We report that Pin1 mRNA correlates with Cyclin D1 mRNA expression and the expression of many cyclin genes is associated with lymph node metastasis in OSCC.
A significant relationship was noted between amplification of cyclin D1 and lymph node metastases (p<0.05) but not with histological grade (p>0.05), estrogen receptor status (p>0.05) and proliferation index (Ki-67 and PCNA) (p>0.05).
Overexpression of cyclin D1 occurs in several malignancies, often due to gene amplification, and this has been associated with aggressive tumor behavior, a higher incidence of lymph node metastases, and a poorer prognosis.
Positive immunostaining of cyclin D1 and p21WAF1/CIP1 was not related to high-risk factors (pelvic lymph node metastasis, deep cervical stromal invasion, parametrial invasion, large tumor size, and unusual histologic type) and human papilloma virus infection.
Furthermore, the SI of cyclin D1 in carcinomas with lymph node metastasis was higher than in carcinomas without metastasis and was higher in advanced carcinomas than early carcinomas.
Amplification of the bcl-1/cyclin D1 locus was detected in 12 of the 49 LSCCs investigated (approximately 24%), 7 of which had lymph node metastases (approximately 58%); of the remaining 37 LSCCs with an apparently normal copy number of the cyclin D1 locus, 12 had lymph node metastases (approximately 32%).
The loss of heterozygosity correlated with advanced local invasion (P=0.0045), lymph node metastases (P=0.0326), stage IV of the tumors (P=0.0058), and existence of cyclin D1 amplification/overexpression (P < 0.03).
Two of the five patients positive for p53 mutations had clinical relapses of primary tumors. bcl-1 locus amplification only was observed in patients with lymph node metastases (4/6).