Immunohistochemical expression of Retinoblastoma gene product (Rb), p53 protein, MDM2, c-erbs-2, HLA-DR and proliferation indices in human urinary bladder carcinoma

Archival biopsy specimens from transitional cell bladder cancers (n=88) wer e analysed immunohistochemically for the expression of the retinoblastoma ( Rb) gene protein, p53, mdm2, c-erbB-2, HLA-DR antigen and proliferation ind ices. An altered nuclear expression of Rb, p53 and mdm2 was observed in 55. 2%, 33.3% and 18.2% of tumors respectively. Cytoplasmic membrane immunoreac tivity (>25% tumor cells) for c-erbB-2 was detected in 14.1% of tumors and aberrant HLA-DR antigen cytoplasmic staining (>5% of tumor cells) in 22.2% of the cases. P53 overexpression was associated with higher tumor grade and stage. Aberra nt HLA-DR antigen expression and PCNA were also correlated with the grade o f differentiation and tumor stage. MIB1 was statistically correlated with s tage. pRb scores and HLA-DR antigen expression were correlated with prolife ration activity as determined by PCNA and MIB1 immunostaining. p53 protein was also strongly correlated with the proliferation index PCNA. A strong co rrelation between PCNA and MIB1 (p<0.0001) was also found. In addition a st atistically positive correlation between p53 and HLA-DR antigen expression was observed. Our data show that, although pRb and p53 protein expressions are not associated between them, they may contribute to the growth fraction of the bladder cancer. In addition, p53 and HLA-DR antigen expression coul d be indicators of aggressive behavior of bladder cancer.