Cyclin D1 gene numerical aberration is a predictive marker for occult cervical lymph node metastasis in TNM stage I and II squamous cell carcinoma of the oral cavity

BACKGROUND. The management of occult cervical lymph node metastases originating from oral squamous cell carcinomas (OSCCs) remains controversial. The purpose of this study was to evaluate the value of cyclin D1 gene(CCND1) numerical aberrations in predicting the risk of late lymph node metastases. METHODS. Fluorescence in situ hybridization (FISH), using a BAC clone specific for CCND1, was performed on OSCC specimens obtained by fine-needle aspiration (FNA) biopsy from 45 patients with previously untreated TNM Stage I and II (TI-2NOMO) disease who had not undergone elective cervical lymph node dissection. RESULTS. CCND1 numerical aberrations were observed in 15 (33.3%) of the 45 patients and were significantly associated with the mode of invasion of the primary tumor (P = 0.01) and the presence of occult lymph node metastases (P < 0.001). Twelve of these 15 patients (80%) developed late cervical lymph node metastases within 2 years of surgery for primary OSCCs. All patients with cluster-type amplification of CCND1 developed late lymph node metastases. Multivariate analysis showed that only CCND1 numerical aberrations (risk ratio, 8.685%, 95% confidence interval = 2.232-33.802, P = 0.002) independently predicted late cervical lymph node metastasis. CONCLUSIONS. Aberrations in CCND1 numbers appear to be valuable in identifying patients at high risk of late lymph node metastasis in Stage I and II OSCCs. Analysis of CCND1 numerical aberrations using FISH on FNA biopsy specimens may be useful in selecting patients for elective cervical lymph node dissection. (c) 2005 American Cancer Society.