title: Downregulation of the transcription factor, FoxD3, is associated with lymph node metastases in invasive ductal carcinomas of the breast.
abstract: FoxD3 is a transcription factor of the forkhead gene family. We investigated its expression in invasive ductal carcinomas (IDC) of the breast and its association with metastasis. The expression of FoxD3, human epidermal growth factor receptor-2 (HER-2), estrogen receptor (ER), progesterone receptor (PR) and Ki67 was examined by immunohistochemistry in samples from 121 patients with IDC. Non-tumorous breast adenosis tissues served as controls. HER2 expression was confirmed by fluorescence in situ hybridization (FISH). The expression levels of FoxD3 in IDC tissues and the breast cancer cell lines MCF-7 and MDA-MB-231 were additionally measured by western blotting. A greater percentage of total IDC patients and patients with lymph node metastases showed reduced FoxD3 expression compared to adenosis controls (p<0.05). Overall, FoxD3 was associated with metastatic status of IDC but not with age, pathological or clinical staging, or status of HER-2, ER, or PR. In particular, FoxD3 protein expression was down-regulated in the tumor epithelia of IDC samples from patients with metastases. Furthermore, FoxD3 protein expression was decreased in the metastatic MDA-MB-231 breast cancer cell line relative to the non-metastatic cell line, MCF-7. A greater number of patients with invasive, triple-negative breast cancer were also negative for FoxD3 expression than in other, non-triple-negative tumor types. These results suggest an inverse relationship between FoxD3 expression and tumor metastasis and warrants further investigation.
authors.affiliation: Department of Pathology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University Wuxi, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Pathology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University Wuxi, China.
authors.forename: Daozhen
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pathology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University Wuxi, China.
authors.forename: Jiayuan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University Wuxi, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Gynecology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University Wuxi, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Gynecology, The Affiliated Maternity and Child Health Hospital of Nanjing Medical University Wuxi, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D051858:Forkhead Transcription Factors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C503514:FOXD3 protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; FoxD3; HER-2; invasive ductal carcinomas