Unfavorable prognostic value of human kallikrein 7 quantified by ELISA in ovarian cancer cytosols.
BACKGROUND
Human tissue kallikrein 7 (gene, KLK7; protein, hK7) is a member of the kallikrein family of secreted serine proteases. Reports indicate that in ovarian cancer, KLK7 is significantly up-regulated at the mRNA level. The aim of this study was to determine whether hK7, measured quantitatively by ELISA in ovarian cancer cytosols, is a prognostic biomarker for ovarian cancer.


METHODS
We used a newly developed ELISA with 2 monoclonal antibodies to quantify hK7 production in 260 ovarian tumor cytosols and correlated these data with various clinicopathologic variables and patient outcomes [progression-free survival (PFS) and overall survival (OS)] over a median follow-up period of 52 months.


RESULTS
Median (range) hK7 concentration in ovarian tumor cytosols was 2.84 (0-32.8) ng/mg of total protein. Compared with healthy and benign ovarian tissues and nonovarian tumors that metastasized to the ovary, malignant ovarian tumor cytosols highly overproduced hK7 (P <0.001). We used the median value as the cutoff value to categorize tumors as hK7-positive and hK7-negative. Women with hK7-positive tumors most frequently had advanced-stage disease, higher tumor grade (G3), suboptimal debulking, and serous or undifferentiated histotype (P <0.001). Univariate analysis showed that hK7 positivity was associated with significantly shorter PFS (P = 0.01) but not OS. Kaplan-Meier survival curves confirmed an increased risk of relapse in women with hK7-positive tumors (P = 0.009). In multivariate analysis, hK7 was not significantly associated with either PFS or OS.


CONCLUSIONS
hK7 is associated with other unfavorable characteristics of ovarian cancer, but it is not an independent prognosticator for ovarian cancer.
Shan
Shannon J C
SJ
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Scorilas
Andreas
A
Katsaros
Dionyssios
D
Rigault de la Longrais
Irene
I
Massobrio
Marco
M
Diamandis
Eleftherios P
EP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D003600:Cytosol / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007610:Kallikreins / Q000032:analysis*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000401:mortality; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; C082472:KLK7 protein, human; D007610:Kallikreins