Abstract

AP-2β is a new mammary epithelial differentiation marker and its expression is preferentially retained and enhanced in lobular carcinoma in situ and invasive lobular breast cancer. In normal breast epithelium AP-2β is expressed in a scattered subpopulation of luminal cells. So far, these cells have not been further characterized. Co-expression of AP-2β protein and luminal epithelium markers (GATA3, CK8/18), hormone receptors [estrogen receptor (ER), androgen receptor (AR)] and candidate stem cells markers (CK5/14, CD44) were assessed by double-immunofluorescence staining in normal mammary gland epithelium. The subpopulation of AP-2β-positive mammary epithelial cells showed an almost complete, superimposable co-expression with GATA3 and a peculiar intense, ring-like appearing immunoreactivity for CK8/18. Confocal immunofluorescence microscopy revealed an apicobasal staining for CK8/18 in AP-2β-positive cells, which was not seen in in AP-2β-negative cells. Furthermore, AP-2β-positive displayed a partial co-expression with ER and AR, but lacked expression of candidate stem cell markers CK5/14 and CD44. In summary, AP-2β is a new luminal mammary epithelial differentiation marker, which is expressed in the GATA3-positive subpopulation of luminal epithelial cells. These AP-2β-positive/GATA3-positive cells also show a peculiar CK8/18-expression which may indicate a previously unknown functionally specialized mammary epithelial cell population.

Highlights

  • TFAP2B/AP-2β is a member of the activator protein-2 (AP2) family of transcription factors, which comprises five members (AP-2α, -2β, -2γ, -2δ, -2ε), encoded by separate genes (TFAP2A, TFAP2B, TFAP2C, TFAP2D, TFAP2E) (Pellikainen and Kosma 2007)

  • That AP-2β is expressed in approximately 30% of luminal breast epithelial cells (Raap et al 2018)

  • Doubleimmunofluorescence staining with CK8/18 showed that AP-2β expression was restricted to cells expressing these luminal epithelial cytokeratins

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Summary

Introduction

TFAP2B/AP-2β is a member of the activator protein-2 (AP2) family of transcription factors, which comprises five members (AP-2α, -2β, -2γ, -2δ, -2ε), encoded by separate genes (TFAP2A, TFAP2B, TFAP2C, TFAP2D, TFAP2E) (Pellikainen and Kosma 2007). TFAP2B has been implicated in neoplastic diseases (Ebauer et al 2007; Grass et al 2009; Ikram et al 2016; Li et al 2018; Wachtel et al 2006). Contrary to the results in aRMS, AP-2β seems to be a favorable prognostic marker in carcinomas such as endometrial cancer (Wu and Zhang 2018), cervical cancer (Wang et al 2017), renal cell cancer (Oya et al 2004), neuroblastoma (Ikram et al 2016; Thorell et al 2009) and breast cancer (BC) (Raap et al 2018; Yoldi et al 2016)

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