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

Background. CCND1 is a putative oncogene, often amplified in squamous cell carcinoma of the head and neck (SCCHN). The gene is located on chromosomal band 11q13 and encodes cyclin D1, a cell cycle-regulating protein involved in the G1/S transition. Material and methods. We evaluated overexpression of cyclin D1 and rearrangements of 11q13 as prognostic factors in 75 patients (series 1). Furthermore, we investigated the association between cyclin D1 overexpression, amplification, and cytogenetics in another 23 cases (series 2). Overexpression was detected immunohistochemically, and DNA amplification by slot blot hybridization. Cytogenetics was performed after short-term culture. Results. Series 1: Nine of 75 tumors (12%) were strongly cyclin D1 positive, and 9 (12%) had 11q13 aberrations. Patients with tumors strongly positive for cyclin D1, and those with tumors showing 11q13 rearrangements had shorter 2-year survival (p = 0.047 and p = 0.005, respectively). However, the correlation between these two parameters was weak (p = 0.12). Series 2: Of 23 tumors, 17 (74%) manifested elevated cyclin D1 protein expression, six of which showed gene amplification. Of these six, one revealed 11q13 rearrangements. There was a weak correlation between amplification and elevated expression (p = 0.15). Conclusions. Overexpression of cyclin D1 and rearrangements of 11q13 are independent prognostic factors in SCCHN. Other genes on 11q13 than cyclin D1 may be involved in tumorigenesis. Other genetic mechanisms along with amplification are involved in the deregulation of cyclin D1.