“…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).…”