Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion

Cushing's syndrome secondary to ectopic adrenocorticotropic hormone (ACTH) secretion is rarely observed in breast carcinoma and only four cases have been previously published. We report here the case of a 50-year-old woman who presented with a history of diffuse bone pain associated with multiple hepatic, pulmonary, and bone metastases. A core needle biopsy specimen revealed an invasive ductal carcinoma in the right breast. The patient subsequently developed an ACTH-dependent paraneoplastic Cushing's syndrome and she died of arrhythmia and heart failure, despite treatment. At autopsy, immunohistochemical staining showed chromogranin A and ACTH positivity in the breast tumor and a lung metastasis. The mRNA expression of the pro-opiomelanocortin (POMC) gene was detected in tumoral cells by reverse transcriptase polymerase chain reaction (RT-PCR). This is the first case of Cushing's syndrome secondary to ectopic ACTH secretion where the presence of ACTH by immunohistochemistry and the expression of the POMC gene by RT-PCR have both been demonstrated in a breast carcinoma with metastases. The clinical history and the pathologic findings are presented with the methods and results of the molecular analysis. This case illustrates an example of ectopic ACTH syndrome in a breast carcinoma with neuroendocrine (NE) differentiation. This NE phenotype is directly related to the synthesis of ACTH by the tumoral cells. It should be kept in mind that an ectopic ACTH syndrome may be produced not only by small cell carcinoma or endocrine tumors but also by breast cancer. No relationship has been established between NE features and prognostic factors or patient outcome for this peculiar type of breast carcinoma. The demonstration of mRNA POMC in breast carcinoma with NE features suggests a depression and/or an activation of the POMC gene linked to the NE differentiation.