Search Results
You are looking at 1 - 1 of 1 items for
- Author: Michaela Bekteshi x
- Refine by access: All content x
Search for other papers by Cristina L Ronchi in
Google Scholar
PubMed
Search for other papers by Silviu Sbiera in
Google Scholar
PubMed
Search for other papers by Barbara Altieri in
Google Scholar
PubMed
Search for other papers by Sonja Steinhauer in
Google Scholar
PubMed
Endocrine and Diabetes Unit, Central Laboratory, Institute of Pathology, Comprehensive Cancer Center Mainfranken, Department of Internal Medicine I, University Hospital, University of Wuerzburg, Oberrduerrbacher-Strasse 6, 97080 Wuerzburg, Germany
Search for other papers by Vanessa Wild in
Google Scholar
PubMed
Search for other papers by Michaela Bekteshi in
Google Scholar
PubMed
Search for other papers by Matthias Kroiss in
Google Scholar
PubMed
Search for other papers by Martin Fassnacht in
Google Scholar
PubMed
Search for other papers by Bruno Allolio in
Google Scholar
PubMed
Previous SNP array analyses have revealed genomic alterations of the Notch pathway as being the most frequent abnormality in adrenocortical tumors (ACTs). The aim of the present study was to evaluate the expression of components of Notch signaling in ACTs and to correlate them with clinical outcome. The mRNA expression of JAG1, NOTCH1, and selected target genes of NOTCH1 (HES1, HES5, and HEY2) was evaluated in 80 fresh frozen samples (28 normal adrenal glands (NAGs), 24 adenomas (ACAs), and 28 carcinomas (ACCs)) by quantitative RT-PCR. Immunohistochemistry was performed in 221 tissues on paraffin slides (16 NAGs, 27 ACAs, and 178 ACCs) for JAG1, activated NOTCH1 (aNOTCH1), and HEY2. An independent ACC validation cohort (n=77) was then also investigated. HEY2 mRNA expression was higher in ACCs than it was in ACAs (P<0.05). The protein expression of all of the factors was high (H-score 2–3) in a larger proportion of ACCs as compared to ACAs and NAGs (JAG1 in 27, 15, and 10%; aNOTCH1 in 13, 8, and 0%; HEY2 in 66, 61, and 33% respectively, all P<0.001). High JAG1 expression was associated with earlier tumor stages and lower numbers of metastases in ACCs (both P=0.08) and favorably impacted overall and progression-free survival (PFS) (131 vs 30 months, hazard ratio (HR) 0.45, and 37 vs 9 months, HR 0.51, both P<0.005). This impact on overall survival (OS) was confirmed in the validation cohort. No such association was observed for aNOTCH1 or HEY2. In conclusion, different components of the Notch1 signaling pathway are overexpressed in ACCs, which suggests a role for the pathway in malignant transformation. However, JAG1 is overexpressed in a subgroup of ACCs with a better clinical outcome.
