I. MULTIPLE ENDOCRINE NEOPLASIA (MEN)
Multiple Endocrine Neoplasia (MEN) is a group of autosomal dominant hereditary cancer syndromes characterized by the development of tumors in multiple endocrine glands.
MEN syndromes are divided mainly into MEN type 1 and MEN type 2.
MEN TYPE 1 (Wermer Syndrome)
Genetic Basis
- Gene: MEN1
- Chromosome: 11q13
- Protein: Menin (tumor suppressor)
Normal Function of Menin
Menin regulates:
- cell cycle control,
- transcription,
- DNA repair.
Loss of menin leads to uncontrolled endocrine cell proliferation.
Pathogenesis of MEN1
- Germline mutation in one MEN1 allele.
- Second somatic hit in endocrine tissues.
- Loss of tumor suppressor function.
- Development of multiple endocrine tumors.
Clinical Features – “3 Ps”
- Parathyroid adenomas → hyperparathyroidism (most common)
- Pancreatic neuroendocrine tumors (gastrinoma, insulinoma)
- Pituitary adenomas (prolactinoma common)
MEN TYPE 2
Genetic Basis
- Gene: RET proto-oncogene
- Chromosome: 10q11
- Mutation type: activating (gain-of-function)
MEN2 Subtypes
Pathogenesis of MEN2
- Activating mutation of RET.
- Constitutive tyrosine kinase signaling.
- Continuous cell proliferation.
- Early tumor development, especially in thyroid C-cells.
Key Clinical Points
- Medullary thyroid carcinoma (MTC) is the hallmark.
- Prophylactic thyroidectomy is life-saving.
- Tumors arise from neural crest–derived cells.