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Updated: May 5, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
MEN1 gene mutation and reduced expression are associated with poor prognosis in pulmonary carcinoids
Dorian R A Swarts1, Aldo Scarpa, Vincenzo Corbo
1Departments of Molecular Cell Biology (D.R.A.S., M.E.R.H., F.C.S.R.) and Pathology (E.-J.M.S., M.v.E.), GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, The Netherlands; Applied Research on Cancer-NET Research Centre and Department of Pathology and Diagnostics (A.S., V.C.), University and Hospital Trust of Verona, 37134 Verona, Italy; Laboratory of Bioinformatics and Computational Genomics (W.V.C.), Ghent University, Belgium; Department of Oncology (G.G., M.P., M.V.), Division of Pathology, University of Turin at San Luigi Hospital, Orbassano, Torino, Italy; and Department of Pathology (A.P.), University of Bern, Bern, Switzerland.
Context:
MEN1 gene alterations have been implicated in lung carcinoids, but their effect on gene expression and disease outcome is unknown.
Objective:
Our objective was to analyze MEN1 gene and expression anomalies in lung neuroendocrine neoplasms and their correlations with clinicopathologic data and disease outcome.
Design:
We examined 74 lung neuroendocrine neoplasms including 58 carcinoids and 16 high-grade neuroendocrine carcinomas (HGNECs) for MEN1 mutations (n = 70) and allelic losses (n = 69), promoter hypermethylation (n = 65), and mRNA (n = 74) expression. Results were correlated with disease outcome.
Results:
MEN1 mutations were found in 7 of 55 (13%) carcinoids and in 1 HGNEC, mostly associated with loss of the second allele. MEN1 decreased expression levels correlated with the presence of mutations (P = .0060) and was also lower in HGNECs than carcinoids (P = .0024). MEN1 methylation was not associated with mRNA expression levels. Patients with carcinoids harboring MEN1 mutation and loss had shorter overall survival (P = .039 and P = .035, respectively) and low MEN1 mRNA levels correlated with distant metastasis (P = .00010) and shorter survival (P = .0071). In multivariate analysis, stage and MEN1 allelic loss were independent predictors of prognosis.
Conclusion:
Thirteen percent of pulmonary carcinoids harbor MEN1 mutation associated with reduced mRNA expression and poor prognosis. Also in mutation-negative tumors, low MEN1 gene expression correlates with an adverse disease outcome. Hypermethylation was excluded as the underlying mechanism.
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