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

To determine the relationship between p16(MTS1/CDK41) expression, gene inac tivation and 9p21 loss of heterozygosity (LOH) in the development of laryng eal carcinomas, we have examined p16(MTS1/CDK41) protein and mRNA expressio n 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(MTS 1/CDK41) protein expression (similar to normal samples), 7 carcinomas(19%) expressed higher levels, and no protein expression was seen in 14 tumors (3 9%). No gene alterations were detected in I I of the 15 tumors (73%) with p rotein 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). mR NA analysis showed p16(MTS1/CDK41)-gene expression in 12 of 17 carcinomas e xamined. 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 carcinoma s commonly associated with gene alterations and 9p21 LOH. The relative numb er of discrepancies between protein and mRNA expression and the presence of genetic alterations indicate that a comprehensive study of the gene includ ing all these parameters may be necessary to assess the role of this gene i n the pathogenesis of such tumors. (C) 1999 Wiley-Liss, Inc.