title: Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients.
abstract: Several members of the human kallikrein-related peptidase family, including KLK6, are up-regulated in ovarian cancer. High KLK6 mRNA or protein expression, measured by quantitative polymerase chain reaction and enzyme-linked immunoassay, respectively, was previously found to be associated with a shortened overall and progression-free survival (OS and PFS, respectively). In the present study, we aimed at analyzing KLK6 protein expression in ovarian cancer tissue by immunohistochemistry. Using a newly developed monospecific polyclonal antibody, KLK6 immunoexpression was initially evaluated in normal tissues. We observed strong staining in the brain and moderate staining in the kidney, liver, and ovary, whereas the pancreas and the skeletal muscle were unreactive, which is in line with previously published results. Next, both tumor cell- and stromal cell-associated KLK6 immunoexpression were analyzed in tumor tissue specimens of 118 ovarian cancer patients. In multivariate Cox regression analysis, only stromal cell-associated expression, besides the established clinical parameters FIGO stage and residual tumor mass, was found to be statistically significant for OS and PFS [high vs. low KLK6 expression; hazard ratio (HR), 1.92; p=0.017; HR, 1.80; p=0.042, respectively]. These results indicate that KLK6 expressed by stromal cells may considerably contribute to the aggressiveness of ovarian cancer.
authors.affiliation: Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Munich, Germany.
authors.forename: Lina
authors.initials: L
authors.lastname: Seiz
authors.forename: Julia
authors.initials: J
authors.lastname: Dorn
authors.forename: Matthias
authors.initials: M
authors.lastname: Kotzsch
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.forename: Nicolai I
authors.initials: NI
authors.lastname: Grebenchtchikov
authors.forename: Apostolos
authors.initials: A
authors.lastname: Gkazepis
authors.forename: Barbara
authors.initials: B
authors.lastname: Schmalfeldt
authors.forename: Marion
authors.initials: M
authors.lastname: Kiechle
authors.forename: Jane
authors.initials: J
authors.lastname: Bayani
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Rupert
authors.initials: R
authors.lastname: Langer
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000276:immunology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007610:Kallikreins / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000906:Antibodies; C103551:KLK6 protein, human; D007610:Kallikreins