Summary 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. 643-650 © 2001 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1649, available online at http://www.idealibrary.com on http://www.bjcancer.comIn the present study, we have evaluated KLK5 mRNA expression in relation to patient survival and other clinicopathologic variables in epithelial ovarian carcinoma. Our results demonstrate that KLK5 is an independent prognostic marker of poor prognosis in a subset of patients with grade I/II tumours.
MATERIALS AND METHODS
Ovarian cancer specimens and patients142 consecutive patients with epithelial ovarian carcinoma were included in this study, with ages ranging from 25 to 80 with a median of 59 years. Patients underwent surgery and treatment for primary ovarian carcinoma at the Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, University of Turin, Turin, Italy between July, 1991 and April, 1999. Follow-up information (median follow-up period 48 months) was available for 138 patients, among whom 83 (60%) have relapsed and 55 (40%) died. Of the 142 ovarian adenocarcinomas, for which histological diagnosis was available, 64 (45%) were serous papillary, 26 (18%) endometrioid, 22 (16%) undifferentiated, 12 (8%) clear cell, 11 (8%) mucinous, 6 (4%) Mullerian and 1 (1%) was unclassified. Due to the relatively small sample size, the clear cell, mucinous and Mullerian types were combined into one category...
