FREQUENT AMPLIFICATION OF 11Q13 DNA MARKERS IS ASSOCIATED WITH LYMPH-NODE INVOLVEMENT IN HUMAN HEAD AND NECK SQUAMOUS-CELL CARCINOMAS

Amplification of 11q13 DNA markers, particularly hst-1/FGF4 oncogene a nd the bcl-1 locus, was evaluated in 178 head and neck squamous cell c arcinomas (SCCs) by Southern blot and slot blot hybridisation. Coampli fication of hst-1/FGF4 and bcl-1 genes was found in 57% of primary tum ours and in 60% of the 89 metastatic lymph nodes tested. The pattern o f amplification was significantly similar in matched sets of primary S CCs and metastatic lymph nodes. Levels of amplification, quantified by densitometric analysis of slot blots, ranged from 2 to 18-fold normal gene dosage. Also, c-myc oncogene (8q24) was found amplified less fre quently, since 7% of 169 SCCs tested contained amplification of this g ene, the level of which ranged from 2 to 8-fold. Hst-1/bcl-1 gene ampl ification was observed more frequently in the tumours arising from the hypopharynx. Coamplification of hst-1 and bcl-1 genes was significant ly positively associated with tumours with nodal involvement (P = 0.00 1). Incidence of hst-1/bcl-1 gene amplification is higher in the tumou rs with a clinical stage III or IV. Hst-1/bcl-1 gene amplification was not related to tumour differentiation or local invasiveness. This pro spective study shows that amplification of 11q13 DNA markers is a prom inent event occurring in head and neck SCC and may contribute to the p athogenesis and evolution of a subset of patients bearing this type of cancer.