Fifty Stage heterogeneous urinary bladder carcinomas were immunostaine
d for cathepsin B, a lysosomal endoproteinase putatively associated wi
th tumor invasion. Neoplastic cell CB immunoreactivity was strongly co
rrelated to both grade (I/II-42% positive versus III-68% positive, P =
0.01) and invasion beyond the lamina propria (Ta/T1-42% positive vers
us T2/T3-68% positive, P = 0.02). Most low grade, papillary tumors dis
played a granular cytoplasmic staining pattern, compatible with lysoso
mal distribution, in contrast to high grade tumors, in which diffuse s
taining was present in the cytoplasm. Staining was also accentuated at
the advancing front of invading tumors and in angiolymphatic tumor em
boli. Non-neoplastic mononuclear inflammatory cells, particularly thos
e at the host-tumor interface, displayed variable, sometimes intense s
taining. Strong tumor-cell CB was more frequent among recurrent TCC th
an in patients who remain free of disease (55% versus 29%, n = 18, T2-
3, cystectomy, 5-yr min. follow-up). We conclude these observed staini
ng patterns and grade/stage associations are compatible with an import
ant biological role for CB in facilitating host invasion in some bladd
er tumors. Levels and/or distribution of CB may also be of potential v
alue in defining clinically aggressive tumor subsets.