To date, the AP-2 family of transcription factors comprises five members. Transcription factor AP-2beta (TFAP2B)/AP-2β was first described in 1995. Several studies indicate a critical role of AP-2β in the development of tissues and organs of ectodermal, neuroectodermal and also mesodermal origin. Germline mutation of TFAP2B is known to cause the Char syndrome, an autosomal dominant disorder characterized by facial dysmorphism, patent ductus arteriosus and anatomical abnormalities of the fifth digit. Furthermore, single-nucleotide polymorphisms in TFAP2B were linked to obesity and specific personality traits. In neoplasias, AP-2β was first described in alveolar rhabdomyosarcoma. Immunohistochemical staining of AP-2β is a recommended ancillary test for the histopathological diagnosis of this uncommon childhood malignancy. In neuroblastoma, AP-2β supports noradrenergic differentiation.Recently, the function of AP-2β in breast cancer (BC) has gained interest. AP-2β is associated with the lobular BC subtype. Moreover, AP-2β controls BC cell proliferation and has a prognostic impact in patients with BC. This review provides a comprehensive overview of the current knowledge about AP-2β and its function in organ development, differentiation and tumorigenesis.

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.