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The Cancer Genome Atlas (TCGA) current molecular classification has established four categories with prognostic and predictive values in endometrial cancer (EC): POLE mutated, microsatellite instable (MSI), no specific molecular profile (NSMP), and p53 abnormal. In this context, NSMP represents the most heterogeneous subgroup, underlying several molecular alterations with unknown clinical value. The aim of this study is to evaluate how PIK3CA mutations could affect the prognosis of NSMP subgroup. Formalin-fixed paraffin-embedded (FFPE) tumour samples of 112 stage I EC patients treated at Careggi University Hospital, Florence (Italy) were gathered. p53 status by immunochemistry (IHC), microsatellite status by IHC and/or real time PCR, PIK3CA mutations by real time PCR, and POLE status by NGS sequencing were assessed. The primary endpoint was disease-free survival (DFS). Among 112 patients analyzed, 39 patients were p53 wild-type. Among them, a statistically significant difference in DFS between PIK3CA mutated and not mutated patients was found (p=0.029). 20 patients out of 39 (51%) were p53 wild-type/MSS. 9 of 20 (45%) p53 wild-type/MSS patients had POLE status known and they were all wild-type, however POLE status was not known for the remaining 11 patients. In the subgroup of 20 patients p53 wild-type/MSS, PIK3CA mutated patients showed a statistically significant worse DFS compared to PIK3CA wild-type (p=0.032). PIK3CA mutations negatively influence the outcomes of stage I EC patients with NSMP as the p53 wild-type/MSS. Therefore, PIK3CA testing might be implemented in clinical practice to further stratify the risk of EC patients without a specific molecular mark according to the current TCGA molecular classification, such as NSMP subgroup, in order to optimize adjuvant treatments.
Angelis et al. (Sat,) studied this question.