Abstract
Many kallikrein genes were found to be differentially expressed in various malignancies, and prostate specific antigen (encoded by the
KLK3
gene) is the best tumour marker for prostate cancer. Prostate specific antigen has recently been shown to be an independent favourable prognostic marker for breast cancer.
KLK15
is newly discovered kallikrein gene that is located adjacent to
KLK3
on chromosome 19q13.4.
KLK15
has 41% similarity to
KLK3
and the encoded protein, hK15, can activate pro-prostate specific antigen. We studied the expression of
KLK15
by real-time quantitative reverse transcriptase–polymerase chain reaction in 202 tissues from patients with breast carcinoma of various stages, grades and histological types.
KLK15
expression was found to be a significant predictor of progression-free survival (hazard ratio of 0.41 and
P
=0.011) and overall survival (hazard ratio of 0.34 and
P
=0.009). When all other known confounders were controlled in the multivariate analysis,
KLK15
retained its prognostic significance. Higher concentrations of
KLK15
mRNA were found more frequently in node negative patients (
P
=0.042). No association was found between
KLK15
expression and any other clinicopathological variable. Further,
KLK15
is an independent prognostic factor of progression-free survival and overall survival in the subgroup of patients with lower grade and those with oestrogen receptor and progesterone receptor negative tumours in both univariate and multivariate analysis.
KLK15
levels of expression were slightly higher (although not statistically significant) in the oestrogen receptor negative and progesterone receptor negative subgroups of patients.
KLK15
is up-regulated by androgens in breast cancer cell lines. Time-course and blocking experiments suggest that this regulation is mediated through the androgen receptor.
British Journal of Cancer
(2002)
87
, 1294–1300. doi:
10.1038/sj.bjc.6600590
www.bjcancer.com
© 2002 Cancer Research UK