PIK3CA missense mutation is associated with unfavorable outcome in grade 3 endometrioid carcinoma but not in serous endometrial carcinoma

• PIK3CA exon 9/exon 20 mutations are found in 20% of high-grade endometrial carcinomas.
• There is no significant difference in mutations across histological types.
• Mutations are associated with unfavorable outcome in grade 3 endometrioid carcinomas.

ObjectiveTo evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas.MethodsWe assessed PIK3CA mutational status in exon 9 and exon 20 hot spots by Sanger sequencing of DNA derived from formalin fixed paraffin embedded tissue of 57 grade 3 endometrioid, 26 serous, 11 clear cell and 5 dedifferentiated carcinomas. We correlated PIK3CA mutation status with clinicopathological and other molecular parameters. Univariate and multivariate disease specific survival analysis was performed using Kaplan–Meier and Cox regression analyses.ResultsPIK3CA exon 9 or exon 20 missense mutations were identified in 20 of 99 (20%) high-grade endometrial carcinomas without significant difference across histological types (p = 0.22). Presence of PIK3CA exon 9 or exon 20 missense mutations was associated with shorter disease specific survival within grade 3 endometrioid (p = 0.0029) but not endometrial serous (p = 0.57) carcinoma based on univariate analysis. Within grade 3 endometrioid carcinoma, PIK3CA exon 9 or exon 20 missense mutations were more commonly observed in cases that were deficient for mismatch repair protein expression (p = 0.0058) and showed loss of ARID1A expression (p = 0.037).ConclusionsPIK3CA exon 9 or exon 20 missense mutations are present across all histological types of high-grade endometrial carcinomas but a significant outcome association is only seen in grade 3 endometrioid carcinoma, suggesting a greater biological importance in this tumor type.