Mutations of p53 tumor suppressor gene are of no significance in malignantneuroendocrine tumors

Background: Carcinoid tumors are potentially metastasizing neoplasms. These tumors are remarkably varied in their biologic behavior and may be indolen t for years. Methods: Thirty human neuroendocrine tumors of the gastrointestinal tract ( 20), pancreas (6) and the lung (4) were studied for the frequency and progn ostic significance of p53 protein expression and p53 mutation. 16 tumors sh owed a malignant follow-up. Paraffin embedded tissues were screened by immu nohistochemical methods. A panel of three monoclonal antibodies (DO-7, Pab 1801 and a cocktail of both 1:1) were employed by using the avidin-biotin p eroxidase complex technique. Additionally, genomic DNA was studied for p53 mutations by single strand conformation polymorphism (SSCP) and direct sequ encing for exons 5 to 8. Results: None of the samples showed positive staining for p53 whereas the p ositive control (undifferentiated thyroid carcinoma) showed clear staining with each antibody. Th(:se results were confirmed by PCR-SSCP. None of the amplified sequences showed conformational changes. Conclusion: It seems that neuroendocrine neoplasms do not follow the pathwa y of cancerogenesis described for other tumors by expression of p53 tumor g ene. The present study suggests that p53 gene mutation may be relatively un important in the genesis of neuroendocrine tumors.