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Clinical Chemistry 52: 1070-1079, 2006. First published April 20, 2006; 10.1373/clinchem.2005.065599
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(Clinical Chemistry. 2006;52:1070-1079.)
© 2006 American Association for Clinical Chemistry, Inc.

Cancer Diagnostics

Quantitative Reverse Transcription-PCR Assay for Detection of mRNA Encoding Full-Length Human Tissue Kallikrein 7: Prognostic Relevance of KLK7 mRNA Expression in Breast Cancer 3

Leon Holzscheiter1, Julia C. Biermann1, Matthias Kotzsch2, Panagiotis Prezas3, Juliane Farthmann1, Gustavo Baretton2, Thomas Luther2,4, Vivianne C.G. Tjan-Heijnen5, Maroulio Talieri3, Manfred Schmitt1, Fred C.G.J. Sweep6, Paul N. Span6 and Viktor Magdolen1,a

1 Clinical Research Unit, Department of Obstetrics and Gynecology, Technical University of Munich, Munich, Germany.
2 Institute of Pathology, Technical University of Dresden, Dresden, Germany.
3 G Papanicolaou Research Center-Saint Savas Hospital, Athens, Greece.
4 Medical Laboratory Unit, Bautzen, Germany.
Departments of5 Medical Oncology and 6 Chemical Endocrinology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

aAddress correspondence to this author at: Klinische Forschergruppe der Frauenklinik der Technischen Universität München, Klinikum rechts der Isar, Ismaninger Strasse 22, D-81675 München, Germany. Fax 49-89-4140-7410; e-mail viktor.magdolen{at}lrz.tum.de.

Background: The human tissue kallikrein gene family (KLK1 to KLK15) encodes a group of 15 serine proteases (hK1 to hK15), several of which have been implicated in cancer-related processes.

Methods: We established a specific quantitative reverse transcription-PCR assay for full-length KLK7 mRNA that excluded amplification of the exon 2 deletion splice variant (the latter does not encode a functional protease), and evaluated full-length KLK7 mRNA expression [normalized to human glucose-6-phosphate dehydrogenase (h-G6PDH)] in tumor tissue specimens from 155 breast cancer patients.

Results: High KLK7 mRNA expression (continuous) was significantly associated with a better patient outcome according to both univariate (P = 0.005) and multivariate (P = 0.046) Cox survival analysis. Separation of patients by optimized dichotomization revealed a significantly better prognosis for patients with high KLK7 mRNA status (n = 89) compared with patients with low KLK7 mRNA status (n = 66) [univariate hazard ratio (HR) = 0.45 (P = 0.001); multivariate HR = 0.50 (P = 0.005)]. In the subgroup of patients not receiving adjuvant treatment (n = 69), KLK7 mRNA status was a significant prognosticator [univariate HR = 0.29 (P = 0.002); multivariate HR = 0.40 (P = 0.034)]. This subgroup was least influenced by postoperative treatment and thus best showed the impact of KLK7 expression on the natural course of breast cancer disease.

Conclusion: Expression of full-length KLK7 mRNA may represent a new prognostic marker in breast cancer disease.






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