Peritoneal Carcinosis in Apparently Benign Cortisol Producing Adrenal Adenoma≥5 cm in Diameter: The Need of Regular Postoperative Surveillance

Brauckhoff, Michael; Je, Varhaug; Hauptmann, S; Akslen, LA; Pn, Thanh; Viste, Asgaut; Heie, Anette; Dralle, Henning

doi:10.1055/s-0032-1321807

Cited by 4 publications

(1 citation statement)

References 13 publications

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“…These tumors may come to early attention due to clinical signs and symptoms of cortisol excess. Interestingly, some adrenal cortisol-producing tumors initially classified as benign have recurred with invasive or metastatic disease 55 . Similarly, other studies in mice and humans have also suggested a multistep model of progression from adrenal hyperplasia to adenoma and carcinoma 56–58 .…”

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confidence: 99%

Recurrent activating mutation in PRKACA in cortisol-producing adrenal tumors

et al. 2014

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Adrenal tumors autonomously producing cortisol cause Cushing syndrome1–4. Exome sequencing of 25 tumor-normal pairs revealed two groups. Eight tumors (including 3 carcinomas) had many somatic copy number variants (CNV+) with frequent deletion of CDC42 and CDKN2A, amplification of 5q31.2, and protein-altering mutations in TP53 and RB1. Seventeen (all adenomas) had no CNVs (CNV-), TP53 or RB1 mutations. Six of these had known gain of function mutations in CTNNB15,6 (beta-catenin) or GNAS7,8 (Gαs), Six others had somatic p.Leu206Arg mutations in PRKACA (protein kinase A (PKA) catalytic subunit). Further sequencing identified this mutation in 13 of 63 tumors (35% of adenomas with overt CS). PRKACA, GNAS and CTNNB1 mutations were mutually exclusive. Leu206 directly interacts with PKA’s regulatory subunit, PRKAR1A9,10. PRKACAL206R loses PRKAR1A binding, increasing phosphorylation of downstream targets. PKA activity induces cortisol production and cell proliferation11–15, providing a mechanism for tumor development. These findings define distinct mechanisms underlying adrenal cortisol-producing tumors.

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confidence: 99%