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


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.
Jahan
I
I
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 1-1 Yanagido, Gifu City 501-1194, Japan.
Fujimoto
J
J
Alam
S Mahfuzul
SM
Sato
E
E
Sakaguchi
H
H
Tamaya
T
T
D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D044464:Receptor, PAR-2 / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D015854:Up-Regulation
D012333:RNA, Messenger; D044464:Receptor, PAR-2