Novel Germ Line Mutation p53-P177R in Adult Adrenocortical Carcinoma Producing Neuron-specific Enolase as a Possible Marker

Abstract

Adrenocortical cancer (ACC) is a rare and aggressive endocrine tumor. The patient presented with a large retroperitoneum tumor and lung metastases. Removal of the adrenocortical tumor with part of the transverse colon and tail of the pancreas, spleen and kidney was successfully performed following chemotherapy. Levels of serum neuron-specific enolase (NSE) were found to be markedly high before surgery and may be clinically useful markers for monitoring tumor status during management. Immunohistochemical studies showed that the cancer cells were positive for NSE and overexpression of p53. We identified a novel germ line variant of the 177 mutant (Pro to Arg; P177R) of p53 by genomic sequencing. The genetic and biochemical data presented in this case confirm the importance of screening for p53 status in ACC with inherited cancer syndrome.

The Role of Biomarkers in Adrenocortical Carcinoma: A Review of Current Evidence and Future Perspectives

“…Generally, NSE is a highly specific marker for neurons and peripheral neuroendocrine cells and it is an index of neural maturation. In this report, immunohistochemical analysis has shown positivity for NSE and overexpression of p53 [134]. Finally, a novel germ line variant of the 177 mutant (Pro to Arg; P177R) of p53 by genomic sequencing was then identified [134].…”

“…Low SGK1 expression was connected to ACTH-independent cortisol secretion in adrenocortical tumors and might be considered as a new prognostic factor in adrenocortical carcinoma [133]. In a report of a patient case with ACC, a high level of serum neuron-specific enolase (NSE) was noticed before operation and was considered as useful marker for monitoring tumor status during management [134]. Generally, NSE is a highly specific marker for neurons and peripheral neuroendocrine cells and it is an index of neural maturation.…”

Isolation, characterization and functional analysis of full length p53 cDNA from Bubalus bubalis

“…DNA binding domain was isolated. Out of three point mutations P169H, F205L and I225T; P169 is homologous to P177 in a mutant of human p53 reported in germline adenocarcinoma (Ide et al, 2010). When transfected, mutant-Bp53 accumulated in both H1299 and buffalo mammary cells (Fig.…”

TP53Germline Mutations in Adult Patients with Adrenocortical Carcinoma

“…According to these criteria, a subject with ACC is likely to carry a germline TP53 mutation regardless of age at diagnosis or family history (13). However, TP53 germline mutations in adult ACC patients have so far been described only in small series (14,15), as single case reports (16), or in the context of families connected to LFS (17)(18)(19). The largest series in adult patients with ACC came again from southern Brazil, including 37 patients from the above-mentioned area of high ACC prevalence due the R337H founder mutation (20).…”