Using a novel approach, we tested these hypotheses in the present study by examining p16 and pRb status in primary culture (P0) and after passage in vitro of transitional cell carcinoma (TCC) biopsies that represented both superficial bladder tumors and invasive bladder cancers.
We looked for p16/p19 deletion and p16 promoter methylation, as well as loss of 9p21 heterozygosity in pure squamous cell carcinomas (SCC), and in transitional cell carcinomas (TCC) of the bladder with SCC components.
Tissue samples from 67 patients with transitional cell carcinoma were examined with an immunohistochemical stain for the expression of p16 and cyclin D1 genes.
Based on the concept that tumor suppressor genes are involved in the pathogenesis of urinary bladder carcinogenesis, we analysed the mRNA expression of the retinoblastoma (Rb) and p16 (CDKN2, INK4A, MTS1) genes as well as of the proto-oncogene cyclin D-dependent kinase 4 (CDK4) in 71 transitional cell carcinomas (TCC) of the urinary bladder in relation to the tumor grades and stages, and with reference to certain lifestyle and occupational risk factors.
Of the entire group, p15 and p16 alteration and positive TGF-alpha (> or =cutoff value) were significantly expressed in schistosomal bladder cancer (68.1%, 60.9%, and 65.2%), and squamous cell carcinoma type (SCC) (69.1%, 64.7% and 72.1%) compared to those with non-schistosomal bladder cancer (29.4%, 7.8%, and 37.3%) or transitional cell carcinoma (TCC) (28.8%, 3.8%, and 28.8), respectively.
Our data suggest that HPV does not play a role in the development of squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation. p16 expression should not be used as a surrogate marker for evidence of HVP infection in either squamous cell carcinoma of the urinary bladder or urothelial carcinoma with squamous differentiation as neither HVP DNA nor protein is detectable in these neoplasms.
To determine the potential association between HPV infection and the squamous cell component of urothelial carcinoma (UC) of the bladder and to validate p16 overexpression as a surrogate marker for HPV infection in these cancers among Koreans.
To detect recurrent pagetoid urothelial intraepithelial neoplasia with pagetoid spread in the lower genital tract, pathologists should recognize the history of prior UC with special attention to absence of p16 labeling in cervical cytology as a pointer to the diagnosis of urothelial cancer.