Expression of p16 and cyclin D1 in bladder cancer and correlation in cancer progression.
BACKGROUND
Gene p16 encodes a cyclin-dependent kinase inhibitor which functions to regulate cyclin D1, cell cycle progression and malignancies. The relationship between p16 and cyclin D1 is thought to alter bladder cancer formation and tumor progression. We aimed to investigate the expression of p16 and cyclin D1 genes in order to evaluate their clinical significance in bladder cancer.


METHODS
Tissue samples from 67 patients with transitional cell carcinoma were examined with an immunohistochemical stain for the expression of p16 and cyclin D1 genes. The expression rate was compared to 12 normal urinary bladder mucosa samples obtained from transurethral surgery from noncancer patients.


RESULTS
The results revealed significant differences between normal bladder mucosa (100%) and cancer tissue (40.3%) for the positive staining of p16 protein (p < 0.001), while positive staining for the cyclin D1 protein in the patient group (67.2%) was significantly higher (p = 0.003) than that in the control group (16.7%). With the progression of tumor grade and clinical staging the positive rate of p16 gene expression increased, whereas, that of cyclin D1 decreased. Expression of the p16 gene in the non-invasive group was greater than that in the invasive group and a lower expression rate of the cyclin D1 gene in the non-invasive group compared to the invasive group.


CONCLUSIONS
The results revealed that expression of the p16 gene is inversely proportional to the expression of the cyclin D1 gene. Therefore, abnormal expression of the p16 and cyclin D1 genes play important roles in tumorigenesis and tumor progression.
Yang
Ching-Chiang
CC
Department of Urology, China Medical College Hospital, China Medical College, Taichung, Taiwan.
Chu
Kang-Chu
KC
Chen
Huey-Yi
HY
Chen
Wen-Chi
WC
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001707:Biopsy, Needle; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D016001:Confidence Intervals; D046508:Culture Techniques; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
D014408:Biomarkers, Tumor; D019938:Cyclin D1