Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer

Ko, Kang Young; Choi, Hyun; Lee, Seon Kyung; Kim, Seung Bo; Park, Yong Gu; Ji, Sung Gil

Abstract

OBJECTIVE
The purposes of this study were to examine the expression of matriptase, and its inhibitor, HAI-1, in epithelial ovarian cancer and to assign clinicopathological correlations and to discuss the matriptase/inhibitor (HAI-1) system in the context of ovarian cancer and to examine the possibility that this system might be a useful therapeutic target in this disease.
METHODS
A retrospective study was performed in 51 patients with primary epithelial ovarian cancer staged over Ic who have been diagnosed and treated at Kyung Hee university medical center from Jan. 1991 to Mar. 2003. They were managed with cytoreductive surgery and chemotherapy. This study was performed in paraffin embedded blocks of primary epithelial ovarian cancer of 51 patients by means of immunohistochemistry. In addition, to validate protein expression data at the gene level, matriptase/HAI-1 mRNA expression was evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR) on frozen specimens from 10 ovarian cancers. Statistical analyses of immunohistochemistry (IHC) expression data with clinicopathological parameters and survival were then performed.
RESULTS
Of 51 ovarian tumors tested, 25 (49%) and 37 (72.5%) were positive staining for matriptase and HAI-1 by IHC, respectively. Of 18 stage I/II tumors, 11 (61.1%) stained positive for matriptase, and 15 (83.3%) stained positive for HAI-1; Of 18 stage I/II tumors, 10 (55.6%) tumors showed coexpression. Of 33 stage III/IV tumors, 14 (42.4%) stained positive for matriptase and 22 (66.7%) stained positive for HAI-1; Of 33 stage III/IV tumors, 11 (33.3%) tumors showed coexpression.
CONCLUSION
No relationship was found between the expression of either matriptase or HAI-1 with clinicopathological parameters and survival. However, stage I/II ovarian tumors are more likely to express matriptase and HAI-1 than are the more advanced disease stage III/IV tumors. Correspondingly, the low frequency of matriptase and HAI-1 coexpression is more likely to be associated with stage III/IV tumors than stage I/II tumors. Such an imbalance in the matriptase: HAI-1 ratio could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype in the advanced tumors.