Original ArticlesDiagnosis of Serous Tubal Intraepithelial Carcinoma Based on Morphologic and Immunohistochemical Features A Reproducibility StudyVisvanathan, Kala MBBS, FRACP, MHS*,†; Vang, Russell MD‡,§; Shaw, Patricia MD¶; Gross, Amy MS*; Soslow, Robert MD∥; Parkash, Vinita MD; Shih, Ie-Ming MD, PhD†,‡,§; Kurman, Robert J. MD†,‡,§Author Information *Department of Epidemiology Johns Hopkins Bloomberg School of Public Health †Departments of Oncology ‡Pathology §Gynecology and Obstetrics Johns Hopkins School of Medicine, Baltimore, MD ∥Department of Pathology, Memorial Sloan-Kettering Cancer Center ¶Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto Conflicts of Interest and Source of Funding: This article was supported by CDMRP grant OC100517 from the Department of Defense. K.V. was also supported by a KO7 Preventive Oncology Award (KO7Ca111948). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Kala Visvanathan, MBBS, MD, FRACP, MHS, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (e-mail: [email protected]). The American Journal of Surgical Pathology: December 2011 - Volume 35 - Issue 12 - p 1766-1775 doi: 10.1097/PAS.0b013e31822f58bc Buy Metrics Abstract There is compelling evidence that serous tubal intraepithelial carcinoma (STIC) is a precursor of high-grade serous ovarian carcinoma. Large-scale studies are now required to determine its biological significance and clinical implication. Before conducting these studies, a reproducible classification for STIC is needed, and that is the goal of this study. This study involved 6 gynecologic pathologists from 4 academic institutions and 3 independent rounds of review. In round 1, sixty-seven lesions ranging from normal, atypical, to STICs were classified by 5 pathologists on the basis of predetermined morphologic criteria. Interobserver agreement for the diagnosis of STIC versus not STIC was fair [κ=0.39; 95% confidence interval (CI) 0.26, 0.52], and intraobserver reproducibility ranged from fair to moderate on the basis of percentage agreement and κ. Round 2 involved testing revised criteria that incorporated morphology and immunohistochemistry (IHC) for p53 protein expression and Ki-67 labeling in 10 sets by 3 of the pathologists. The result was an improvement in interobserver agreement for the classification of STIC (κ=0.62; 95% CI 0.18, 1.00). An algorithm was then created combining morphology and IHC for p53 and Ki-67, and reproducibility was assessed as part of round 3. In 37 lesions reviewed by 6 pathologists, substantial agreement for STIC versus no STIC was observed (κ=0.73; 95% CI 0.58, 0.86). In conclusion, we have developed reproducible criteria for the diagnosis of STIC that incorporate morphologic and IHC markers for p53 and Ki-67. The algorithm we propose is expected to help standardize the classification of STIC for future studies. © 2011 Lippincott Williams & Wilkins, Inc.