Analysis of 10 Adrenocortical Carcinoma Patients in the Cohort of the Precision Medicine Platform MONDTI

Abstract

Objective: Adrenocortical carcinoma (ACC) is a rare disease with a dismal prognosis. We aimed to evaluate if a personalized medicine approach may be useful for matching patients with ACC to targeted therapies. Methods: This is an analysis of 10 molecularly profiled ACCs that were progressing under standard of care treatment. The profile consisted of a 50-gene next-generation sequencing panel, immunohistochemistry (IHC), and fluorescence in situ hybridization for several proteins or chromosomal aberrations. Results: In 6 (60%) tumor samples, no somatic mutation was detected, while in 3 (30%) tumors 1 mutation was detected and in 1 (10%) tumor 2 mutations were detected. These mutations were CTNNB1 (2 samples), TP53 (1 sample), RB1 (1 sample) and APC (1 sample). Expression of phospho-mTOR and of EGFR was commonly detected by IHC (87.5 and 62.5%). In 4 (50%) samples, IHC revealed a weak expression of progesterone receptor. Less frequent alterations were expression of PDGFR-α, c-KIT, and estrogen receptor, each in 1 case. Conclusions: Based on the molecular profile, no recommendation for targeted therapy was made by the multi-disciplinary team. Currently, ACC might not be suitable for a precision medicine approach according to our tests.

What Did We Learn from the Molecular Biology of Adrenal Cortical Neoplasia? From Histopathology to Translational Genomics

“…Moreover, in several other syndromic diseases in which ACC is an established feature (Lynch syndrome [165,166], familial adenomatous polyposis (FAP) [167], multiple endocrine neoplasia type 1 (MEN1) [168][169][170], and neurofibromatosis type 1 (NF1)) [171,172], the corresponding genetic aberrancy was also found as somatic mutations in sporadic ACCs (MSH2, APC, MEN1, and NF1, respectively) [164,173]. In all, among the top 20 mutated genes on the somatic level in ACC, five (25%) are ACC syndromic genes (TP53, MSH2, APC, MEN1, and NF1)-thereby truly manifesting their importance as contributors in the development of ACC (Table 1).…”

Management of adrenocortical carcinoma: are we making progress?

“…At our own center, in a preliminary series of 10 patients no relevant targets were detected by use of a broad NGS panel. 93 …”

“…At our own center, in a preliminary series of 10 patients no relevant targets were detected by use of a broad NGS panel. 93 Is there a role for image guided therapy and theranostics? Chemokine receptor expression has been suggested as a relevant target for diagnostic and therapeutic purpose in a variety of tumor entities and both CXCR4 and CXCR7 were detected at relevant levels in ACC patients with localized or advanced disease, potentially offering options for CXCR4-directed treatment.…”

Feasibility of personalized treatment concepts in gastrointestinal malignancies: Sub-group results of prospective clinical phase II trial EXACT

“…Fresh tumor material was investigated for possible druggable targets via next generation sequencing (NGS), IHC and cytogenetic analysis. Results of the MP were discussed by a MDT within the frame of a tumor board for treatment decision ( 14 ). Out of 114 screened patients for the original EXACT trial, 55 (48%) were eligible to start targeted treatment based upon the MP derived from real-time biopsy.…”

“…Tumor samples were analyzed via NGS, IHC and cytogenetic analysis using the MONDTI platform ( 14 ). Most frequent somatic mutations discovered were TP53 (29%), KRAS (24%), IDH1 (10%), PTEN (10%) and SMAD4 (10%) ( Figure 1 ).…”