title: Loss of SerpinA5 protein expression is associated with advanced-stage serous ovarian tumors.
abstract: Epithelial ovarian cancer, the most lethal neoplasm of the female genital tract, is usually diagnosed at an advanced stage as obvious symptoms are absent at early stages. This disease is believed to originate from malignant transformation of the ovarian surface epithelium or fallopian tube. Histologically, several subtypes are being recognized, with serous histology accounting for the majority of cases. Serous tumors include serous borderline tumors and serous carcinomas. A better understanding of the tumor biology and molecular mechanisms involved in these tumors is needed, as both patient management and prognosis differ substantially. Previous microarray analysis identified SerpinA5, a uPA inhibitor, as key regulator for indolent borderline behavior. As carcinomas are characterized by loss of SerpinA5 mRNA expression, we hypothesized that SerpinA5 protein expression is reduced or lost in carcinomas when compared with borderline tumors. We performed SerpinA5 immunohistochemical staining on 32 serous borderline tumors, 187 primary serous carcinomas and 62 serous omental metastases. Reduced or absent SerpinA5 protein staining was observed in carcinomas when compared with borderline tumors (P<0.001). SerpinA5 protein expression was significantly lowered in the omental metastases (P<0.001) when compared with the matching primary carcinoma. Interestingly, SerpinA5 protein expression was reduced in advanced-stage borderline tumors, often characterized by micropapillary growth and/or microinvasion, when compared with early-stage borderline tumors (P=0.015). In conclusion, SerpinA5 expression is significantly reduced in advanced-stage serous borderline tumors and serous carcinomas when compared with the early-stage counterparts, and reduction of expression is linked to more aggressive features of borderline tumors.
authors.affiliation: Department of Pathology, GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Ingrid T G W
authors.initials: IT
authors.lastname: Bijsmans
authors.forename: Kim M
authors.initials: KM
authors.lastname: Smits
authors.forename: Pauline
authors.initials: P
authors.lastname: de Graeff
authors.forename: G Bea A
authors.initials: GB
authors.lastname: Wisman
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
authors.forename: Brigitte F
authors.initials: BF
authors.lastname: Slangen
authors.forename: Adriaan P
authors.initials: AP
authors.lastname: de Bruïne
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
authors.forename: Nathalie L
authors.initials: NL
authors.lastname: Sieben
authors.forename: Koen K
authors.initials: KK
authors.lastname: Van de Vijver
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism / Q000556:secondary*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009852:Omentum / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000378:metabolism / Q000556:secondary*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D018046:Protein C Inhibitor / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018046:Protein C Inhibitor; C534934:SERPINA5 protein, human