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Annals of Oncology 2007 18(9):1506-1512; doi:10.1093/annonc/mdm190
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© 2007 European Society for Medical Oncology

gynecologic tumors

Role of protease activated receptor-2 in tumor advancement of ovarian cancers

I Jahan, J Fujimoto*, S. Mahfuzul Alam, E Sato, H Sakaguchi and T Tamaya

Department of Obstetrics and Gynecology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan

* Correspondence to: Dr J. Fujimoto, Department of Obstetrics and Gynecology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan. Tel: +81 58 230 6349; Fax: +81 58 230 6348; E-mail: jf{at}cc.gifu-u.ac.jp

Background: Protease activated receptor-2 (PAR-2) has been implicated in cellular proliferation, invasion and metastasis with angiogenesis in various tumors. This prompted us to study the role of PAR-2 in tumor advancement of ovarian cancers.

Materials and methods: Forty-eight patients underwent surgery for ovarian cancers. In ovarian cancers, PAR-2 histoscores and mRNA levels were determined by immunohistochemistry and real-time reverse transcription-polymerase chain reaction, respectively. Patient prognosis was analysed with a 36-month survival rate. Microvessel counts were determined by immunohistochemistry for CD31 and factor VIII-related antigen and the rate of cell proliferation was determined by immunohistochemistry for Ki67.

Results: Immunohistochemical staining revealed distribution of PAR-2, dominantly in cancer cells and faintly in stromal cells of the tumor. PAR-2 histoscores in cancer cells and mRNA levels both significantly increased in ovarian cancers with clinical stages (I < II < III < IV, P < 0.05), regardless of histopathological type. The 36-month survival rate of 24 patients with high PAR-2 was poor (58%), while that of the other 24 patients with low PAR-2 was significantly higher (83%). There were significant correlations between PAR-2 histoscores in cancer cells and mRNA levels with microvessel counts and with the rate of cell proliferation in ovarian cancers.

Conclusions: PAR-2 was up-regulated during ovarian cancer progression. Therefore, PAR-2 might work on tumor advancement of ovarian cancers via angiogenic activity and is considered to be a novel prognostic indicator in ovarian cancers.

Key words: PAR-2, ovarian cancer, angiogenesis, prognostic indicator, tumor advancement

Received for publication December 11, 2006. Revision received April 9, 2007. Accepted for publication April 11, 2007.


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