Taking Advantage of Basic Research: p63 Is a Reliable Myoepithelial and Stem Cell Marker

Abstract

p63 is a recently characterized p53-homolog that is consistently expressed by basal/somatic stem cells of stratified epithelia, myoepithelial cells of the breast and salivary glands, and proliferative compartment of gastric mucosa. p63 is located on the long arm of chromosome 3 (3q27) and it encodes six isoforms, three transactivating (TA) and three DeltaN-isoforms. While the first three isoforms may act as tumor suppressor genes, the DeltaN-isoforms may inhibit the p53/TA-p63-driven cell cycle arrest and apoptosis. Recently, the putative applications of p63 in the identification of myoepithelial cells of the breast and basal cells of the prostate acini have been evaluated; however, no critical systematic analysis of its role in surgical pathology practice have hitherto been reported. We review the putative roles of p63 in surgical pathology practice and provide guidelines for future directions on p63 translational research.

Distribution and significance of nerve growth factor receptor (NGFR/p75NTR) in normal, benign and malignant breast tissue

“…However, NGFR expression in myofibroblasts was never as strong as that seen in myoepithelial cells and not as diffuse as that observed with a-smooth muscle actin. 19,21 In the stromal compartment of normal breast and benign and malignant breast lesions, the distribution of NGFR is strikingly similar to that described for CD34. 39,45,46 In fact, NGFR was consistently expressed by intralobular (myo)fibroblasts, stromal cells of benign biphasic neoplasms and in pseudoangiomatous stromal hyperplasias, but largely negative in the stromal compartment of invasive tumours.…”

“…19,37,49 On the other hand, some malignant tumours may harbour abortive myoepithelial differentiation, displaying poorly developed smooth muscle apparatus and frequently lacking expression of smooth muscle markers. 50 Therefore, based on our results, we advocate NGFR as an adjunct myoepithelial marker that in conjunction with other antibodies may be utilised to identify myoepithelial differentiation in breast neoplasms.…”

“…p63 was chosen because it is consistently expressed in nuclear compartment of normal myoepithelial cells, 19,37 allowing an objective assessment of NGFR (membrane) and p63 (nucleus) coexpression. Briefly, slides were subjected to high-temperature antigen retrieval (18 min of microwaving in citrate buffer (pH 6.0)), allowed to cool for 20 min at room temperature and then incubated in Envision þ peroxidase blocking solution (Dakocytomation) for 5 min, rinsed in water and transferred to TBS.…”

“…For example, distinguishing ductal carcinoma in situ (DCIS) vs invasive ductal carcinoma, radial scar vs infiltrating tubular carcinoma, cancerisation of sclerosing adenosis by DCIS mimicking invasive breast carcinoma, adenoid cystic carcinoma vs collagenous spherulosis or cribriform DCIS, papillary carcinoma vs papilloma, and nipple adenoma vs invasive ductal carcinoma. [18][19][20][21] In recent years, several myoepithelial markers have been described, most of them either related to the basal nature of myoepithelial cells or to the smooth muscle apparatus of these cells. [18][19][20][21][22] However, the development of novel myoepithelial markers is not only important for diagnostic purposes but also for prognostication.…”

“…[18][19][20][21] In recent years, several myoepithelial markers have been described, most of them either related to the basal nature of myoepithelial cells or to the smooth muscle apparatus of these cells. [18][19][20][21][22] However, the development of novel myoepithelial markers is not only important for diagnostic purposes but also for prognostication. There are several lines of evidence to suggest that highgrade breast carcinomas expressing basal/myoepithelial markers have distinct pathological features, expression profiles and, most importantly, clinical behaviour when compared to high-grade breast carcinomas devoid of basal-like differentiation.…”