Molecular and immunohistochemical analysis of the bcl-1/cyclin D1 gene in laryngeal squamous cell carcinomas: correlation of protein expression with lymph node metastases and advanced clinical stage

BACKGROUND. The molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs) is still only partially understood, although genetic alterations affecting various protooncogenes or tumor suppressor genes have often been detected. METHODS. To improve their understanding of the role of cyclin D1 in the pathogenesis of LSCCs, the authors investigated the expression of cyclin D1 protein and the amplification status of the bcl- 1/cyclin D1 locus in a panel of 58 pathologic samples. RESULTS. Expression of cyclin D1 protein was detected in 23 of the 58 patients (≃39%), 14 of whom had lymph node metastases (≃61%); of the remaining 35 patients without any detectable cyclin D1 expression, 7 had lymph node metastases (20%). Expression of cyclin D1 was detectable in 5% of the specimens of normal mucosa, 13% of those wild mild-to-moderate dysplasia, and 25% of those with severe dysplasia. Amplification of the bcl-1/cyclin D1 locus was detected in 12 of the 49 LSCCs investigated (≃24%), 7 of which had lymph node metastases (≃58%); of the remaining 37 LSCCs with an apparently normal copy number of the cyclin D1 locus, 12 had lymph node metastases (≃32%). The authors found almost complete concordance between locus amplification and protein expression. Statistical analysis showed a correlation between cyclin D1 expression and both the presence of lymph node metastases (P < 0.01) and advanced clinical stage (P < 0.02). CONCLUSIONS. The authors' observations suggest that the deregulation of cyclin D1 expression may be involved in the pathogenesis of more aggressive LSCCs.