Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients

TY - JOUR

T1 - Stromal cell-associated expression of kallikrein-related peptidase 6 (KLK6) indicates poor prognosis of ovarian cancer patients

AU - Seiz, Lina

AU - Dorn, Julia

AU - Kotzsch, Matthias

AU - Walch, Axel

AU - Grebenchtchikov, Nicolai I

AU - Gkazepis, Apostolos

AU - Schmalfeldt, Barbara

AU - Kiechle, Marion

AU - Bayani, Jane

AU - Diamandis, Eleftherios P

AU - Langer, Rupert

AU - Sweep, Fred C G J

AU - Schmitt, Manfred

AU - Magdolen, Viktor

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Kallikreins

KW - Middle Aged

KW - Ovarian Neoplasms

KW - Prognosis

KW - Stromal Cells

KW - Survival Analysis

KW - Young Adult

U2 - 10.1515/hsz-2011-0264

DO - 10.1515/hsz-2011-0264

M3 - SCORING: Journal article

C2 - 22505521

VL - 393

SP - 391

EP - 401

JO - BIOL CHEM

JF - BIOL CHEM

SN - 1431-6730

IS - 5

ER -