Novel and Classic Myoepithelial/Stem Cell Markers in Metaplastic Carcinomas of the Breast

Abstract

Metaplastic carcinomas of the breast (MCBs) are unusual neoplasms characterized by an admixture of glandular epithelial components, which frequently exhibit features of squamous differentiation, and mesenchymal malignant components. Regardless of the presence of myoepithelial features in MCB, no consensus concerning their putative histogenesis has yet been achieved. Recently, novel putative myoepithelial markers have been developed, including p63, maspin, and P-cadherin. We assessed the expression of these myoepithelial markers in MCBs and compared their expression with classic myoepithelial markers. Immunohistochemistry using the streptavidinbiotin-peroxidase complex technique with antibodies raised against p63, maspin, P-cadherin, actin (clones CGA7, 1A4 and HHF35), cytokeratin 14 (Ck14), and vimentin was performed on 16 MCBs (7 matrix-producing MCBs, 6 adenosquamous MCBs, and 3 MCBs with heterologous elements). In healthy breast lobules and ducts adjacent to the tumors, myoepithelial cells showed distinctive and consistent immunoreactivity for p63, maspin, P-cadherin, actin, S-100 protein, and Ck14. Matrix-producing MCBs were positive for maspin in all cases, for p63 in 4 of 7 cases, and for P-cadherin in 4 of 7 cases. Adenosquamous MCB showed immunoreactivity for p63, maspin, and P-cadherin in 5 of 6 cases. All novel myoepithelial markers and Ck14 decorated squamous cell islands. MCBs with heterologous elements were positive for p63 in 1 case, for maspin in all 3 cases, and for P-cadherin in 2 cases. All cases showed at least one of the novel myoepithelial markers. Eleven of 16 cases were positive for actin. Eleven of 14 cases reacted with Ck14, and all cases that stained for S-100 protein (9 of 9) and vimentin (13 of 13) were also positive. Based on our findings, the balance of probabilities favors that MCBs may have a basal or myoepithelial cell histogenesis and differentiation.

Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial–mesenchymal transition

“…Myoepithelial carcinoma or carcinoma with myoepithelial differentiation exhibits a partial or total spindle growth pattern (Rosai, 2004). MCB is suggested to have a myoepithelial origin and express myoepithelial markers (Reis-Filho et al, 2003). Interestingly, three of the MCB subclass-2-overexpressed genes, SPARC, TIMP3 and LUM, are differentially overexpressed in myoepithelium (Jones et al, 2004;Kusafuka et al, 2004), and this might, in part, account for the sarcomatous (spindle) growth pattern seen in MCB.…”

Sox2: a possible driver of the basal-like phenotype in sporadic breast cancer

“…However, with the more comprehensive characterisation of basallike breast carcinomas, it has become clear that tumours arising in BRCA1 germline mutation carriers and sporadic basal-like breast carcinomas have genotypic and phenotypic traits that are remarkably similar. 2,3,7,8,10,11,14,[16][17][18][19][20]22,23,27,28,[49][50][51][52][53][54][55][56][57][58] Comparative genomic hybridisation (CGH) analysis has demonstrated that 3q copy number gains were an independent predictor of poor prognosis in a cohort of 76 sporadic node-negative breast tumours 59 and that these gains are significantly more prevalent in tumours arising in BRCA1 mutation carriers. 42,43 In addition, gains of the telomeric region of 3q are seen in approximately 20% of basal-like cancers and 10% of luminal tumours.…”

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

“…33,36,37,[40][41][42][43][44] NGFR positivity was significantly higher in metaplastic breast carcinomas when compared to that of a population-based cohort of breast cancers.…”

“…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.…”