Expression of key proteins in the MEK/ERK pathway, including p-p52Shc, Shc·Grb2 complexes, p-MEK, p-ERK, and cyclin D1, was significantly higher in patients with advanced FIGO stage, high grade, and lymph-node metastasis and correlated positively with serum insulin concentration.
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.
However, no marked difference was noted in cyclin D1 expression between males and females, among patients in different age groups and between patients with and without lymph node metastasis (P>0.05).
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.
Among patients with muscle-invasive UCB, increased cyclin D1 expression in tumor cells significantly correlated with lymph node metastasis (p<0.001), and there was a trend of cyclin D1 together with lymph node positivity to be associated with disease recurrence (p=0.678).
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.
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.
In addition, amplification of CCND1 shows a negative predictive value of 80 % in the detection of LNM in early stage OSCCs which are clinically lymph node negative although this evidence is sparse and should be validated in a larger homogeneous cohort of T1-2 OSCC.