Heterozygous Men1+/T knockout mice do not develop bronchopulmonary neuroendocrine hyperplasia or neoplasia but bronchial adenocarcinoma

Abstract

Abstract Introduction: Bronchopulmonary Neuroendocrine Neoplasia (NEN) occur in 2-7% of patients with multiple endocrine neoplasia type 1 (MEN1). Precursor lesions could be recognized for MEN1 related pancreatic, duodenal, and gastric NEN. Aim of the current study of a Men1 mouse model was to define precursor lesions of bronchopulmonary NEN and potential prophylactic antitumor effects of somatostatin analogues in a transgenic Men1 mouse model. Methods: 15 mice, germline heterozygous for Men1 (+/T), were treated with subcutaneous injections of lanreotide autogel (Somatuline Autogel®, IPSEN Pharma) and 15 mice were treated with subcutaneous injections of physiologic sodium chloride as control group. Five mice each were euthanized after 12, 15, and 18 months, respectively. The complete lungs were resected and morphologically evaluated after HE staining and immunohistochemistry for synaptophysin and chromogranin A. Results: In the lungs of the 30 evaluated mice, treated or placebo treated, no bronchopulmonary neuroendocrine cell hyperplasia nor neuroendocrine neoplasia could be detected by histopathology. However, 2 (13%) of 15 untreated mice and one (7%) of 15 lanreotide treated mice developed pulmonary adenocarcinoma. Conclusion: Heterozygous Men1 (+/T) knockout mice do not develop bronchopulmonary NEN or precursor lesions, but pulmonary adenocarcinoma. This surprising result needs to be investigated in more detail.