Expression of the serine protease matriptase and its inhibitor HAI-1 in epithelial ovarian cancer: correlation with clinical outcome and tumor clinicopathological parameters.
OBJECTIVE
Matriptase is a type II transmembrane serine protease expressed by cells of surface epithelial origin, including epithelial ovarian tumor cells. Matriptase cleaves and activates proteins implicated in the progression of ovarian cancer and represents a potential prognostic and therapeutic target. The aim of this study was to examine the expression of matriptase, and its inhibitor, hepatocyte growth factor activator inhibitor-1 (HAI-1), in epithelial ovarian cancer and to assign clinicopathological correlations.


METHODS
We have determined by immunohistochemistry the expression of matriptase and HAI-1 in 54 epithelial ovarian cancers. Statistical analyses of immunohistochemistry expression data with clinical outcome and clinicopathological parameters were then performed.


RESULTS
Of 54 tumors tested, 39 (72%) and 11 (20%) were positive for matriptase and for HAI-1, respectively. All HAI-1-positive tumors were also matriptase positive. Analysis of clinicopathological parameters demonstrated a loss of matriptase associated with stage III/IV tumors as compared with stage I/II tumors (P = 0.030). There was also a loss of HAI-1 expression associated with stage III/IV tumors (P = 0.039). Of 34 stage I/II tumors, 28 (82%) stained positive for matriptase, and 10 (29%) stained positive for HAI-1; 10 (29%) tumors showed coexpression. Of 20 stage III/IV tumors, however, 11 stained positive for matriptase (55%), only 1 of which coexpressed HAI-1 (P = 0.039).


CONCLUSIONS
Advanced-stage ovarian tumors that express matriptase are more likely to do so in the absence of its inhibitor, HAI-1, indicating that an imbalance in the matriptase:HAI-1 ratio could be important in the development of advanced disease. Such an imbalance could promote the proteolytic activity of matriptase and, consequently, a more invasive phenotype.
Oberst
Michael D
MD
Department of Oncology, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA.
Johnson
Michael D
MD
Dickson
Robert B
RB
Lin
Chen-Yong
CY
Singh
Baljit
B
Stewart
Moira
M
Williams
Alastair
A
al-Nafussi
Awatif
A
Smyth
John F
JF
Gabra
Hani
H
Sellar
Grant C
GC
D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016016:Proportional Hazards Models; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012697:Serine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D016019:Survival Analysis; D014357:Trypsin / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; C109149:SPINT1 protein, human; D012697:Serine Endopeptidases; C485595:matriptase; C485596:ST14 protein, human; D014357:Trypsin