Steroidogenesis in human adrenocortical carcinoma: Biochemical activities, immunohistochemistry, and in situ hybridization of steroidogenic enzymes and histopathologic study in nine cases

Hironobu Sasano, Takashi Suzuki, Hiroshi Nagura, Tetsuo Nishikawa

研究成果: Article査読

55 被引用数 (Scopus)

抄録

To obtain a better understanding of steroid metabolism associated with adrenocortical malignancy we studied steroidogenesis in nine cases of adrenocortical carcinoma (six with Cushing's syndrome, two without clinically significant adrenocortical hormonal abnormalities, and one with primary aldosteronism) by analyzing biochemical enzyme activities (21-hydroxylase and 11β-hydroxylase) and by immunohistochemistry and in situ hybridization of steroidogenic enzymes in carcinoma tissues. 21-Hydroxylase activity was markedly low but 11β-hydroxylase activity was only moderately decreased compared with normal adrenal activity. Immunohistochemical study of steroidogenic enzymes revealed that six of the nine cases expressed all the enzymes required for cortisol or aldosterone biosynthesis. Immunoreactivity of these enzymes was predominantly observed in small carcinoma cells with compact and/or clear cytoplasm and minimum morphologic nuclear atypia. In those cases with positive steroidogenic enzymes immunohistochemical examination of serial tissue sections revealed that a number of carcinoma cells did not express all the enzymes required for the synthesis of biologically active steroids. This may account for an increased level of precursor steroid secretion associated with adrenocortical malignancy. In situ hybridization of cytochrome 17α-hydroxylase demonstrated that carcinoma cells with positive hybridization signals generally were positive for immunoreactivity, but a discrepancy between mRNA and protein expression was occasionally observed. Although the conclusions derived from our current study are limited by the small number of cases, ineffective corticosteroidogenesis, characteristic of steroid metabolism in human adrenocortical carcinoma, was considered to be due to disorganized expression of steroidogenic enzymes in individual carcinoma cells.

本文言語English
ページ(範囲)397-404
ページ数8
ジャーナルHuman Pathology
24
4
DOI
出版ステータスPublished - 1993 4

ASJC Scopus subject areas

  • 病理学および法医学

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