Disregulation of p16(MTS1/CDK4I) protein and mRNA expression is associated with gene alterations in squamous-cell carcinoma of the larynx

To determine the relationship between p16(MTS1/CDK41) expression, gene inactivation and 9p21 loss of heterozygosity (LOH) in the development of laryngeal carcinomas, we have examined p16(MTS1/CDK41) protein and mRNA expression in a series of 7 normal and 36 tumoral tissues, and the presence of gene alterations and 9p21 LOH. Fifteen tumors (42%) showed low levels of p16(MTS1/CDK41) protein expression (similar to normal samples), 7 carcinomas(19%) expressed higher levels, and no protein expression was seen in 14 tumors (39%). No gene alterations were detected in I I of the 15 tumors (73%) with protein levels similar to normal tissues. Most of the cases with absence of protein expression (86%) had gene alterations. Of the 7 tumors with protein over-expression, 4 showed frameshift or point mutations (2 cases each). mRNA analysis showed p16(MTS1/CDK41)-gene expression in 12 of 17 carcinomas examined. Gene alterations were detected in 9 of the 12 mRNA-positive tumors and in 2 of the 5 negative carcinomas. Concordant expression of p16 alpha and p16 beta transcripts was observed in all tumors. 9p21 LOH was detected in 23 carcinomas, 18 of which (78%) showed associated p16(MTS1/CDK41). gene alterations. These results indicate that disregulation of p16(MTS1/CDK41) protein and mRNA expression is a frequent phenomenon in laryngeal carcinomas commonly associated with gene alterations and 9p21 LOH. The relative number of discrepancies between protein and mRNA expression and the presence of genetic alterations indicate that a comprehensive study of the gene including all these parameters may be necessary to assess the role of this gene in the pathogenesis of such tumors. (C) 1999 Wiley-Liss, Inc.