title: Evidence for a dualistic model of high-grade serous carcinoma: BRCA mutation status, histology, and tubal intraepithelial carcinoma.
abstract: Most early adnexal carcinomas detected in asymptomatic women with germline BRCA mutations (BRCA) present as serous tubal intraepithelial carcinomas (STIC). However, STICs are found in only ∼40% of symptomatic high-grade serous carcinomas (HGSCs) and less frequently in pseudoendometrioid variants of HGSC. Consecutive cases of untreated HGSC from BRCA and BRCA women with detailed fallopian tube examination (SEE-FIM protocol) were compared. STIC status (+/-) was determined, and tumors were classified morphologically as SET ("SET", >50% solid, pseudoendometrioid, or transitional) or classic predominate ("Classic"). SET tumors trended toward a higher frequency in BRCA versus BRCA women (50% vs. 28%, P=0.11), had a significantly younger mean age than those with classic HGSC in BRCA women (mean 56.2 vs. 64.8 y, P=0.04), and displayed a better clinical outcome in both groups combined (P=0.024). STIC was significantly more frequent in tumors from the BRCA cohort (66% vs. 31%, P=0.017) and specifically the BRCA tumors with classic morphology (83%) versus those with SET morphology (22%, P=0.003). Overall, several covariables-histology, BRCA status, age, coexisting STIC, and response to therapy-define 2 categories of HGSC with differences in precursor (STIC) frequency, morphology, and outcome. We introduce a dualistic HGSC model that could shed light on the differences in frequency of STIC between symptomatic and asymptomatic women with HGSC. This model emphasizes the need for further study of HGSC precursors to determine their relevance to the prevention of this lethal malignancy.
authors.affiliation: *Department of Pathology, Division of Women's and Perinatal Pathology §Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Brigham and Women's Hospital ‡Dana Farber Cancer Institute, Boston MA †Department of Pathology, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Howitt
authors.forename: Suchanan
authors.initials: S
authors.lastname: Hanamornroongruang
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Lin
authors.forename: James E
authors.initials: JE
authors.lastname: Conner
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schulte
authors.forename: Neil
authors.initials: N
authors.lastname: Horowitz
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Crum
authors.forename: Emily E
authors.initials: EE
authors.lastname: Meserve
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001900:Boston; D002278:Carcinoma in Situ / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D004252:DNA Mutational Analysis; D005185:Fallopian Tube Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D008954:Models, Biological; D009154:Mutation; D060787:Neoplasm Grading; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010641:Phenotype; D011237:Predictive Value of Tests; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor