title: Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type.
abstract: Actinin-4 is an isoform of non-muscular alpha-actinin and actin-bundling protein. By enhancing cell motility, actinin-4 shows different biological properties from another isoform of non-muscular actinin 'actinin-1' and variable clinicopathological implications of actinin-4 have been demonstrated in some human malignancies such as breast cancers, lung cancers, and colorectal cancers. We herein described the clinicopathological and prognostic significance of actinin-4 expression in ovarian cancers. Actinin-4 expression was analyzed immunohistochemically in 265 primary ovarian carcinomas: 116 serous, 71 clear cell, 43 endometrioid, and 35 mucinous adenocarcinomas. With reference to endothelial immunoreactivity, cytoplasmic expression of actinin-4 was classified as either low (including negative) or high. Then, various parameters such as patients' characteristics, histopathological findings including E-cadherin and beta-catenin immunoreactivity, and clinical outcome, were compared between groups showing differences in the intensity or intracellular distribution of actinin-4 immunoreactivity. High expression of actinin-4 was demonstrated in 137 (57%) cases and was associated with serous histology (P=0.0075), high histological grade (P<0.0001), an advanced disease stage (P=0.036), a high degree of residual disease after initial surgery (P=0.0047), poor patient outcome (5-year survival: 52.4% in the high-expression group vs 71.9% in the low expression group, P=0.0043 by log-rank test), and also with reduced E-cadherin and preserved beta-catenin expressions (P=0.0097 and 0.017, respectively). Nuclear immunoreactivity for actinin-4 was detected in 20 (7.5%) cases and was associated with low histological grade (P=0.0079) but not with other variables. Multivariate analysis showed that high actinin-4 expression was an independent prognostic factor for overall survival, as well as a high degree of residual disease and clear-cell histology. Accumulation of actinin-4 in the cytoplasm may be related to a higher propensity for tumor invasiveness and metastasis, probably by enhancing cell motility, and could be a novel prognostic indicator for patients with ovarian carcinomas.
authors.affiliation: Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan.
authors.forename: Sohei
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Kita
authors.forename: Masashi
authors.initials: M
authors.lastname: Takano
authors.forename: Seiichi
authors.initials: S
authors.lastname: Tamai
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
mesh_terms: D000185:Actinin / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008840:Microfilament Proteins / Q000096:biosynthesis*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D046888:Tissue Array Analysis; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: C111453:ACTN4 protein, human; D014408:Biomarkers, Tumor; D015820:Cadherins; D008840:Microfilament Proteins; D051176:beta Catenin; D000185:Actinin