John B McIntyre1, Gregg S Nelson2, Prafull Ghatage3, Don Morris1, Máire A Duggan4, Cheng-Han Lee5, Corinne M Doll1, Martin Köbel4. 1. Department of Oncology, University of Calgary, Calgary, Alberta, Canada; Translational Laboratory, Tom Baker Cancer Center, Calgary, Alberta, Canada. 2. University of Calgary, Calgary, Alberta, Canada; Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada. Electronic address: gsnelson@ucalgary.ca. 3. University of Calgary, Calgary, Alberta, Canada; Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada. 4. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; Calgary Laboratory Services, Calgary, Alberta, Canada. 5. Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, Alberta, Canada.
Abstract
OBJECTIVE: To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas. METHODS: We 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. RESULTS: PIK3CA 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). CONCLUSIONS: PIK3CA 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.
OBJECTIVE: To evaluate the outcome association of PIK3CA mutational status within histological types of rigorously classified high-grade endometrial carcinomas. METHODS: We 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. RESULTS:PIK3CA 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). CONCLUSIONS:PIK3CA 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.
Authors: Emeka K Enwere; Elizabeth N Kornaga; Michelle Dean; Theodora A Koulis; Tien Phan; Maria Kalantarian; Martin Köbel; Prafull Ghatage; Anthony M Magliocco; Susan P Lees-Miller; Corinne M Doll Journal: Mod Pathol Date: 2017-01-06 Impact factor: 7.842
Authors: Caroline C Billingsley; David E Cohn; David G Mutch; Erinn M Hade; Paul J Goodfellow Journal: Int J Gynecol Cancer Date: 2016-06 Impact factor: 3.437
Authors: Siv Mjos; Henrica M J Werner; Even Birkeland; Frederik Holst; Anna Berg; Mari K Halle; Ingvild L Tangen; Kanthida Kusonmano; Karen K Mauland; Anne M Oyan; Karl-Henning Kalland; Aurélia E Lewis; Gordon B Mills; Camilla Krakstad; Jone Trovik; Helga B Salvesen; Erling A Hoivik Journal: Sci Rep Date: 2017-08-31 Impact factor: 4.379