In the present study, amplification status of CCND1 and expression of CyclinD1 were evaluated by fluorescence in situ hybridization and immunohistochemistry on tissue microarrays from 152 lymph node-positive urothelial bladder cancers (one sample each from the center and invasion front of the primary tumors, two samples per corresponding lymph node metastasis) treated by cystectomy and lymphadenectomy.
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.
We also demonstrated that the AA genotype was associated with the occurrence of lymph node metastases (OR =3.26) and a higher level of cyclin D1 overexpression.
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.
The abnormal expression of β-catenin and the overexpression of cyclin D1 were correlated, and the overexpression of c-myc was correlated with tumor size, histological grade, clinical TNM stage and lymph node metastasis.
Immunohistochemistry for cyclin D1 and DNA flowcytometry for cell cycle parameters was done on paraffin embedded tumour samples from 45 patients with OSCC RESULTS: Higher expression of cyclin D1 was observed only in 30 (66.6%) of 45 cases that correlated with advanced age (P <0.02), higher tumour stage (P<0.01), histological differentiation and lymph node metastasis (P <0.01).
These analyses also showed that a high TACSTD2 expression (P=0.003), a high Cyclin D1 expression (P=0.041), and lymph node metastasis (P=0.006) were independent prognosis factors.
In conclusion, CCND1 is amplified and overexpressed in a substantial proportion of vulvar carcinomas and associated with the occurrence of locoregional lymph node metastases, especially in human papillomavirus-negative tumors.