Salwa Bakhsh1, Mary Kinloch1, Lien N Hoang1, Robert A Soslow2, Martin Köbel3, Cheng-Han Lee4, Jessica N McAlpine5, Melissa K McConechy6, C Blake Gilks1. 1. Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 2. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 3. Department of Pathology and Laboratory Medicine, University of Calgary and Calgary Laboratory Services, Calgary, Alberta, Canada. 4. Department of Laboratory Medicine and Pathology, Royal Alexandra Hospital and University of Alberta, Edmonton, Alberta, Canada. 5. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada. 6. Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Abstract
AIMS: To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations. METHODS AND RESULTS: Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype. CONCLUSIONS: POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy.
AIMS: To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations. METHODS AND RESULTS: Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype. CONCLUSIONS: POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy.
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