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Rob J. A. M. Michalides, PhD; Nicoletta M. J. van Veelen; Petra M. P. Kristel; Augustinus A. M. Hart, MSc; Barbara M. Loftus, MRCPath; Frans J. M. Hilgers, MD; Alfons J. M. Balm, MD

Arch Otolaryngol Head Neck Surg. 1997;123(5):497-502.

Abstract
Objectives
To evaluate the overexpression of cyclin D1 and p53 as a prognostic marker of squamous cell carcinoma of the head and neck and to investigate whether deregulation of these genes is associated with an unfavorable course of disease.

Design
Retrospective study.

Materials and Methods
Formalin-fixed, paraffinembedded tumor materials that were obtained from a well-characterized series of 115 patients with resectable head and neck cancer at The Netherlands Cancer Institute, Amsterdam, were analyzed by immunohistochemical methods using antiserum samples that were directed against 2 proteins (ie, cyclin D1 and p53), which are crucial in the regulation of the G¹ phase of the cell cycle.

Results
Overexpression of cyclin D1 protein was found in 49% of the patients with squamous cell carcinoma of the head and neck. This overexpression was not associated with known prognostic factors (eg, the T and N stages). Tumors recurred more frequently and in a shorter period in patients whose primary tumors showed an overexpression of cyclin D1 protein. This difference (P=.05) was statistically significant in a stepwise proportional hazard regression analysis. However, since a discrepancy in staining results was observed between the biopsy and resection materials that were taken from the same patient, this result may not have been applicable in the evaluation of biopsy specimens only. This discrepancy is most likely owing to tissue heterogeneity. The overexpression of p53 that was found in 42% of the patients was of no prognostic significance.

Conclusions
These data provide evidence that overrexpression of cyclin D1 protein in resection material of squamous cell carcinomas of the head and neck is indicative of a poor prognosis, independently of other known prognostic factors. Whether overexpression of cyclin D1 may therefore be used to select patients for more intensive treatment should be examined in the context of a clinical trial.

Arch Otolaryngol Head Neck Surg. 1997;123:497-502

Author Affiliations
From the Division of Tumor Biology (Dr Michalides and Mss van Veelen and Kristel) and the Departments of Radiotherapy (Mr Hart), Pathology (Dr Loftus), and Otolaryngology/Head and Neck Surgery (Drs Hilgers and Balm), The Netherlands Cancer Institute, Amsterdam.

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