title: Immunohistochemical actinin-4 expression in infiltrating gliomas: association with WHO grade and differentiation.
abstract: Actinin-4 is an isoform of nonmuscular α-actinin and actin-bundling protein that plays an important role in cancer invasion and metastasis by enhancing cellular motility. Recent studies have revealed an association between several clinicopathological profiles and actinin-4 overexpression in human cancers. In this study, we investigated the immunohistochemical actinin-4 expression in 39 infiltrating gliomas. The specimens included three diffuse astrocytomas, three oligodendrogliomas, one oligoastrocytoma, two anaplastic astrocytomas, four anaplastic oligodendrogliomas, three anaplastic oligoastrocytomas, 17 glioblastomas, four gliosarcomas, and two glioblastomas with oligodendroglial component. All seven World Health Organization (WHO) grade II tumors were negative for actinin-4, whereas 20 of 22 tumors with strong actinin-4 expression were WHO grade IV. Actinin-4 expression was significantly associated with histological grade (P < 0.0001) and proliferative activity measured by Ki-67 staining (P = 0.0045). Notably, actinin-4 expression was more pronounced in high-grade astrocytic tumors than oligodendroglial tumors (P < 0.0001). Additionally, pseudopalisading cells in glioblastoma exhibited stronger actinin-4 expression than the rest, likely reflecting enhanced cellular motility in pseudopalisades. This study is the first to demonstrate significant correlation between actinin-4 expression and tumor grade using clinical glioma samples. Although diagnostic utility of this marker awaits future exploration, actinin-4 may help distinguish between astrocytic and oligodendroglial lines of differentiation.
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan, shfukush@ncc.go.jp.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Fukushima
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Honda
authors.forename: Akiko Miyagi
authors.initials: AM
authors.lastname: Maeshima
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Narita
authors.forename: Tesshi
authors.initials: T
authors.lastname: Yamada
authors.forename: Soichiro
authors.initials: S
authors.lastname: Shibui
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
mesh_terms: D000185:Actinin / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D013194:Staining and Labeling; D014407:Tumor Cells, Cultured; D014944:World Health Organization
chemical_list: C111453:ACTN4 protein, human; D019394:Ki-67 Antigen; D000185:Actinin