Evidence for a Dualistic Model of High-grade Serous Carcinoma. (March 2015)

• Record Type: Journal Article
• Authors: Howitt, Brooke E.; Hanamornroongruang, Suchanan; Lin, Douglas I.; Conner, James E.; Schulte, Stephanie; Horowitz, Neil; Crum, Christopher P.; Meserve, Emily E.
• Is Part Of: American journal of surgical pathology. Volume 39:Number 3(2015)
• Publication Date: 2015-03
• Subjects: Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000369
• Languages: English
• ISSNs: 0147-5185

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>Most early adnexal carcinomas detected in asymptomatic women with germline <italic>BRCA</italic> mutations (<italic>BRCA</italic><sup>+</sup>) 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 <italic>BRCA</italic><sup>+</sup> and <italic>BRCA</italic><sup>−</sup> 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 <italic>BRCA</italic><sup>+</sup> versus <italic>BRCA</italic><sup>−</sup> women (50% vs. 28%, <italic>P</italic>=0.11), had a significantly younger mean age than those with classic HGSC in <italic>BRCA</italic><sup>−</sup> women (mean 56.2 vs. 64.8 y, <italic>P</italic>=0.04), and displayed a better clinical outcome in both groups combined (<italic>P</italic>=0.024). STIC was significantly more frequent in tumors from the <italic>BRCA</italic><sup>−</sup> cohort (66% vs. 31%, <italic>P</italic>=0.017) and specifically the <italic>BRCA</italic><sup>−</sup> tumors with classic morphology (83%) versus those with SET morphology (22%, <italic>P</italic>=0.003). Overall, several covariables—histology, <italic>BRCA</italic> 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.</p> </sec> </abstract>