Decreased p16Ink4A levels are commonly observed in all PAs and inversely correlated with tumor size and recurrence; dependence on PA type has also been observed.[43,44] In the majority of PAs, changes in p16Ink4A expression are not associated with gene mutation or loss, suggesting that genetic transformation of p16Ink4A is not involved in PA development.[45] Simpson et al[46] demonstrated that the pRb/p16/cyclin D1/CDK4 pathway is frequently deregulated in PAs, facilitating tumor formation. This evidence concerns the gene CDKN2A and neoplasm.