Tumor Suppressor Gene P16 <sup> Ink4a </ Sup> In The Insulinoma Expression

The p^16INK4a is frequently altered by homozygous deletion, mutation, or methylation in many nonendocrine tumors and these alterations may be important of tumor growth, or aggressiveness. Whether this is true for neuroendocrine tumors such as insulinomas is unclear. To address this question we analyzed the 45 insuliomas for p^16INK4a gene expression , its correlationship with insulin expression both in tumors and in paratumor islets, their methylation states, and then co-analyzed the results with tumors' biological behaviors. 70.6% (24/34) of insulinomas had down-regulated p16 expression, while the frequency in normal tissue was 17.9% (4/28), P=0.0016.This indicates that p16 is significantly down-regulated in insulinomas. We used MSP to detect the methylation state of p16's promoter region. 42.8% (9/21) of tumors proved to be methylated, thus mythelation might play an important role in pathogenensis of insulinomas.Through immunoflurescence, we found that the mean integrated opitical density(IOD/N) of p16 and insulin in paratumor islets positively correlated(r=0.559, P=0.047), but results as for p16 and glucagon were not this case (for normal islets: r=0.579, P=0.133; for paratumor islets:r=0.395, P=0.203) , which suggests p16 might have some intimate relationship with insulin expression. However, the same result was not shown in 3 tumor tissues ( r=0.849, p=0.354)。We found that in malignant insulinoma cell line RIN-m, the mean integrated opitical density(IOD/N) of p16 and insulin was positively correlated (r=0.721, P=0.028).