High Grade Endometrial Carcinoma: Serous & Grade 3 Endometrioid Carcinoma Have Different Immunophenotypes and Outcomes
A Alkushi, M Kobel, SE Kalloger, CB Gilks. King Fahad National Guard Hospital, Riyadh, Saudi Arabia; University of British Columbia, Vancouver, BC, Canada
Background: High-grade endometrial carcinomas are a heterogeneous group of tumors and include grade 3 endometrioid, serous, and clear cell carcinomas. There are conflicting data about the prognosis of these endometrial carcinoma subtypes; this might be due to lack of reproducibility in classifying some tumors based on their cell type. The purpose of this study was to examine differences in immunophenotype and prognosis in a series of high grade endometrial carcinomas.
Design: We selected 180 endometrial carcinomas of pure serous, endometrioid or clear cell type. We chose the following immunohistochemical markers (ER, IMP3, p16, p53, PR, PTEN) as being significantly differentially expressed in pure endometrial carcinomas subtypes and validated their discriminatory value on this set of tumors. Tumors were stratified into four groups based on their cell type and grade: endometrioid tumors of grade 1 or 2, endometrioid tumors of grade 3, serous, and clear cell carcinomas.
Results: Univariate survival analysis revealed significant differences in outcome between the four groups (p<0.0001), with significantly longer disease specific survival for grade 1 or 2 versus grade 3 endometrioid carcinoma (p=0.0001), and grade 3 endometrioid versus serous carcinoma (p=0.0003). p16, PTEN and IMP3 expression was observed more frequently in serous carcinomas, compared to grade 3 endometrioid carcinomas (p<0.0001, p=0.021 and p=0.031, respectively). These three markers showed the highest sensitivity and specificity expressed as area under the curve with 0.85, 0.69 and 0.71, respectively. ER and p53 approached but did not reach significance for differential expression in grade 3 endometrioid versus serous carcinomas (p=0.055 and p=0.068, respectively). A combination of p16 and PTEN predicts grade 3 endometrioid versus serous type with a sensitivity of 90.0% and specificity of 96.8%.
Conclusions: p16 and PTEN can aid in the diagnosis of grade 3 endometrioid versus serous carcinoma of the endometrium, and are superior to ER and p53 for this purpose. Grade 3 endometrioid carcinomas have a significantly better prognosis than serous carcinomas of the endometrium.
Tuesday, March 10, 2009 9:15 AM
Platform Session: Section D, Tuesday Morning