title: Expression of human Kallikrein 14 (KLK14) in breast cancer is associated with higher tumour grades and positive nodal status.
abstract: Human kallikrein 14 (KLK14) is a steroid hormone-regulated member of the tissue kallikrein family of serine proteases, for which a prognostic and diagnostic value in breast cancer has been suggested. To further characterise the value of KLK14 as a breast tumour marker, we have carefully analysed KLK14 expression in normal breast tissue and breast cancer both on the RNA level by real-time RT-PCR (n = 39), and on the protein level (n = 127) using a KLK14-specific antibody for immunohistochemistry. We correlated KLK14 protein expression data with available clinico-pathological parameters (mean follow-up time was 55 months) including patient prognosis. KLK14 RNA expression as quantified by real-time RT-PCR was significantly more abundant in breast tumours compared to normal breast tissue (P = 0.027), an issue that had not been clarified recently. Concordantly with the RNA data, cytoplasmic KLK14 protein expression was significantly higher in invasive breast carcinomas compared to normal breast tissues (P = 0.003). Furthermore, KLK14 protein expression was associated with higher tumour grade (P = 0.041) and positive nodal status (P = 0.045) but was not significantly associated with shortened disease-free or overall patient survival time in univariate analyses. We conclude that KLK14 is clearly overexpressed in breast cancer in comparison to normal breast tissues and is positively associated with conventional parameters of tumour aggressiveness, but due to a missing association with survival times, the use of KLK14 immunohistochemistry as a prognostic marker in breast cancer is questionable.
authors.affiliation: Institute of Pathology, Department of Urology, Charité Universitätsmedizin, Berlin, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Fritzsche
authors.forename: T
authors.initials: T
authors.lastname: Gansukh
authors.forename: C A
authors.initials: CA
authors.lastname: Borgoño
authors.forename: M
authors.initials: M
authors.lastname: Burkhardt
authors.forename: S
authors.initials: S
authors.lastname: Pahl
authors.forename: E
authors.initials: E
authors.lastname: Mayordomo
authors.forename: K-J
authors.initials: KJ
authors.lastname: Winzer
authors.forename: W
authors.initials: W
authors.lastname: Weichert
authors.forename: C
authors.initials: C
authors.lastname: Denkert
authors.forename: K
authors.initials: K
authors.lastname: Jung
authors.forename: C
authors.initials: C
authors.lastname: Stephan
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: E P
authors.initials: EP
authors.lastname: Diamandis
authors.forename: E
authors.initials: E
authors.lastname: Dahl
authors.forename: G
authors.initials: G
authors.lastname: Kristiansen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000096:biosynthesis* / Q000502:physiology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C425336:KLK14 protein, human; D007610:Kallikreins