PRAD-1 (CCND1) CYCLIN D1 ONCOGENE AMPLIFICATION IN PRIMARY HEAD AND NECK SQUAMOUS-CELL CARCINOMA

Background. Abnormalities in chromosome 11q13 regions have been frequently found in head and neck squamous carcinoma. Recent studies indicate that the PRAD-1 (also CCND1), which encodes cyclin D1, is a putative oncogene that is an important component of this region. Methods. DNA was extracted from 32 snap-frozen specimens from primary head and neck squamous carcinomas. DNA from peripheral blood lymphocytes, normal mucosa, and salivary gland tissue were used as controls. A genomic DNA probe containing the first exon of PRAD-1 was used for hybridization with specimen DNAs by the Southern technique. A 5.6-kb genomic DNA probe of immunoglobulin heavy chain was used as an internal standard for assessing PRAD-1 amplification. Results. Eleven (34.4%) squamous carcinoma specimens showed PRAD-1 amplification (2- to 10-fold). Although no significant statistical correlation among amplification status, grade stage, and DNA ploidy was observed in this small cohort, amplification was more noted in high grade, high stage, and aneuploid tumors. A highly statistical correlation between PRAD-1 amplification and proliferative activity was noted (P > 0.001). Conclusion. The results of this study indicate that PRAD-1 amplification appears to be a late event in the tumorigenesis of head and neck carcinoma and is associated often with a subset of aggressive tumors and high proliferation neoplasms.