Regular Article

British Journal of Cancer (2001) 84, 643–650. doi:10.1054/bjoc.2000.1649 www.bjcancer.com
Published online 27 February 2001

Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer

H Kim1,2, A Scorilas1,2, D Katsaros3, G M Yousef1,2, M Massobrio3, S Fracchioli3, R Piccinno3, G Gordini4 and E P Diamandis1,2

  1. 1Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave, Toronto, M5G 1X5, Canada
  2. 2Department of Laboratory Medicine and Pathobiology, University of Toronto, 100 College Street, Toronto, Ontario, M5G 1L5, Canada
  3. 3Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Turin, 10126, Italy
  4. 4Department of Pathology, S. Anna Hospital, Turin, 10126, Italy

Received 25 September 2000; Revised 6 December 2000; Accepted 7 December 2000.

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Abstract

Kallikrein gene 5 (KLK5, also known as KLK-L2), located on chromosome 19q13.4, is one of the newly identified members of the kallikrein gene family, which is a subgroup of the serine protease enzyme family. In normal human tissues, KLK5 is highly expressed in skin, mammary gland and testis. Preliminary RT-PCR analysis has indicated that KLK5 is expressed in a subset of ovarian tumours. We have thus hypothesized that KLK5 may be a new prognostic indicator in ovarian cancer. We have examined the mRNA expression of KLK5 in 142 malignant ovarian tissues. Tumours were pulverized, total RNA was extracted, and cDNA was prepared by reverse transcription. KLK5 was amplified by PCR using gene specific primers, and the identity of the PCR product was verified by sequencing. Ovarian tissues were then classified as KLK5 positive or negative, based on ethidium bromide staining of the PCR product on agarose gels. KLK5 was found to be highly expressed in 58/142 (41%) of ovarian cancer samples while its level of expression was very low in normal ovarian tissues. We found a strong positive relation between KLK5 expression and tumour grade (P = 0.006) and disease stage (P = 0.027). Univariate survival analysis revealed that patients with ovarian tumours positive for KLK5 expression had an increased risk for relapse and death (P = 0.018 and 0.022, respectively). In multivariate analysis, KLK5 expression showed independent prognostic value only in the subset of tumours with lower grade disease (grades I and II). We conclude that KLK5 expression is associated with more aggressive forms of epithelial ovarian carcinoma and has indepdent prognostic value in low grade tumours. © 2001 Cancer Research Campaign

Keywords:

kallikrein gene 5, ovarian carcinoma, gene expression, survival analysis, prognostic markers, human kallikreins

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