title: Expression and prognostic significance of kallikrein-related peptidase 8 protein levels in advanced ovarian cancer by using automated quantitative analysis.
abstract: Kallikrein-related peptidases, a subgroup of the serine protease enzyme family, are considered to be important prognostic biomarkers in cancer. In this study we sought to determine the prognostic value of kallikrein-related peptidase 8 (KLK8, hK8, KLK-8) in ovarian cancer using a novel method of compartmentalised in situ protein analysis. A tissue array composed of 150 advanced stage ovarian cancers, uniformly treated with surgical debulking followed by platinum-paclitaxel combination chemotherapy, was constructed. For the evaluation of kallikrein-related peptidase 8 protein expression, we used an immunofluorescence-based method of automated in situ quantitative protein analysis (AQUA). Mean follow-up time of the cohort was 34.35 months. One hundred twenty-six of 150 cases had sufficient tissue for AQUA analysis. There were significant correlations between tumour mask KLK8 protein expression levels and clinicopathological variables, including grade (p = 0.0011), residual disease (p = 0.0063) and clinical response to chemotherapy(p = 0.0346). In univariate survival analysis there was a significant correlation between KLK8 tumour mask expression and five years progression-free survival, meanwhile it was not associated with five-year overall survival (p = 0.0694). Specifically, low KLK8 expression correlated with better outcome (top vs. bottom quartile, p = 0.0319). In multivariate survival analysis, adjusting for well-characterised prognostic variables, tumour KLK8 expression level retained its prognostic significance for progression-free survival (95%CI: 0.341-1.027, p = 0.045). The possibility that KLK8 may be a suitable candidate as a diagnostic and prognostic marker warrants further investigation.
authors.affiliation: Yale Cancer Center, PO Box 208032, New Haven, CT 06520, USA.
authors.forename: Panteleimon
authors.initials: P
authors.lastname: Kountourakis
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.forename: Sonia
authors.initials: S
authors.lastname: Markakis
authors.forename: Diane
authors.initials: D
authors.lastname: Kowalski
authors.forename: Robert L
authors.initials: RL
authors.lastname: Camp
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: Meletios A
authors.initials: MA
authors.lastname: Dimopoulos
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000032:analysis* / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000473:pathology; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods*; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; C094799:KLK8 protein, human; D007610:Kallikreins