title: Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue.
abstract: Nerve growth factor receptor (NGFR) is a transmembrane glycoprotein without intrinsic tyrosine kinase activity, whose expression is not restricted to neural cells. NGFR is reported to act as a tumour suppressor, negatively regulating cell growth and proliferation. NGFR expression was immunohistochemically analysed in normal breast tissue and in 140 benign, biphasic and preinvasive breast lesions, in 22 tumours with myoepithelial differentiation and in two cohorts of breast cancer patients: a series of 245 invasive breast carcinomas studied with tissue microarrays and 37 high-grade invasive ductal carcinomas with basal-like immunophenotype. NGFR consistently displayed membrane reactivity in myoepithelial cells arranged as a continuous layer around normal ducts and lobular units, intralobular fibroblasts, vascular adventitia and nerve bundles. Myoepithelial cells of benign proliferations and pre-invasive lesions were consistently positive for NGFR. Scattered NGFR-positive cells were observed in solid areas of six out of nine cases of hyperplasia of usual type, whereas in flat atypia, lobular carcinoma in situ and virtually all cases of ductal carcinoma in situ (97.5%), NGFR was restricted to the myoepithelial layer. Positivity for NGFR was observed in 11 out of 245 (4.5%) breast carcinomas, nine out of 20 (45%) metaplastic breast carcinomas and 14 out of 37 (38%) basal-like breast carcinomas. NGFR expression in invasive tumours significantly correlated with that of cytokeratins 5/6 (P<0.05), 14 (P<0.0001) and 17 (P<0.0005) and EGFR (P<0.0001) and displayed an inverse correlation with oestrogen and progesterone receptors (both, P<0.0001). NGFR showed a statistically significant association with longer disease-free (P<0.05) and overall survival (P<0.01) in the cohort of patients with basal-like carcinomas. This study demonstrates the usefulness of NGFR as a new adjunct marker to identify myoepithelial cells in preinvasive lesions and myoepithelial differentiation in breast carcinomas. Furthermore, provisional data in a small number of basal-like breast carcinomas suggest that NGFR may identify a subgroup of basal-like breast carcinomas with good prognosis.
authors.affiliation: The Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK. jorgerf@icr.ac.uk
authors.forename: Jorge S
authors.initials: JS
authors.lastname: Reis-Filho
authors.forename: Dawn
authors.initials: D
authors.lastname: Steele
authors.forename: Silvana
authors.initials: S
authors.lastname: Di Palma
authors.forename: Robin L
authors.initials: RL
authors.lastname: Jones
authors.forename: Kay
authors.initials: K
authors.lastname: Savage
authors.forename: Michelle
authors.initials: M
authors.lastname: James
authors.forename: Fernanda
authors.initials: F
authors.lastname: Milanezi
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Schmitt
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D001940:Breast / Q000737:chemistry / Q000473:pathology*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D018226:Fibroadenoma / Q000378:metabolism / Q000473:pathology; D005348:Fibrocystic Breast Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053547:Keratin-14; D053555:Keratin-5; D053553:Keratin-6; D007633:Keratins / Q000032:analysis; D009208:Myoepithelioma / Q000378:metabolism / Q000473:pathology; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis*; D017475:Receptors, Nerve Growth Factor; D011980:Receptors, Progesterone / Q000032:analysis; D016019:Survival Analysis
chemical_list: C507540:KRT14 protein, human; C503940:KRT5 protein, human; C507569:KRT6A protein, human; C507570:KRT6B protein, human; C507571:KRT6C protein, human; D053547:Keratin-14; D053555:Keratin-5; D053553:Keratin-6; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; D011980:Receptors, Progesterone; D007633:Keratins