Abstract
BACKGROUND: Grade and histotype of ovarian carcinomas are often used as surrogates of molecular subtypes. We examined factors affecting pathologists' reproducibility in two prospective studies. METHODS: Two pathologists independently reviewed slides from 459 incident ovarian cancers in the Nurses' Health Study (NHS) and NHSII. We described agreement on tumor characteristics using percent agreement and Cohen's standard kappa (κ) coefficients. We used logistic regression, with disagreement as the outcome, to evaluate the contribution of case and tumor characteristics to agreement. RESULTS: Inter-rater agreement was 95% (κ = 0.81) for carcinoma versus borderline, 89% (κ = 0.58) for grade and 85% (κ = 0.71) for histotype. Inter-rater grading disagreement was higher for non-serous histotypes (OR = 4.66, 95% CI 2.09-10.36) and lower for cancers with bizarre atypia (OR = 0.13, 95% CI 0.04-0.38). Agreement with original pathology reports was 94% (κ = 0.73) for carcinoma versus borderline, 78% (κ = 0.60) for histotype, and 79% (κ = 0.24) for grade. Grading disagreement was significantly lower for tumors with 'solid, pseudoendometrioid or transitional' (SET) architecture (OR = 0.08, 95%CI 0.01-0.84). Date of original diagnosis, hospital type, number of slides available for review, tumor stage, and slide quality were not related to agreement. CONCLUSION: Overall, inter-rater agreement for tumor type and grade for archival tissue specimens was good. Agreement between the consensus review and original pathology reports was lower. Factors contributing to grading disagreement included non-serous histotype, absence of bizarre atypia, and absence of SET architecture.