Pelte Marie-Françoise, Schwaller Jurg, Cerrato Christelle, Meier Christoph A
Department of Clinical Pathology, Department of Medicine, Geneva University Hospital, Geneva, Switzerland.
Breast J. 2004 Jul-Aug;10(4):350-4. doi: 10.1111/j.1075-122X.2004.21467.x.
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.
继发于异位促肾上腺皮质激素（ACTH）分泌的库欣综合征在乳腺癌中很少见，此前仅发表过4例。我们在此报告一例50岁女性，她有弥漫性骨痛病史，伴有多发肝、肺和骨转移。粗针活检标本显示右乳浸润性导管癌。患者随后发生了ACTH依赖性副肿瘤性库欣综合征，尽管接受了治疗，但仍死于心律失常和心力衰竭。尸检时，免疫组化染色显示乳腺肿瘤和肺转移灶中嗜铬粒蛋白A和ACTH呈阳性。通过逆转录聚合酶链反应（RT-PCR）在肿瘤细胞中检测到了阿黑皮素原（POMC）基因的mRNA表达。这是首例继发于异位ACTH分泌的库欣综合征，其中免疫组化显示ACTH存在，RT-PCR显示POMC基因在伴有转移的乳腺癌中均有表达。本文介绍了该病例的临床病史、病理发现以及分子分析的方法和结果。该病例说明了一例具有神经内分泌（NE）分化的乳腺癌中的异位ACTH综合征。这种NE表型与肿瘤细胞合成ACTH直接相关。应记住，异位ACTH综合征不仅可能由小细胞癌或内分泌肿瘤引起，也可能由乳腺癌引起。对于这种特殊类型的乳腺癌，NE特征与预后因素或患者结局之间尚未建立联系。在具有NE特征的乳腺癌中检测到mRNA POMC表明与NE分化相关的POMC基因存在抑制和/或激活。
