Targeted Molecular Analysis in Adrenocortical Carcinomas: A Strategy Toward Improved Personalized Prognostication

Abstract

This study demonstrates that molecular profiling of FFPE tumor samples improves prognostication of ACC beyond clinical/histopathological parameters and identifies new potential drug targets. These findings pave the way to precision medicine in this rare disease.

Targeted Gene Expression Profile Reveals CDK4 as Therapeutic Target for Selected Patients With Adrenocortical Carcinoma

“…Adrenocortical carcinoma (ACC) is a rare and aggressive tumor with generally poor but heterogeneous prognosis, which can be assessed by initial tumor stage and histopathological parameters like Ki67 proliferation index (1,2). The presence of metastatic disease is associated with overall 5 year survival of <15% (1,3,4).…”

“…For ACC, biomarkers such as specific transcriptomic profiles, copy number alteration patterns and methylation in certain promoter regions have been identified by genome-wide studies to be associated with tumor aggressiveness and clinical outcome (12)(13)(14)(15). In addition, previous molecular screenings have provided some promising insights into pharmacological targets, such as proteins involved in the cell cycle or tyrosine kinase receptors (2,16,17). The efficacy of some of these potential targets have previously been investigated in small clinical studies, but patients were not pre-selected and results were largely negative (18)(19)(20)(21)(22)(23).…”

CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant

“…In particular, somatic variants in TP53 (16-20%) and CTNNB1 (about 15%) have been the most frequently reported in ACC [14,15]. Somatic variants in these two genes are reported as a poor prognostic factor [12,16,17,18]. However, how the somatic variant in TP53 or CTNNB1 affects clinical and pathological findings and leads to poor prognosis of ACC is not fully elucidated.…”

“…We selected candidate genes, in which somatic variants might be related to poor prognosis. Ten genes (APC, CCNE1, CDK4, CDKN2A, CTNNB1, MDM2, MEN1, RB1, TP53, and ZNRF3) involved in TP53-RB1 and Wnt pathways were selected because TP53 and CTNNB1 somatic variants have been reported as poor prognostic factors in ACC [12,16,17,18]. Somatic variants in these ten candidate genes were detailed in previous papers and were suitable for a comparative study between Japanese and other races.…”

Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma

“…While surgical resection remains the first option, nearly 50% of ACC patients who undergo initial complete resection develop recurrent or metastatic disease [3]. Tumor stage is determined according to the European Network for the Study of Adrenal Tumors' (ENSAT) classifi-cation of TNM stages [4], resection (R) status [5,6], Ki67 index [7], and a set of newfound biomarkers [8] that represent the known prognostic factors.…”