The genomic heterogeneity of FIGO grade 3 endometrioid carcinoma impacts diagnostic accuracy and reproducibility Journal Article
| Authors: | Hussein, Y. R.; Broaddus, R.; Weigelt, B.; Levine, D. A.; Soslow, R. A. |
| Article Title: | The genomic heterogeneity of FIGO grade 3 endometrioid carcinoma impacts diagnostic accuracy and reproducibility |
| Abstract: | The Cancer Genome Atlas (TCGA) identified 4 groups of endometrial carcinomas based on an integrated genomic characterization: POLE ultramutated (POLE), microsatellite instability-high, copy number-low (CN-L), and copy number-high (CN-H). In that study, CN-H comprised all of the serous carcinoma cases and 25% of all International Federation of Gynecology and Obstetrics (FIGO) Grade 3 endometrioid carcinoma cases. In this study, 2 expert gynecologic pathologists undertook a morphologic reassessment of the FIGO Grade 3 endometrioid carcinoma subset of the TCGA study cohort, including an analysis for evidence of serous differentiation. Interobserver variability κvalues are reported for the histologic evaluation of all 4 genomic clusters, and diagnostic discrepancies are discussed. Overall, there were 55 agreements, 6 disagreements, and 14 deferrals. Of the 75 cases analyzed, 6 cases had a consensus morphologic diagnosis of serous carcinoma, but only 2 of these cases had a serous carcinoma genotype, whereas the remaining 4 cases were genotypically endometrioid carcinoma. For the CN-H group, 2 of 15 cases were serous carcinoma by morphology and genotype, whereas at least 1 pathologist interpreted the remaining 13 cases as endometrioid carcinoma. The interobserver agreement rate was highest in the CN-L group (90%; κ=0.9), compared with the other genomic groups (POLE: 62%, κ=0.55; microsatellite instability-high: 78%, κ=0.74; and CN-H: 53%, κ=0.48). Our review confirms that most high-grade endometrial carcinomas diagnosed by TCGA as FIGO Grade 3 endometrioid carcinoma are indeed endometrioid carcinomas by morphology and genotype, and that the reproducibility of histologic diagnosis between pathologists varies between the TCGA-integrated genomic clusters. © 2015 International Society of Gynecological Pathologists. |
| Keywords: | human tissue; unclassified drug; major clinical study; endometrial cancer; cancer diagnosis; endometrioid carcinoma; endometrium carcinoma; diagnostic accuracy; reproducibility; consensus; protein; genotype; protein p53; histology; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; genomics; pathologist; cancer morphology; genotype phenotype correlation; endometrioid; serous; tcga; interobserver agreement; human; female; priority journal; article; arid1a protein; international federation of gynecology and obstetrics grade 3 |
| Journal Title: | International Journal of Gynecological Pathology |
| Volume: | 35 |
| Issue: | 1 |
| ISSN: | 0277-1691 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2016-01-01 |
| Start Page: | 16 |
| End Page: | 24 |
| Language: | English |
| DOI: | 10.1097/pgp.0000000000000212 |
| PROVIDER: | scopus |
| PUBMED: | 26166718 |
| PMCID: | PMC4934379 |
| DOI/URL: | |
| Notes: | Appeared as a platform presentation at the 103rd United States and Canadian Academy of Pathology (USCAP) Annual Meeting, March 1-7, 2014, San Diego, CA -- Article -- Export Date: 3 February 2016 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work