Concordant loss of MTAP and p16/CDKN2A expression in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion.

摘要: The p16INK4A/CDKN2A (p16) gene on chromosome 9p21 is inactivated in >90% of invasive pancreatic cancers. In 40% cancers the p16 by homozygous deletion, an intragenic mutation coupled with loss second allele, and 10-15% hypermethylation promoter. Immunohistochemical labeling for product parallels status, but does not provide information mechanism inactivation. methylthioadenosine phosphorylase (MTAP) also resides 9p21, approximately 100 kb telomeric to gene. MTAP frequently contained within deletions, producing concordant both expression. Concordant protein expression can therefore be used as a surrogate marker deletion. Here we immunolabeled series intraepithelial neoplasia (PanIN) lesions various histologic grades products using high-throughput PanIN tissue microarray (TMA) format. We demonstrate 6/73 (8%) PanINs, including five high-grade one low-grade lesion. Immunolabeling provides tool evaluate tissues intact morphology deletions. genes demonstrates that deletions tumor suppressor occur noninvasive precursor lesions.