The cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors

TitleThe cytoskeleton regulatory protein hMena (ENAH) is overexpressed in human benign breast lesions with high risk of transformation and human epidermal growth factor receptor-2-positive/hormonal receptor-negative tumors
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2006
AuthorsDi Modugno, F., Mottolese M., Di Benedetto A., Conidi A., Novelli Flavia, Perracchio L., Venturo I., Botti C., Jager E., Santoni A., Natali P.G., and Nisticò P.
JournalClinical Cancer Research
Volume12
Pagination1470-1478
ISSN10780432
Keywords80 and over, adolescent, adult, aged, and Medullary, Antibodies, article, benign tumor, Biological, breast, breast carcinogenesis, Breast Neoplasms, breast tumor, cancer cell culture, cancer risk, Carcinoma, Carcinoma in Situ, cell proliferation, cell strain MCF 7, Cell Transformation, Cohort studies, controlled study, Cytoskeletal Proteins, cytoskeleton protein, Ductal, epidermal growth factor receptor 2, erbB-2, estrogen, estrogen receptor, Female, Flow cytometry, gene overexpression, human, human tissue, Humans, immunohistochemistry, Ki 67 antigen, Lobular, major clinical study, malignant transformation, Middle Aged, Monoclonal, Monoclonal antibody, Neoplasm Invasiveness, Neoplasms, Neoplastic, neu differentiation factor, Neuregulin-1, Papillary, priority journal, Progesterone, progesterone receptor, prognosis, Prospective Studies, protein expression, protein hMena, Receptor, Receptors, regulator protein, Risk Factors, trastuzumab, Tumor Markers, unclassified drug, Western blotting
Abstract

Purpose: hMena (ENAH), a cytoskeleton regulatory protein involved in the regulation of cell motility and adhesion, is overexpressed in breast cancer. The aim of this study was to define at what stage of breast carcinogenesis hMena is overexpressed and to correlate hMena overexpression with established prognostic factors in breast cancer, focusing on human epidermal growth factor receptor-2 (HER-2). Experimental Design: hMena expression was assessed immunohistochemically in a prospective cohort of cases (n = 360) encompassing a highly representative spectrum of benign breast diseases associated with different risk of transformation, in situ, invasive, and metastatic tumors. Correlations with conventional pathologic and prognostic variables, such as proliferation index, hormonal receptor status, and HER-2 overexpression, were also evaluated. In vitro experiments were done to study the effect of neuregulin-1 and Herceptin treatments on hMena expression. Results: hMena protein is undetectable in normal breast and is weakly expressed in a small percentage of low-risk benign diseases (9%), but displays a progressive and significant increase of positivity in benign lesions at higher risk of transformation (slightly increased risk 43%; moderate increased risk 67%), in in situ (72%), invasive (93%), and metastatic breast cancer (91%). A significant direct correlation with tumor size (P = 0.04), proliferation index (P < 0.0001), and HER-2 overexpression (P < 0.0001) and an inverse relationship with estrogen (P = 0.036) and progesterone receptors (P = 0.001) are found in invasive carcinomas. In vitro experiments show that neuregulin-1 up-regulates, whereas Herceptin down-regulates, hMena expression. Conclusions: Our data provide new insights into the relevance of actin-binding proteins in human breast carcinogenesis and indicate hMena overexpression as a surrogate indicator in breast disease management. © 2006 American Association for Cancer Research.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-33645048173&doi=10.1158%2f1078-0432.CCR-05-2027&partnerID=40&md5=2e258be06f1fb4ef651a93af5e41fdea
DOI10.1158/1078-0432.CCR-05-2027