p53 and RB Expression Predict Progression in T1 Bladder Cancer

Level of retinoblastoma protein expression correlates with p16 (MTS-1/INK4A/CDKN2) status in bladder cancer

“…It is well known that hypermethylation involving p16 is a frequent mechanism for loss of p16 expression in several common cancers (Merlo et al, 1995;Reed et al, 1996;Wong et al, 1997) but is substantially less frequent in bladder cancer (Spruck et al, 1994). However, regardless of the mechanism, our data support the hypothesis that loss of p16 protein expression is associated with the overexpression of RB recently reported to have similar biological and clinical signi®cance as loss of RB expression in bladder tumors (Cote et al, 1998;Grossman et al, 1998). Moreover, the relationship between overexpression of RB and loss of p16 function also may extend to other tumor types, particularly to those tumor types for which loss of RB function has been implicated as a key factor in their progression including osteosarcomas, ®brosarcomas and non-small cell lung carcinomas (Benedict et al, 1990).…”

“…Nevertheless, despite including RB overexpressors in the normal RB group, patients with alterations in RB still showed a marked increase in progression and decrease in survival rate compared to those individuals whose tumors were scored as RB negative. Because of the similarity in the ®ndings between this study (CordonCardo et al, 1997) and the other report on super®cial tumors (Grossman et al, 1998) in which both absent and overexpression of RB was scored as abnormal, it is likely that there were few, if any, strong RB (presumably p16 negative) staining cases in the ®rst study (Cordon-Cardo et al, 1997) to be misinterpreted as having normal RB function. This is consistent with our yet unpublished observations indicating that most super®cial tumors, particularly Ta lesions, have a heterogeneous staining pattern for both p16 and RB.…”

“…As stated previously, these latter two studies used the same criteria and methodology to determine the RB status in bladder tumors as was utilized in our present report. It was found that patients whose tumor overexpressed RB protein had a similar increased progression rate and a decreased overall survival as individuals whose tumor was RB negative (Cote et al, 1998;Grossman et al, 1998). This relationship was seen for both super®cial and highly invasive tumors.…”

“…The protocol for staining RB nuclear protein has been previously described (Xu et al, 1996, Grossman et al, 1998. Brie¯y, after hydrogen peroxide treatment (0.3% in absolute methanol for 30 min) to block the endogenous peroxide activity, the slides were washed in glass distilled water and placed in 0.01 M sodium citrate bu er (pH 6.0) for 15 min at 958C, which was followed by rinsing in distilled water and PBS.…”

“…Moreover, loss of RB function has been associated with progression to invasive disease and decreased survival (Cordon-Cardo et al, 1992;Logothetis et al, 1992). In addition it was recently found that patients whose bladder cancer showed overexpression of RB protein by immunohistochemical (IHC) analysis had an increased rate of progression and decreased survival rate comparable to those patients with tumors exhibiting no RB protein expression (Cote et al, 1998;Grossman et al, 1998). These ®ndings suggest that bladder tumors with a strong, homogeneous staining pattern may re¯ect abnormal RB status resulting in a similar pathological e ect as those tumors with absent RB protein expression.…”