Progression of eIF4E gene amplification and overexpression in benign and malignant tumors of the head and neck

BACKGROUND The overexpression of eukaryotic initiation factor 4E (eIF4E) results in the up‐regulation of gene products of mRNAs with long 5′ untranslated regions (5′ UTRs). The degree of gene amplification increases from the tumor free zone to the tumor core. This led the authors to hypothesize that 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 number and level of eIF4E protein expression. RESULTS There was no detectable eIF4E gene amplification and oncoprotein overexpression in benign tissue from noncancer patients (1.1 ± 0.5 gene copy number [mean ± standard deviation] and 0.9 ± 0.5‐fold protein elevation, 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 detectable eIF4E gene amplification and protein overexpression. Furthermore, the mean degree of eIF4E gene amplification and overexpression was found to increase 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 and 15.5 ± 9.3) were compared. CONCLUSIONS Progressive eIF4E gene amplification and overexpression were detected when normal tissues, benign tumors, and HNCA were compared. The degree of gene amplification and overexpression is variable within each tissue category. However, progression to malignant phenotype appears to be associated with an increasing degree of eIF4E gene amplification and overexpression. Cancer 2000;88:2803–10. © 2000 American Cancer Society. Eukaryotic initiation factor 4E (eIF4E) plays a critical role in selecting mRNAs for protein synthesis and its overexpression impacts on the up‐regulation of a number of known oncoproteins. When benign tissues, benign tumors, and invasive carcinoma of the head and neck regions were compared, there was progression of the degree of eIF4E gene amplification and overexpression.