Molecular analysis and literature-based hypothesis of an immunonegative prostate small cell carcinoma causing ectopic ACTH syndrome

Endocrine journal

Maki Takeuchi¹  Junichiro Sato²  Mariko Tanaka³  Katsunori Manaka⁴ 

[1] Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo, Japan;Department of Pathology, The University of Tokyo, Tokyo, Japan;Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Japan;Department of Urology, The University of Tokyo, Tokyo, Japan

关键词: Ectopic ACTH syndrome;    Prostate small cell carcinoma;    Immunostaining;    Proopiomelanocortin (POMC);    De-differentiation;   

DOI  :  10.1507/endocrj.EJ18-0563

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

Ectopic ACTH syndrome (EAS) due to a prostate small cell carcinoma (SCC) is very rare with only 26 cases reported to date and has a poor prognosis. We here describe another case of this disorder that was clinically typical based on prior reports as it showed hypercortisolemia and severe hypokalemia with multiple metastasis. However, our current case of prostate SCC causing EAS is the first to display negative immunostaining for ACTH despite detectable POMC mRNA expression in the primary lesion. ACTH immunonegativity is thought to be associated with a more aggressive disease course and a poorer prognosis although there are few studies of the underlying mechanisms. We explored two possibilities for this finding in our current patient: aberrant POMC processing prevented immunodetection with an anti-ACTH antibody; and the ACTH content per cell was below the threshold for immunodetection due to its rapid secretion or low synthesis. The aberrant processing theory was thought to be less likely because of immunonegative findings even using anti-POMC/ACTH antibodies. As the plasma ACTH levels in our patient were comparable with those reported for previous immunopositive prostate EAS cases, we speculated that the depletion of ACTH may be caused not only by rapid secretion but also by low production levels as a sign of de-differentiation. De-differentiation may therefore explain the mechanism underlying the negative correlation between immunoreactivity for ACTH in EAS and disease aggressiveness. We believe that our present findings will be of use in future prospective studies aimed at confirming the mechanism of immunonegativity.

【 授权许可】

Unknown