Neuroendocrine breast carcinomas of aged women may express apocrine differentiation markers

Neuroendocrine (NE) carcinomas of the breast are a rare entity that diffusely expresses NE markers. We here demonstrate that NE breast carcinomas in elderly women can also express apocrine immuno-phenotype, and analyze the histological and clinical aspects of such differentiation. A selected series of 50 NE tumors (positive for NE markers in >50% of the cells) was tested for the immunocytochemical expression of gross cystic disease fluid protein-15 (GCDFP-15). About 50% of moderately (G2) and well-differentiated (G1) NE breast carcinomas coexpressed the apocrine marker. In these cases specific mRNA for GCDFP-15 (PIP) and for chromogranin A was demonstrated using in situ hybridization (ISH). Carcinomas of the alveolar subtype (G2) and poorly differentiated carcinomas (G3) were pure NE carcinomas, devoid of apocrine differentiation. The steroid receptor status of these lesions was evaluated to test a possible involvement of androgen receptors (AR) in apocrine differentiation. The level of AR and the mean age of patients at diagnosis were significantly higher in apocrine than in nonapocrine differentiated tumors. The histological grade and the expression of estrogen receptor significantly influenced the prognosis of these NE carcinomas, either pure or NE-apocrine differentiated. In conclusion, NE breast carcinomas may exhibit divergent apocrine differentiation that might be regulated by the activation of AR in elderly patients. In addition, the possibility to use Chs or GCDFP-15 serum values in the follow up of these patients, as demonstrated in two cases of the present series, can justify the immunophenotyping of the tumors.