.14% P<0.01). In the patients retreated at first recurrence within 6 months, 7 with TP53 K351N mutation of 14 NACT-IDS patients exhibited progression of disease, compared to 2 of PDS 15 patients (50.00% vs. 13.33%, P=0.04). The median disease-free survival (DFS) for NACT-IDS was 13.0 months compared to 15.0 months for PDS (P=0.02). In multivariate analysis, TP53 K351N mutation is an independent factor for shorter DFS in the patients who underwent NACT-IDS (HR=19.05; P=0.01). CONCLUSIONS: TP53 K351N mutation may be associated with induction of platinum resistance after NACT in advanced EOC.