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1 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, M5G 1X5 Canada.
2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5G 1L5 Canada.
3 National Center of Scientific Research Demokritos, IPC, Athens, Greece 15310.
4 Academic Division of Gynecological Oncology, University of Turin, Mauriziano Umberto Hospital and Institute for Cancer Research and Treatment (IRCC) of Candiolo, Turin, Italy.
aAuthor for correspondence. Fax 416-586-8628; e-mail ediamandis{at}tsinai.on.ca.
Background: KLK5 is a newly discovered human kallikrein gene. Many kallikrein genes have been found to be differentially expressed in various malignancies, and prostate-specific antigen (PSA; encoded by the KLK3 gene) is the best tumor marker for prostate cancer. Like the genes that encode PSA and other kallikreins, the KLK5 gene was found to be regulated by steroid hormones in the BT-474 breast cancer cell line.
Methods: We studied KLK5 expression in 179 patients with different stages and grades of epithelial breast carcinoma by quantitative reverse transcription-PCR (RT-PCR), using LightCycler® technology. An optimal cutoff point equal to the detection limit (65th percentile) was used. KLK5 values were then compared with other established prognostic factors in terms of disease-free (DFS) and overall survival (OS).
Results: High KLK5 expression was found more frequently in pre-/perimenopausal (P = 0.026), node-positive (P = 0.029), and estrogen receptor-negative (P = 0.038) patients. In univariate analysis, KLK5 overexpression was a significant predictor of reduced DFS (P <0.001) and OS (P <0.001). Cox multivariate analysis indicated that KLK5 was an independent prognostic factor for DFS and OS. KLK5 remained an independent prognostic variable in the subgroups of patients with large tumors (>2 cm) and positive nodes. Hazard ratios derived from Cox analysis and related to DFS and OS were 2.48 (P = 0.005) and 2.37 (P = 0.009), respectively, for the node-positive group and 3.03 (P = 0.002) and 2.94 (P = 0.002), respectively, for patients with tumor sizes >2 cm. KLK5 expression was also associated with statistically significantly shorter DFS (P = 0.006) and OS (P = 0.004) in the subgroup of patients with grade I and II tumors.
Conclusions: KLK5 expression as assessed by quantitative RT-PCR is an independent and unfavorable prognostic marker for breast carcinoma.
The following articles in journals at HighWire Press have cited this article:
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  V. Kulasingam and E. P. Diamandis Proteomics Analysis of Conditioned Media from Three Breast Cancer Cell Lines: A Mine for Biomarkers and Therapeutic Targets Mol. Cell. Proteomics, November 1, 2007; 6(11): 1997 - 2011. [Abstract] [Full Text] [PDF]
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 F. R. Fritzsche, E. Dahl, S. Pahl, M. Burkhardt, J. Luo, E. Mayordomo, T. Gansukh, A. Dankof, R. Knuechel, C. Denkert, et al. Prognostic Relevance of AGR2 Expression in Breast Cancer. Clin. Cancer Res., March 15, 2006; 12(6): 1728 - 1734. [Abstract] [Full Text] [PDF]
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I. P. Michael, G. Sotiropoulou, G. Pampalakis, A. Magklara, M. Ghosh, G. Wasney, and E. P. Diamandis Biochemical and Enzymatic Characterization of Human Kallikrein 5 (hK5), a Novel Serine Protease Potentially Involved in Cancer Progression J. Biol. Chem., April 15, 2005; 280(15): 14628 - 14635. [Abstract] [Full Text] [PDF]
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 C. A. Borgono, I. P. Michael, and E. P. Diamandis Human Tissue Kallikreins: Physiologic Roles and Applications in Cancer Mol. Cancer Res., May 1, 2004; 2(5): 257 - 280. [Abstract] [Full Text] [PDF]
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K. Shigemasa, L. Gu, H. Tanimoto, T. J. O'Brien, and K. Ohama Human Kallikrein Gene 11 (KLK11) mRNA Overexpression Is Associated with Poor Prognosis in Patients with Epithelial Ovarian Cancer Clin. Cancer Res., April 15, 2004; 10(8): 2766 - 2770. [Abstract] [Full Text] [PDF]
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G. Kristiansen, K.-J. Winzer, E. Mayordomo, J. Bellach, K. Schluns, C. Denkert, E. Dahl, C. Pilarsky, P. Altevogt, H. Guski, et al. CD24 Expression Is a New Prognostic Marker in Breast Cancer Clin. Cancer Res., October 15, 2003; 9(13): 4906 - 4913. [Abstract] [Full Text] [PDF]
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 A. R. Falsey, M. A. Formica, J. J. Treanor, and E. E. Walsh Comparison of Quantitative Reverse Transcription-PCR to Viral Culture for Assessment of Respiratory Syncytial Virus Shedding J. Clin. Microbiol., September 1, 2003; 41(9): 4160 - 4165. [Abstract] [Full Text] [PDF]
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 G. M. Yousef, M.-E. Polymeris, L. Grass, A. Soosaipillai, P.-C. Chan, A. Scorilas, C. Borgono, N. Harbeck, B. Schmalfeldt, J. Dorn, et al. Human Kallikrein 5: A Potential Novel Serum Biomarker for Breast and Ovarian Cancer Cancer Res., July 15, 2003; 63(14): 3958 - 3965. [Abstract] [Full Text] [PDF]
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 E. P. Diamandis and G. M. Yousef Human Tissue Kallikreins: A Family of New Cancer Biomarkers Clin. Chem., August 1, 2002; 48(8): 1198 - 1205. [Abstract] [Full Text] [PDF]
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