Endocrine Abstracts

Background: Adrenocortical tumors consist of benign adenomas (ACA) and highly malignant carcinomas (ACC). Dysregulation of the Notch signalling pathway is implicated in several cancers with oncogenic or tumor suppressor functions. JAG1 is a Notch1 ligand of the Jagged family and a common target gene for Notch and Wnt/β catenin pathways. It has been reported that upregulated expression of JAG1 enhances cell proliferation in ACC.

Material and methods: The mRNA expression of NOTCH1, JAG1, and some specific target genes (HES1, HES5, and HEY2) was evaluated in 49 fresh frozen samples (13 normal adrenal glands, 17 ACA and 19 ACC) by quantitative real-time PCR. Immunohistochemistry was performed in 202 tissues on paraffin slides (six normal adrenal glands, 25 ACA, 171 ACC) for the evaluation of JAG1 protein expression.

Results: The mRNA expression of NOTCH1, HES1 and HES5 was similar in the three groups. On the other hand, HEY2 and JAG levels were higher in ACC than in ACA (both P<0.005). The JAG1 protein was expressed (H-score from 1 to 3) in significantly more ACC than ACA (73 vs 39%, P<0.005). Interestingly, high JAG1 protein expression was also associated with a better prognosis in ACC patients. This was true both in terms of overall survival (n=126, median 110 vs 30 months, HR=1.9, 95% CI=1.2–3.1, P=0.0068) and disease-free survival (n=45, median 49 vs 18 months, HR=2.0, 95% CI=0.9–4.2, P=0.07).

Conclusion: Notch1 signaling pathway activation might be involved in adrenocortical tumor progression and need to be further investigated. However, high JAG1 expression seems to play rather a protective role in established ACC and its expression might represent a new positive prognostic factor.