The prognostic value of the human kallikrein gene 9 (KLK9) in breast cancer.
BACKGROUND
Many members of the human kallikrein gene family were found to be differentially expressed in various malignancies and some of them are useful diagnostic/prognostic markers. KLK9 is a newly discovered human kallikrein gene that is expressed in several tissues including thymus, spinal cord, testis, prostate, breast, and ovary. Like other kallikreins, the KLK9 gene was found to be regulated by steroid hormones, mainly estrogens and progestins, in cancer cell lines.


METHODS
We studied the expression of KLK9 by quantitative RT-PCR in 169 breast cancer patients of different stages, grades and histological types. We also compared the relation between KLK9 expression and other clinicopathological variables and patient survival.


RESULTS
KLK9 expression is significantly higher in patients with early stage cancers (p = 0.039) and in patients with small tumor size (< 2 cm) (p = 0.028). Kaplan-Meier survival curves demonstrated that KLK9-positive patients have longer disease-free and overall survival (p = 0.015 and 0.036, respectively). Univariate and multivariate analysis also indicates that KLK9 expression is associated with increased disease-free and overall survival. When the Cox proportional hazard regression analysis was applied to subgroups of patients, KLK9 expression was found to be a significant predictor of disease-free survival in the estrogen receptor (ER) and progesterone receptor (PR) negative subgroups of patients (Hazard Ratio 'HR' = 0.28, and 0.38, respectively, and p = 0.011 and 0.028, respectively). After adjusting for other known prognostic variables, KLK9 retained its independent prognostic value in these subgroups of patients. Similar results were obtained for overall survival.


CONCLUSIONS
KLK9 is a new potential independent marker of favorable prognosis in breast cancer.
Yousef
George M
GM
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
Scorilas
Andreas
A
Nakamura
Terukazu
T
Ellatif
Mohamed Abd
MA
Ponzone
Riccardo
R
Biglia
Nicoletta
N
Maggiorotto
Furio
F
Roagna
Riccardo
R
Sismondi
Piero
P
Diamandis
Eleftherios P
EP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000628:therapy; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis / Q000235:genetics*; D008408:Mastectomy; D008875:Middle Aged; D009363:Neoplasm Proteins; D011237:Predictive Value of Tests; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C410801:KLK9 protein, human; D007610:Kallikreins