Histotype-Genotype Correlation in 36 High-Grade Endometrial Carcinomas
Lien N Hoang, Melissa K McConechy, Martin Koebel, Guangming Han, Marjan Rouzbahman, Ben Davidson, Julie Irving, Rola Ali, Sam Leung, Esther Oliva, Marisa R Nucci, Rob A Soslow, David G Huntsman, C Blake Gilks, Cheng-Han Lee. University of British Columbia, Vancouver, Canada; University of Calgary, Calgary, Canada; University of Toronto, Toronto, Canada; Norwegian Radium Hospital, Oslo, Norway; Massachusetts General Hospital, Boston, MA; Brigham and Women's Hospital, Boston, MA; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Serous carcinomas and endometrioid/clear cell carcinomas of the endometrium are genetically distinct tumor types with differing prognoses. The distinction between these tumor types can be difficult, particularly in high-grade cases.
Design: 36 high-grade endometrial carcinomas (J Path 2012;228:20-30) were included; 23 endometrioid/clear cell genotype (PTEN and ARID1A mutation either one without TP53 and PPP2R1A mutation) and 13 serous genotype (TP53 and/or PPP2R1A mutation without ARID1A or PTEN mutation). 8 pathologists reviewed representative online slides and rendered diagnoses before and after receiving p53, p16 and ER immunoprofiles. Kappa statistics for histotype-genotype concordance were calculated for each pathologist.
Results: The average kappa values for histotype-genotype concordance was 0.56 (range: 0.31-0.67) based on morphology alone, and improved to 0.68 (range: 0.54-0.81) after immunoprofile consideration (p=0.009). Genotype incompatible diagnoses were rendered by at least 2 pathologists in 12 of 36 cases (33%) (3 with 2/8, 2 with 3/8, 2 with 4/8, 1 with 5/8, 3 with 6/8 and 1 with 8/8). Scenarios prone to genotype-incompatible diagnoses are shown in Table 1.
|Endometrioid/clear cell genotype that mimic serous||Solid growth with high nuclear grade and high MI||p53 not helpful; Focal endometrioid glandular pattern (at periphery), extensive comedonecrosis and squamoid areas suggest endometrioid|
|Papillary pattern with cell budding and intermediate nuclear grade||Low MI favors endometrioid and/or clear cell; p53 recommended: normal result suggests endometrioid and/or clear cell carcinoma|
|Serous genotype that mimic endometrioid/clear cell||Papillary pattern with uniform nuclei||Diffusely elevated MI favors serous; p53 recommended: abnormal result (either diffuse or completely absent) suggests serous|
|Papillary pattern with endometrioid-like glandular pattern||Diffuse high nuclear grade or diffusely elevated MI favors serous; p53 recommended: abnormal result suggests serous|