title: Expression and intracellular localization of FKHRL1 in mammary gland neoplasms.
abstract: FKHRL1 (FOXO3a), a member of the Forkhead family of genes, has been considered to be involved in the development of breast tumors; however, the in vivo expression and activation status of FKHRL1 in breast tumors still remains unclear. We immunohistochemically demonstrated the expression and intracellular localization of FKHRL1 in human breast tumors by the novel anti-FKHRL1 antibody which is available for formalin-fixed paraffin-embedded specimens. In a total of 51 cases of benign tumors, FKHRL1 was diffusely expressed in all cases, and its intracellular localization was revealed to be cytoplasmic (inactive form) in 94% of cases of intraductal papillomas (16/17) and 91% cases of fibroadenomas (31/34), with a similar pattern to normal glandular epithelium. In invasive ductal carcinomas, 83% of the cases (93/112) diffusely expressed FKHRL1; however, unlike benign tumors, 71% of the cases (66/93) showed the nuclear-targeted, active form of FKHRL1. Moreover, activated FKHRL1 was predominantly observed in scirrhous (29/36, 81% of the cases) and papillotubular (30/38, 79% of the cases) subtypes, compared to the solid-tubular subtype (7/19, 37% of the cases). Furthermore, the cases with nuclear-targeted FKHRL1 showed a tendency to have lymph nodal metastasis with statistical significance (P < 0.0001). Thus, the activation of FKHRL1 seems to be recognized as one of the specific features of invasive ductal carcinoma of the breast.
authors.affiliation: Department of Pathology, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
authors.forename: Gui-Shan
authors.initials: GS
authors.lastname: Jin
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Miyake
authors.forename: Masao
authors.initials: M
authors.lastname: Shibata
authors.forename: Takako
authors.initials: T
authors.lastname: Takashima
authors.forename: Yi-Xuan
authors.initials: YX
authors.lastname: Liu
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Akagi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D000328:Adult; D000818:Animals; D000906:Antibodies; D001943:Breast Neoplasms / Q000473:pathology / Q000503:physiopathology*; D018270:Carcinoma, Ductal, Breast / Q000503:physiopathology / Q000556:secondary; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005260:Female; D018226:Fibroadenoma / Q000473:pathology / Q000503:physiopathology; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018300:Papilloma, Intraductal / Q000503:physiopathology* / Q000556:secondary; D016612:Paraffin Embedding; D011817:Rabbits; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; C499517:FOXO3 protein, human; D000071161:Forkhead Box Protein O1; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D014157:Transcription Factors