Steroidogenic Acute Regulatory Protein Overexpression Correlates with Protein Kinase A Activation in Adrenocortical AdenomaReport as inadecuate




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The association of pathological features of cortisol-producing adrenocortical adenomas ACAs with somatic driver mutations and their molecular classification remain unclear. In this study, we explored the association between steroidogenic acute regulatory protein StAR expression and the driver mutations activating cyclic adenosine monophosphate cAMP-protein kinase A PKA signaling to identify the pathological markers of ACAs. Immunohistochemical staining for StAR and mutations in the protein kinase cAMP-activated catalytic subunit alpha PRKACA, protein kinase cAMP-dependent type I regulatory subunit alpha PRKAR1A and guanine nucleotide binding protein, alpha stimulating GNAS genes were examined in 97 ACAs. The association of StAR expression with the clinical and mutational features of the ACAs was analyzed. ACAs with mutations in PRKACA, GNAS, and PRKAR1A showed strong immunopositive staining for StAR. The concordance between high StAR expression and mutations activating cAMP-PKA signaling in the ACAs was 99.0%. ACAs with high expression of StAR had significantly smaller tumor volume P < 0.001 and higher urinary cortisol per tumor volume P = 0.032 than those with low expression of StAR. Our findings suggest that immunohistochemical staining for StAR is a reliable pathological approach for the diagnosis and classification of ACAs with cAMP-PKA signaling-activating mutations.



Author: Weiwei Zhou , Luming Wu , Jing Xie, Tingwei Su, Lei Jiang, Yiran Jiang, Yanan Cao, Jianmin Liu, Guang Ning, Weiqing Wang

Source: http://plos.srce.hr/



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