title: Overexpression of osteopontin independently correlates with vascular invasion and poor prognosis in patients with hepatocellular carcinoma.
abstract: This study retrospectively evaluated the immunohistochemical expression of 3 cell adhesion molecules (CAMs), E-cadherin, beta-catenin, and osteopontin, according to tumor grade in 125 surgically resected specimens of hepatocellular carcinoma (HCC). The aims of this study were to identify factors associated with vascular invasion and to elucidate the prognostic value of CAMs. The median follow-up time was 110 months. The levels of E-cadherin, beta-catenin, and osteopontin immunoreactivity were significantly associated with Edmondson-Steiner grade but not with tumor size. There was increased loss of E-cadherin, nonnuclear overexpression of beta-catenin, and overexpression of osteopontin in tumors of higher histologic grade. Vascular invasion was found in 44 (35%) of 125 resected specimens. Logistic regression analysis identified 3 tumor-related factors that were independently associated with vascular invasion-tumor size more than 3 cm, Edmondson-Steiner grades III to IV, and overexpression of osteopontin. Among the tested CAMs, osteopontin (P = .0110) and E-cadherin (P = .0287) were significant prognostic factors by univariate analysis. The Cox proportional hazard regression analysis revealed that Edmondson-Steiner grades III to IV (relative risk [RR], 3.028; P < .001), the presence of vascular invasion (RR, 1.964; P = .011), overexpression of osteopontin (RR, 1.755; P = .034), serum alpha-fetoprotein level more than 20 ng/mL (RR, 1.834; P = .037), and Child-Pugh classification B to C (RR, 1.880; P = .040) were found to be independently significant factors associated with survival after hepatectomy. These results suggest that overexpression of osteopontin independently correlates with vascular invasion and thus predicts poor survival for patients with HCC, whereas aberrant expression of E-cadherin or beta-catenin does not.
authors.affiliation: Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan.
authors.forename: Pavel V
authors.initials: PV
authors.lastname: Korita
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shirai
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Matsuda
authors.forename: Jun
authors.initials: J
authors.lastname: Sakata
authors.forename: Xing
authors.initials: X
authors.lastname: Cui
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hatakeyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006498:Hepatectomy; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D053495:Osteopontin / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D055815:Young Adult; D051176:beta Catenin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D051176:beta Catenin; D053495:Osteopontin