title: The androgen-regulated gene human kallikrein 15 (KLK15) is an independent and favourable prognostic marker for breast cancer.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: G M
authors.initials: GM
authors.lastname: Yousef
authors.forename: A
authors.initials: A
authors.lastname: Scorilas
authors.forename: A
authors.initials: A
authors.lastname: Magklara
authors.forename: N
authors.initials: N
authors.lastname: Memari
authors.forename: R
authors.initials: R
authors.lastname: Ponzone
authors.forename: P
authors.initials: P
authors.lastname: Sismondi
authors.forename: N
authors.initials: N
authors.lastname: Biglia
authors.forename: M
authors.initials: M
authors.lastname: Abd Ellatif
authors.forename: E P
authors.initials: EP
authors.lastname: Diamandis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005819:Genetic Markers; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013534:Survival; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D005819:Genetic Markers; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C501608:KLK15 protein, human; D007610:Kallikreins