Progression of elF4E gene amplification and overexpression in benign and malignant tumors of the head and neck

BACKGROUND. The overexpression of eukaryotic initiation factor 4E (eIF4E) r esults in the up-regulation of gene products of mRNAs with long 5' untransl ated regions (5' UTRs). The degree of gene amplification increases from the tumor free zone to the tumor core. This led the authors to hypothesize tha t the degree of eIF4E gene amplification and oncoprotein overexpression is progressive in the cells from normal head and neck tissue, to benign tumors , and eventually to invasive carcinomas (HNCA). METHODS. Using competitive polymerase chain reaction (PCR) and Western blot analysis, benign specimens from similar sites of 10 noncancer patients, 8 pleomorphic adenoma specimens, and 18 HNCA specimens were studied. DNA and protein extracts from each specimen were quantified for eIF4E gene copy num ber and level of eIF4E protein expression. RESULTS. There was no detectable eIF4E gene amplification and oncoprotein o verexpression in benign tissue from noncancer patients (1.1 +/- 0.5 gene co py number [mean +/- standard deviation] and 0.9 +/- 0.5-fold protein elevat ion, respectively). Four of the eight pleomorphic adenomas analyzed showed eIF4E gene amplification of at least twofold, but none demonstrated protein elevation of any significance. In contrast, all HNCA specimens had detecta ble eIF4E gene amplification and protein overexpression. Furthermore, the m ean degree of eIF4E gene amplification and overexpression was found to incr ease as cells from benign head and neck tissues (1.1 +/- 0.5 and 0.9 +/- 0. 5), benign tumors (2.2 +/- 1.3 and 1.02 +/- 0.19), and HNCA (4.3 +/- 1.2 an d 15.5 +/- 9.3) were compared. CONCLUSIONS. Progressive eIF4E gene amplification and overexpression were d etected when normal tissues, benign tumors, and HNCA were compared. The deg ree of gene amplification and overexpression is variable within each tissue category. However, progression to malignant phenotype appears to be associ ated with an increasing degree of eIF4E gene amplification and overexpressi on. (C) 2000 American Cancer Society.