HIGH-FREQUENCY OF SIMULTANEOUS LOSS OF P16 AND P16-BETA GENE-EXPRESSION IN SQUAMOUS-CELL CARCINOMA OF THE ESOPHAGUS BUT NOT IN ADENOCARCINOMA OF THE ESOPHAGUS OR STOMACH

Quantitative reverse transcription PCR (RT-PCR) was used to measure ge ne expressions (relative mRNA levels) of p16 and the alternate transcr ipt p16 beta in esophageal and gastric tumors, p16 gene expression was undetectable in 13 of 25 esophageal squamous cell carcinomas. In 11 o f these tumors, p16 beta was simultaneously missing whereas two of the p16-deficient tumors still expressed p16 beta. Among 34 esophageal ad enocarcinomas and 11 gastric adenocarcinomas, only one tumor lacked p1 6 expression and all tumors expressed p16 beta. p16 sequences were not detectable by PCR in genomic DNA from tumors lacking both p16 and p16 beta mRNA, suggesting that the simultaneous loss of both gene express ions resulted from homozygous genomic deletion of the p16 gene. Howeve r, DNA from tumors that lacked p16 mRNA but expressed p16 beta did con tain the p16 gene, consistent with loss of p16 expression in these tum ors by transcriptional suppression. No point mutations in p16 cDNA wer e detected among 12 that were sequenced, but one p16 cDNA from a squam ous cell carcinoma had a 19-base deletion, possibly indicating a splic e-site mutation. Among those tumors that expressed p16 mRNA, the gene expression values of both p16 and p16 beta varied over a wide range. I n some cases, p16 expression was detectable but low, suggesting that d own-regulation of p16 expression may be used in some cases to achieve the funtional equivalent of gene deletion or transcriptional silencing . These results demonstrate that p16 expression patterns differ based on tumor histology and origin. Homozygous deletion of p16 appears to b e common in esophageal squamous cell carcinomas but in adenocarcinomas , both gene deletion and transcriptional silencing of p16 were infrequ ent.