Co-expression of transcription factor AP-2beta (TFAP2B) and GATA3 in human mammary epithelial cells with intense, apicobasal immunoreactivity for CK8/18

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.

Optimized Modeling of Metastatic Triple-Negative Invasive Lobular Breast Carcinoma

“…The epithelial markers CK8/18 and CK7 were expressed ( Figure 4 J–K), as was GATA3, which has been associated to the luminal BC subtype ( Figure 4 H). Notably, the expression of transcription factor TFAP2B ( Figure 4 I), a luminal mammary epithelial differentiation marker and a well-established marker for lobular carcinoma that controls tumor cell proliferation in this slow-growing BC subtype, was detected [ 24 , 25 ].…”

“…The epithelial markers CK8/18 and CK7 were expressed (Figure 4J-K), as was GATA3, which has been associated to the luminal BC subtype (Figure 4H). Notably, the expression of transcription factor TFAP2B (Figure 4I), a luminal mammary epithelial differentiation marker and a well-established marker for lobular carcinoma that controls tumor cell proliferation in this slow-growing BC subtype, was detected [24,25]. In the invasive components, we found a comparable expression in all markers tested, except for a slightly higher proliferative index as measured by Ki67 (30-35%) (Figure 5C) and a slightly lower HER2 expression (IHC score 1+ to 2+) (Figure 5L).…”