Human kallikrein 11: an indicator of favorable prognosis in ovarian cancer patients.
OBJECTIVE
Human kallikrein 11 (hK11) is a secreted serine protease, highly expressed in hormonally regulated tissues, including the prostate and the ovary. Our preliminary studies indicate that hK11 may represent a diagnostic and prognostic biomarker for ovarian cancer. The aim of the present study was to examine the prognostic value of hK11 expression in ovarian tumors.


METHODS
Using our established immunofluorometric assay, hK11 levels were quantified (ng per mg of total protein) in 134 ovarian tumor extracts and correlated with various clinicopathological variables and outcome [progression-free survival (PFS), overall survival (OS)], over a median follow-up period of 42 months.


RESULTS
hK11 concentration in ovarian tumor cytosols ranged from 0 to 155 ng/mg of total protein, with a median of 1.45 ng/mg. An optimal cutoff value of 6.3 ng/mg was selected to categorize tumors as hK11-positive or negative. hK11-positive tumors were most often of early stage (Stage I/II) and grade (G1/G2) (P < 0.05). Univariate analysis revealed that patients with hK11-positive tumors had a significantly longer PFS (HR of 0.39, P = 0.005) and OS (HR of 0.44, P = 0.033). Cox multivariate analysis indicated that hK11 was an independent prognostic indicator of PFS (HR of 0.47, P = 0.042). Kaplan-Meier survival curves further confirmed that women with hK11-positive tumors have longer PFS and OS (P = 0.003 and P = 0.028, respectively). Also, a weak positive correlation was found between the expression levels of tissue hK11 and tissue CA125 (rs = 0.508; P < 0.001).


CONCLUSIONS
These results further validate our initial findings that hK11 is an independent marker of favorable prognosis in ovarian cancer patients.
Diamandis
Eleftherios P
EP
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, M5G 1X5, Canada. ediamandis@mtsinai.on.ca
Borgoño
Carla A
CA
Scorilas
Andreas
A
Harbeck
Nadia
N
Dorn
Julia
J
Schmitt
Manfred
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012697:Serine Endopeptidases / Q000032:analysis* / Q000096:biosynthesis*; D018709:Statistics, Nonparametric
C114880:trypsin-like serine protease; D012697:Serine Endopeptidases