title: Human kallikrein 8 (hK8/TADG-14) expression is associated with an early clinical stage and favorable prognosis in ovarian cancer.
abstract: The purpose of this study was to examine human kallikrein 8 (hK8/TADG-14) expression in epithelial ovarian tumors and to investigate the association of hK8 expression levels with patient survival. Human kallikrein 8 protein (hK8) expression was examined by immunohistochemistry in 74 ovarian adenocarcinomas and 6 normal ovaries. Results of immunostaining were correlated with clinicopathological variables and overall survival of the patients. Human kallikrein 8 gene (KLK8) mRNA expression was examined by semi-quantitative PCR in 35 ovarian tumors and 7 normal ovaries. Expression of hK8 was not detected on the surface epithelium of normal ovaries. In contrast, hK8 expression was detected in 51.4% (38/74) of carcinomas with a significantly higher detection rate of hK8 expression being observed in early stage disease compared to advanced stage disease (p=0.0192). Data analysis using the log-rank test showed hK8 expression correlated significantly with favorable patient survival (p=0.0328). Younger age (p=0.0008), early clinical stage (p<0.0001), and low histological grades of the tumors (p=0.0018) were also associated significantly with a favorable prognosis. In a multivariate model, age (p=0.0186) and clinical stage (p<0.0001) remained associated significantly with overall survival, whereas hK8 expression and histological grade lost their significance. There was significant relationship between the hK8 expression status and KLK8 mRNA expression levels (p=0.0304). Expression of hK8 is increased during the development of ovarian cancer and down-regulated during ovarian cancer progression. Expression of hK8 is a favorable prognostic marker in patients with ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima 734-8551, Japan. kazu@hiroshima-u.ac.jp
authors.forename: Kazushi
authors.initials: K
authors.lastname: Shigemasa
authors.forename: Xiurong
authors.initials: X
authors.lastname: Tian
authors.forename: Lijun
authors.initials: L
authors.lastname: Gu
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Tanimoto
authors.forename: Lowell J
authors.initials: LJ
authors.lastname: Underwood
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: O'Brien
authors.forename: Koso
authors.initials: K
authors.lastname: Ohama
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C094799:KLK8 protein, human; D007610:Kallikreins