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PRAD-1/Cyclin D1 Gene Amplification Correlates with Messenger RNA Overexpression and Tumor Progression in Human Laryngeal Carcinomas¹

Department of Anatomic Pathology [P. J., P. L. F., E. C., A. N., F. B., G. A., I. N., A. C.]; Postgraduate School of Hematology Farreras Valenti [F. B.]; Department of Otolaryngology, Hospital Clínic, University of Barcelona, Barcelona, [J. T.] and Department of Basic Medical Sciences, University of Lleida, Lleida [P. J., E. C.], Spain

PRAD-1 is a putative oncogene localized on chromosome 11q13 which encodes cyclin D1, a novel cyclin involved in cell cycle regulation. Amplification of this gene has recently been reported in several human tumors including breast and head and neck carcinomas. In this study we have analyzed the presence of PRAD-1/cyclin D1 gene amplification and mRNA overexpression in a series of 46 matched normal mucosas and squamous cell carcinomas of the larynx. PRAD-1/cyclin D1 was found to be amplified 2- to 12-fold in 17 carcinomas (37%). DNA amplification correlated with advanced local invasion (P = 0.0015), presence of lymph node metastases (P = 0.0078), and stage IV of the tumors (P = 0.0021). mRNA overexpression was found in 15 of the 43 (35%) cases examined and it was also significantly associated with advanced local invasion (P = 0.0025) and stage IV carcinomas (P = 0.0032). A significant association was observed between gene amplification and mRNA overexpression (P < 0.0001) with only 3 discordant cases (2 amplifications with no overexpression and 1 overexpressed carcinoma with no gene amplification). Furthermore, the degree of DNA amplification correlated with the levels of mRNA expression (r = 0.6; P = 0.024). These findings suggest that the PRAD-1/cyclin D1 gene may be an important target of 11q13 amplifications in laryngeal carcinomas and the activation of this gene may be involved in the progression of these tumors. Its association with advanced-stage tumors indicates that PRAD-1/cyclin D1 gene amplification and overexpression may be of prognostic significance.

¹ This study was supported by grant SAF 1195/93 from DGICYT, Ministerio de Educación y Ciencia, and FIS 93/1012, Ministerio de Sanidad, Spain.

² Fellow of the Spanish Ministerio de Educación y Ciencia.

³ To whom requests for reprints should be addressed, at Department of Anatomic Pathology, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.

⁴ Supported by a grant from Hospital Clínic of Barcelona.

⁵ Holds Research Fellowships from the Hospital Clínic of Barcelona and the Postgraduate School of Hematology Farreras-Valentí & Schering Plough, Spain.

⁶ Supported by a grant from CIRIT, Generalitat de Catalunya.

Received 5/26/94. Accepted 6/30/94.

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