title: Prognostic impact of HER3 based on protein and mRNA expression in high-grade serous ovarian carcinoma.
abstract: HER3 is a member of the epidermal growth factor family and was predominantly described as a negative prognostic factor in various solid tumors as well as in ovarian cancer. In this study, we investigated HER3 on protein and mRNA expression in histologically defined subtypes of ovarian cancer looking for an influence on patient's survival. Altogether, we examined HER3 in ovarian high-grade serous (HGSC, n = 320), low-grade serous (LGSC, n = 55), endometrioid (EC, n = 33), and clear cell (CCC, n = 48) carcinomas using immunohistochemistry (IHC) and quantitative real-time reverse transcription PCR (qRT-PCR). Univariate and multivariate analyses were performed to explore the association between HER3 and overall survival (OS) as well as progression-free survival (PFS). In HGSC, high HER3 mRNA expression was a favorable prognostic factor for PFS (P = 0.008) and OS (P = 0.052), while for high HER3 protein expression, a trend towards better survival was seen (OS P = 0.064; PFS P = 0.099). A subgroup of HGSC with negative HER3 staining and negative HER3 mRNA levels showed most unfavorable OS and PFS (P = 0.002 and P = 0.004, respectively). Using the multivariate Cox regression model, HER3 was predictive for prolonged PFS (HR, 0.48; 95% CI, 0.26-0.88; P = 0.018). All in all, we cannot confirm the reported negative prognostic impact of HER3 expression in high-grade serous ovarian carcinoma and moreover find a rather positive prognostic implication of HER3 in this major ovarian cancer histological subtype.
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany. ulrike.unger@charite.de.
authors.forename: Ulrike
authors.identifier: http://orcid.org/0000-0002-7238-4723
authors.initials: U
authors.lastname: Unger
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.affiliation: Department of Gynecology, Charité Universitätsmedizin Berlin, Berlin, Germany.|Tumorbank Ovarian Cancer Network (TOC), Department of Gynecology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ioana
authors.initials: I
authors.lastname: Braicu
authors.affiliation: Department of Gynecology, Charité Universitätsmedizin Berlin, Berlin, Germany.|Tumorbank Ovarian Cancer Network (TOC), Department of Gynecology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.affiliation: German Breast Group (GBG), Neu-Isenburg, Germany.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Loibl
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany.|Tumorbank Ovarian Cancer Network (TOC), Department of Gynecology, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
chemical_list: D012333:RNA, Messenger; C581292:ERBB3 protein, human; D020893:Receptor, ErbB-3
keywords: HER3; High-grade serous carcinoma; Ovarian; Prognosis