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[1139] Inter-Observer Agreement in Endometrial Carcinoma (EC) Diagnosis Varies Depending on TCGA Subgroup Assignment

Lien Hoang, Mary A Kinloch, Katherine Grondin, Cheng-Han Lee, Carol Ewanowich, Martin Kobel, David G Huntsman, Jessica N McAlpine, Robert Soslow, Blake Gilks.

Memorial Sloan Kettering Cancer Center, New York, NY; Saskatoon City Hospital, Saskatoon, SK, Canada; Laval University, Quebec City, QC, Canada; University of Edmonton, Edmonton, AB, Canada; University of Calgary, Calgary, AB, Canada; BC Cancer Agency, Vancouver, BC, Canada; Vancouver General Hospital, Vancouver, BC, Canada.

Background: We performed molecular analysis on a series of endometrial carcinomas and stratified them into the same molecular groups as modeled by the Cancer Genome Atlas (TCGA) (Br J Cancer 2015;113:299-310). Using this series, we examined interobserver histologic agreement within each of the 4 molecularly defined groups. The goal was to determine which group is most challenging to diagnose using standard histologic assessment.

Design: Seven gynecologic subspecialty pathologists based in different tertiary care centers assigned histologically-based diagnosis given 151 endometrial carcinomas using 1-2 representative slides from hysterectomy specimens. Inter-observer agreement in histotype diagnosis was then compared between each of the 4 TCGA groups.

Results: Inter-observer agreement in each of the 4 TCGA groups is summarized in Table 1. Consensus agreement in histotype diagnosis was excellent in the CN-L group, intermediate in the MSI and POLE, and lowest in the CN-H group.

Table 1. Inter-observer agreement of histologic diagnosis in the 4 molecularly classified TCGA groups.


 POLE MSI  CN-L  CN-H
 N 34  40  41  36
 Consensus
 Diagnosis *
22 (65%)  23 (58%) 37 (90%) 14 (39%)
 Histotype
 Distribution†
EC1-2: 19
EC3: 12
SC: 1
CCC: 0
DDEC: 1
Other: 1
EC1-2: 29
EC3: 7
SC: 0
CCC: 0
DDEC: 2
Other: 2
EC1-2: 37
EC3: 3
SC: 0
CCC: 0
DDEC: 0
Other: 1
EC1-2: 4
EC3: 4
SC: 23
CCC: 1
DDEC: 1
Other: 3




* All 7 pathologists in agreement
† Kappa values are calculated based on 5 major diagnostic categories: endometrioid, serous, clear cell, mucinous and other

Conclusions: The degree of diagnostic agreement made by gynecologic subspecialty pathologists varies depending on TCGA subgroup assignment. In the groups where inter-observer variability is less optimal (MSI, POLE, CN-H), there may be a role for ancillary immunohistochemical or molecular studies.