COMPARATIVE STUDY
JOURNAL ARTICLE

Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours

Grete Lottrup, John E Nielsen, Niels E Skakkebæk, Anders Juul, Ewa Rajpert-De Meyts
European Journal of Endocrinology 2015, 172 (4): 491-9
25609776

OBJECTIVE: Testicular adrenal rest tumours (TARTs) are a common finding in patients with congenital adrenal hyperplasia (CAH). These tumours constitute a diagnostic and management conundrum and may lead to infertility. TART cells share many functional and morphological similarities with Leydig cells (LCs), and masses consisting of such cells are occasionally misclassified as malignant testicular tumours, which may lead to erroneous orchiectomy in these patients.

DESIGN: In this study, we aimed to investigate the potential of LC developmental markers and adrenal steroidogenic markers in the differential diagnosis of TARTs and malignant LC tumours (LCTs).

METHODS: We investigated mRNA and protein expression of testicular steroidogenic enzymes; CYP11A1 and HSD3B1/2, markers of adrenal steroidogenesis; CYP11B1, CYP21A2 and ACTH receptor/melanocortin 2 receptor (MC2R), and markers of LC maturation; and delta-like 1 homolog (DLK1) and insulin-like 3 (INSL3) in testicular biopsies with TART, orchiectomy specimens with LCTs and samples from human fetal adrenals.

RESULTS: Expression of testicular steroidogenic enzymes was observed in all specimens. All investigated adrenal steroidogenic markers were expressed in TART, and weak reactions for CYP11B1 and MC2R were observed at the protein level in LTCs. TART and fetal adrenals had identical expression profiles. DLK1 was highly expressed and INSL3 not detectable in TART, whereas INSL3 was highly expressed in LCTs.

CONCLUSIONS: The similar expression profiles in TART and fetal adrenals as well as the presence of classical markers of adrenal steroidogenesis lend support to the hypothesis that TART develops from a displaced adrenal cell type. Malignant LCTs seem to have lost DLK1 expression and do not resemble immature LCs. The different expression pattern of DLK1, INSL3 and most adrenocortical markers adds to the elucidation of the histogenesis of testicular interstitial tumours and may facilitate histopathological diagnosis.

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