Diagnostic utility of p75 neurotrophin receptor (p75NTR) as a marker of breast myoepithelial cells

Abstract

We evaluated the low affinity neurotrophin receptor (p75 NTR ) as a marker of breast myoepithelial cells. Immunohistochemical staining for p75 NTR was performed on paraffin sections of 122 malignant breast lesions, 28 benign lesions and the adjacent normal breast tissue. The staining pattern was compared to those of myosin heavy chain and p63. p75 NTR immunostain was consistently positive and compatible with p63 and myosin immunoreactivity in the myoepithelial cells of the normal mammary gland, benign breast lesions (six usual ductal hyperplasias, six specimens with sclerosing adenosis, eight intraductal papillomas, six fibroadenomas), and carcinoma in situ (18 ductal carcinomas in situ, two noninvasive papillary carcinomas, two lobular carcinomas in situ). The luminal cells were negative for p75 NTR , but rare positive cells were noticed in the solid areas of some of the usual ductal hyperplasias. Four of 64 invasive ductal carcinomas (6%) and all metaplastic carcinomas (n ¼ 3, 100%) showed a variable degree of p75 NTR positivity. No p75 NTR expression was found in the malignant cells in all in situ carcinomas, invasive lobular carcinomas (n ¼ 11), tubular carcinomas (n ¼ 10), invasive papillary carcinomas (n ¼ 6), mucinous carcinomas (n ¼ 4), and medullary carcinomas (n ¼ 2). No myosin imunoreactivity was seen in the luminal/tumor cells, but p63 pattern of staining in the luminal/tumor cells was quite similar to that of p75 NTR . Although significant p75 NTR immunoreactivity was noticed in the vessels, nerves, and stromal component of fibroadenomas, no difficulties in the evaluation of the immunostain of myoepithelial cells were encountered. Our study shows that p75 NTR is a useful marker for breast myoepithelial cells and can be used to rule out invasive disease as well as to evaluate difficult for diagnosis sclerosing lesions. Our data suggest a role of neurotrophins in the development of fibroepithelial breast tumors and some of the breast carcinomas. Modern Pathology (2005) 18, 1535-1541.

Profiling genomic copy number changes in retinoblastoma beyond loss of RB1

“…Our findings suggest that the increases in expression seen in these two cancers are largely not mediated by genomic copy number change. The NGFR gene shows both genomic gain and loss in breast cancer cell lines, consistent with reports of variable expression (Aragona et al, 2001;Sakamoto et al, 2001;Davidson et al, 2004;Popnikolov et al, 2005;Reis-Filho et al, 2006).…”

Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

“…CD271 has been described as a unique marker of melanoma stem cells in humans (24). However, its first description in breast attributed it as a marker of myoepithelial cells (16). More recent studies show that its overexpression strongly increases resistance to anti-tumoral TRAIL treatment (25).…”

“…MM was detected by the M18 antibody, which recognizes branched glycans (15), whereas CD271/p75 NTR was detected by the ME20.4 antibody (16). We show that frankly differentiated luminal-like cells without acquiring appreciable basallike traits can be aggressive and invasive when serially transplanted into NOD SCID gamma (NSG) mice or tested for invasiveness in Boyden chambers.…”

Nerve growth factor receptor (NGFR): a potential marker for specific molecular subtypes of breast cancer

“…In the breast, NGFR expression was found in myoepithelial cells in normal breast tissue as well as benign and preinvasive breast lesions 12 13. Provisional data suggested that NGFR identified a subgroup of basal-like breast cancers (BLBC) with good prognosis 13.…”