ABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinicopathologic significance of P16 3D structure alterations in human esophageal squamous cell carcinoma(ESCC) so as to open a new approach for the research on clinical prevention and treatment of ESCC.</p><p><b>METHODS</b>All three techniques of polymerase chain reaction-single strand comformation polymorphism (PCR-SSCP), DNA sequencing and computerized three-dimensional protein-modeling were applied to analyze and determine the gene mutations and the computerized 3D changes of P16 protein molecule.</p><p><b>RESULTS</b>The p16 gene abnormality were detected from thirty-three cases of sixty-nine ESCC, among which twenty-six cases of ESCC showed the alterations of amino acid residues located within the P16 functional domains (classified as group M2), but other seven cases displayed the amino acid changes happened to beyond the domains and far from the p16-CDK4/6 binding site (defined as group M1). The statistical analysis revealed that the significant differences in lymph node metastasis, distance metastasis and stage of clinical were found between M2 and M1 groups (P<0.05). However no significant difference in sex, age, invasion depth of tumor was observed (P>0.05).</p><p><b>CONCLUSION</b>The mutations of p16 gene will alter the P16 protein structure. The four ankyrin repeats are the critical regions of P16 protein. The abnormalities in the ankyrin repeats will seriously alter the 3D structure and the activity of P16 protein, with resulting in lymph node metastasis, distance metastasis, and clinically advanced stage. The above results render an authentic criterion to the selection of the clinical cases with high risk of metastasis.</p>