title: Diagnosis of serous tubal intraepithelial carcinoma based on morphologic and immunohistochemical features:  a reproducibility study.
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.
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. kvisvana@jhsph.edu
authors: Kala
authors: K
authors: Visvanathan
authors: Russell
authors: R
authors: Vang
authors: Patricia
authors: P
authors: Shaw
authors: Amy
authors: A
authors: Gross
authors: Robert
authors: R
authors: Soslow
authors: Vinita
authors: V
authors: Parkash
authors: Ie-Ming
authors: IeM
authors: Shih
authors: Robert J
authors: RJ
authors: Kurman
mesh_terms: D000465:Algorithms; D002278:Carcinoma in Situ / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D005185:Fallopian Tube Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D015588:Observer Variation; D010051:Ovarian Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000378:metabolism; D015203:Reproducibility of Results; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53