Human kallikrein 13 protein in ovarian cancer cytosols: a new favorable prognostic marker

J Clin Oncol. 2004 Feb 15;22(4):678-85. doi: 10.1200/JCO.2004.05.144.

Abstract

Purpose: Human kallikrein 13 (hK13; encoded by the KLK13 gene) is a secreted serine protease expressed in endocrine tissues, including the prostate, testis, breast, and ovary. We have previously reported steroid hormone regulation of the KLK13 gene and its clinical value as a marker of favorable prognosis in breast cancer at the mRNA level. We hypothesized that hK13 may represent a potential biomarker for ovarian carcinomas.

Patients and methods: Using a newly developed enzyme-linked immunosorbent assay (ELISA), hK13 levels were quantified in 131 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: hK13 concentration in ovarian tumor cytosols ranged from 0 to 18.4 ng/mg of total protein. An optimal cutoff value of 0.13 ng/mg (67(th) percentile) was selected, based on the ability of hK13 values to predict the PFS of the study population, to categorize tumors as hK13-positive or negative. Women with hK13-positive tumors most often had early stage (stage I/II) disease, no residual tumor after surgery and optimal debulking success (P <.05). Univariate and multivariate Cox regression analyses revealed that patients with hK13-positive tumors had a significantly longer PFS and OS than hK13-negative patients (P <.05). Kaplan-Meier survival curves further confirmed a reduced risk of relapse and death in women with hK13-positive tumors (P =.007 and P =.002, respectively).

Conclusion: These results indicate that hK13 is an independent marker of favorable prognosis in ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Cytosol / metabolism*
  • Disease-Free Survival
  • Female
  • Humans
  • Kallikreins / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / mortality
  • Proportional Hazards Models
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • KLK13 protein, human
  • Kallikreins