AMPLIFICATION OF CYCLIN D1 IN SQUAMOUS-CELL CARCINOMA OF THE HEAD ANDNECK AND THE PROGNOSTIC VALUE OF CHROMOSOMAL-ABNORMALITIES AND CYCLIND1 OVEREXPRESSION

BACKGROUND. Abnormalities of chromosome band 11q13 are frequent in squ amous cell carcinoma of the head and neck (SCCHN). The oncogene CCND1 is located at 11q13 and encodes cyclin D1, a cell cycle-regulating pro tein. The authors investigated the clinical relevance and associations between amplification and overexpression of cyclin D1 and 11q13 rearr angements. METHODS. The study involved two series of patients. In Seri es 1, overexpression of cyclin D1 and 11q13 rearrangements, assessed b y immunohistochemistry and cytogenetics, respectively, were compared w ith clinical data in 75 patients with SCCHN. Patients were monitored f or at least 18 months or until death. In another 23 patients (Series 2 ), the authors investigated the association between DNA amplification (by slot blot hybridization), overexpression of cyclin D1, and cytogen etics. RESULTS. In Series 1, 9 of 75 tumors (12%) had 11q13 aberration s, 6 of which manifested elevated expression of cyclin D1. Patients wi th tumors strongly positive for cyclin D1 (n = 9) and those with tumor s showing 11q13 rearrangements had poorer survival (P = 0.047 and 0.00 5, respectively). However, the correlation between these two variables was weak (P = 0.12). In Series 2, 17 of 23 tumors (74%) showed elevat ed cyclin D1 protein expression, and 6 of these showed gene amplificat ion as well. Of these six, only one revealed 11q13 rearrangements. CON CLUSIONS. Overexpression of cyclin D1 and 11q13 rearrangements are ind ependent prognostic factors for SCCHN, In general, DNA amplification r esults in overexpression of cyclin D1, but additional genetic mechanis ms are involved in the deregulation. Furthermore, oncogenes at 11q13 b esides CCND1 may be involved in the tumorigenesis. (C) 1997 American C ancer Society.