Association between the expression pattern of p16, pRb and p53 and the response to intravesical bacillus Calmette–Guerin therapy in patients with urothelial carcinoma in situ of the urinary bladder

Abstract

There is limited data regarding the association between the expression of cell cycle-regulating molecules and the response of patients with urothelial carcinoma in situ (CIS) to bacillus Calmette-Guerin (BCG) therapy. To examine the relationship between p16, pRb and p53 expression in bladder CIS and patient response to initial BCG therapy, we performed immunohistochemical studies for 27 patients with bladder CIS. Overexpression of p16, pRb, and p53 was observed in 37%, 41%, and 48% of patients, respectively. Initial BCG therapy was effective in 21 patients (78%). Coexistence of papillary urothelial carcinoma, depth (pTa or pT1) and grade of coexisting papillary carcinoma did not affect the response to BCG therapy. pRb overexpression had a significant relationship to poor response to BCG therapy (P= 0.027). The results of this study indicate that overexpression of pRb in bladder CIS predicts poor response of intravesical BCG instillation and status of p16 and p53 may not be predictive of initial BCG failure.

Lymphovascular invasion status at transurethral resection of bladder tumors may predict subsequent poor response of T1 tumors to bacillus Calmette-Guérin

“…Therefore, it is critical to identify the subset of T1 NMIBC patients whose tumors are highly malignant and have the potential to progress to muscle invasive disease. Various biological markers (such as p16, pRb, p53, MIB-1, and HSP90) have been studied for identifying aggressive T1 tumors [ 27 – 29 ], but these are relatively expensive and require additional procedures for histopathological analysis. In contrast, LVI can easily be investigated during standard histopathological evaluation.…”

Systemic transduction of p16INK4A antitumor peptide inhibits the growth of MBT-2 mouse bladder tumor cell line grafts

“…The findings described above support the application of the intravesical instillation of a p16 peptide to prevent the implantation of floating tumor cells after transurethral resection, since its instillation is similar to an in vitro peptide transfer. Of note, Sato et al (16) reported that the overexpression and phosphorylation of pRb in bladder tumor cells predicts a poor response to BCG therapy. Thus, combined therapy by p16 peptide transfer with BCG instillation may be a promising treatment for non-muscle-invasive bladder tumors, since restoring pRb function by p16 peptide transduction may be effective in treating BCG-refractory bladder tumors.…”

Immunocytochemical staining for p53 and Ki‐67 helps to characterise urothelial cells in urine cytology

“…Detected through immunocytochemistry, nuclear p53 expression is generally indicative of p53 gene mutation responsible for its nuclear accumulation . The mutation of p53 is thought to be an early event in the development of urothelial dysplasia and in in situ carcinoma . It has also been identified as a predictive marker for bladder tumours with a high risk of progression .…”