Image cytometry of cyclin D1: A prognostic marker for head and neck squamous cell carcinomas

CCND1 gene amplification and cyclin D1 protein overexpression are indicator s for poor prognosis in invasive head and neck carcinomas. Increased CCND1 gene dosage is a more sensitive prognostic factor than protein overexpressi on as evaluated by conventional immunohistochemical techniques. Qualitative immunohistochemistry cannot distinguish cyclin D1 overexpression accompani ed by amplification of the CCND1 gene from overexpression associated with n ormal CCND1 gene copy number. To improve the sensitivity of cyclin D1 prote in determination, We applied quantitative techniques of image analysis to e valuate cyclin D1 in 54 head and neck carcinomas. There was a significantly higher rate of occurrence of adverse events (P = 0.043) among patients wit h CCND1 gene amplification than among those without gene amplification, The re was a strong association between CCND1 gene amplification (as detected b y Southern blot analysis) and the highest nuclear score (by image cytometry of the immunostained tumor sections). The predominance of cells in the low est nuclear score category was significantly associated with normal copy nu mber (P = 0.005), Conversely, the highest nuclear score was a significant p redictor of gene dosage (P = 0.02), Similarly, high nuclear score was a goo d predictor of death as the final outcome of the disease (P = 0.01), Althou gh somewhat less accurate than Southern blotting, image cytometry of immuno histochemical cyclin D1 stain appears to be a promising tool that could be useful for other tumor marker expression studies.