HEAD AND NECK SQUAMOUS-CELL CARCINOMAS - CLINICAL RELEVANCE OF ONCOGENE AMPLIFICATIONS

Squamous cell carcinomas of the head and neck from 50 untreated patien ts were analyzed for rearranged or amplified proto-oncogenes by Southe rn blot hybridization. The bcl-1 and hst genes were coamplified 8- to 32-fold in 5 of 46 patients (11%) and the c-erb A1 and c-erb B2 genes 32-fold in 1 of 46 patients (2%). Eight to 16-fold amplification of c- myc was observed in 4 of 46 tumor samples (8%), while 4-fold amplifica tion of Ha-ras was found in 2 of 46 tumor samples (4%). There was one patient with a 64-fold c-erb B2 amplification without accompanying c-e rb A1 amplification. RNA - expression analysis using Northern blot and poly-A-+ RNA techniques did not reveal any changes in the RNA express ion of c-erb Al while c-erb B2, hst and bcl-1 were not expressed at al l. No Ki-ras or N-myc amplification was observed, nor was any rearrang ement of the above-mentioned oncogenes found. Clinical correlation exi sted between tumor stage and oncogene amplification: patients with sta ge I and II disease (IUCC,AJCC) showed no amplification at all, wherea s 14 patients with stage III and IV disease showed amplified oncogenes (P = 0,015, chi2-test). In contrast, there was no correlation between oncogene amplification and disease development (observed over a minim um period of 3 years), nor could amplification be correlated with othe r clinical parameters (sex, tumor site, -histology) for any of the onc ogenes. Present findings suggest that oncogene amplification in head a nd neck squamous cell carcinomas is a later acquired epiphenomenon of tumor progression but has no obvious clinical correlation at this time .