Amplification of cyclin D1 in squamous cell carcinoma of the head and neck and the prognostic value of chromosomal abnormalities and cyclin D1 overexpression

Abstract

Abnormalities of chromosome band 11q13 are frequent in squamous cell carcinoma of the head and neck (SCCHN). The oncogene CCND1 is located at 11q13 and encodes cyclin D1, a cell cycle-regulating protein. The authors investigated the clinical relevance and associations between amplification and overexpression of cyclin D1 and 11q13 rearrangements. The study involved two series of patients. In Series 1, overexpression of cyclin D1 and 11q13 rearrangements, assessed by immunohistochemistry and cytogenetics, respectively, were compared with clinical data in 75 patients with SCCHN. Patients were monitored for 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 cytogenetics. In Series 1, 9 of 75 tumors (12%) had 11q13 aberrations, 6 of which manifested elevated expression of cyclin D1. Patients with tumors strongly positive for cyclin D1 (n = 9) and those with tumors showing 11q13 rearrangements had poorer survival (P = 0.047 and 0.005, respectively). However, the correlation between these two variables was weak (P = 0.12). In Series 2, 17 of 23 tumors (74%) showed elevated cyclin D1 protein expression, and 6 of these showed gene amplification as well. Of these six, only one revealed 11q13 rearrangements. Overexpression of cyclin D1 and 11q13 rearrangements are independent prognostic factors for SCCHN. In general, DNA amplification results in overexpression of cyclin D1, but additional genetic mechanisms are involved in the deregulation. Furthermore, oncogenes at 11q13 besides CCND1 may be involved in the tumorigenesis.