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

Abstract

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 (approximately 39%), 14 of whom had lymph node metastases (approximately 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 with 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 (approximately 24%), 7 of which had lymph node metastases (approximately 58%); of the remaining 37 LSCCs with an apparently normal copy number of the cyclin D1 locus, 12 had lymph node metastases (approximately 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.