Relationship between expression of the KAI1 metastasis suppressor and other markers of advanced bladder cancer

Expression of a newly described inhibitor of tumour metastasis, KAI1, was e xamined in bladder cancer progression and compared with the expression of p 53 and pRb, which are markers of advanced disease. KAI1 mRNA (by in situ hy bridization) and protein levels (by immunohistochemistry) were examined in 135 paraffin-embedded bladder tissue sections, Significant decreases in KAI 1 mRNA and protein levels were detected between normal and tumour tissue (p < 0.001 and p = 0.026, respectively), and between non-invasive and invasiv e tumours (p = 0.046 and p < 0.001, respectively). Loss of KAI1 protein exp ression was accompanied by a shift in staining pattern from a uniform distr ibution to a weaker, membranous or heterogeneous pattern. Normal tissue and low-grade tumours showed little p53 protein staining. High level staining (indicative of mutant p53) was associated with increased grade in non-invas ive tumours (p = 0.031) but was not significantly higher in invasive tumour s, Whilst p53 protein staining increased with malignant progression and KAI 1 mRNA expression decreased, there was no significant correlation between t he two patterns (p = 0.33, adjusted for group, p = 0.18) or when only cance r samples were analysed (p = 0.065, adjusted for group, p = 0.26), even whe n taking into account overexpression of MDM-2 protein as a pathway for inac tivation of p53, There was no correlation between loss of KAI1 mRNA express ion and gain of abnormal pRb staining (p = 0.30, or adjusted for tumour sam ples only, p = 0.59). These results suggest that loss of KAI1 expression is associated with invasive bladder cancer, but is not related to mutation of p53 or to loss of normal pRb expression. Copyright (C) 2000 John Wiley & S ons, Ltd.