CDK4 is involved in the control of G1-S phase transition as a part of the CCND1/CDK4 complexes. CCNDI and CDK4 gene alterations have been implicated in the development of different tumors. CCND1 has been associated with progression in laryngeal carcinomas. CDK4 protein overexpression was described associated to CCND 1 overexpression in these tumors. However, the mechanisms implicated were not known. We analyzed CDK4 gene alterations and mRNA expression in a series of carcinomas of the larynx, and the results were compared to CCND1 expression and clinicopathological characteristics of the patients. CDK4 mRNA was overexpressed in 42 out of 60 tumors (70%) associated with CCND1 mRNA overexpression because 15 out of 16 cases with high CCND1 levels showed simultaneous increased levels of CDK4 mRNA (p = 0.023) and 12 (87%) of the tumors overexpressing both genes were in stage 4. No CDK4 gene amplifications, rearrangements, or mutations were detected in any of the tumors, including 24 overexpressed cases. These findings confirm that CDK4 overexpression is a frequent phenomenon in laryngeal carcinomas, which occurs at the transcriptional level but is related neither to gene amplification nor to gene mutation, and suggest that cooperation with CCND1 may be involved in the progression of laryngeal tumors.

Expression of both Ep-CAM and E48 correlated with cell differentiation, although in inverse fashion. In particular, the association between high levels of Ep-CAM expression and high frequency of nodal metastases suggests that Ep-CAM plays a role in the development of lymph node metastases in SCC of the larynx.