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2003;9:5642-5651. Published online December 3, 2003.Clin Cancer ResPere Puig, Paola Capodieci, Marija Drobnjak, et al.in Bladder Cancer

Expression Is Associated with Tumor Progressionof p73p73 Expression in Human Normal and Tumor Tissues : Loss

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p73 Expression in Human Normal and Tumor Tissues: Loss of

p73 Expression Is Associated with Tumor Progression in

Bladder Cancer

Pere Puig,1 Paola Capodieci,1 Marija Drobnjak,1

David Verbel,1 Carol Prives,2

Carlos Cordon-Cardo,1 and Charles J. Di Como1

1Division of Molecular Pathology, Memorial Sloan-Kettering Cancer

Center, New York, New York, and 2Department of BiologicalSciences, Columbia University, New York, New York

ABSTRACT

Purpose: To characterize the expression profile of p73

in human normal tissues by immunohistochemistry (IHC)and to analyze the correlation between p73 expression and

bladder cancer progression.

Experimental Design: CJDp73 was characterized for

p73 detection in Western blot and IHC through its appli-

cation to isoform-transfected 293 cells. Normal tissues were

analyzed by IHC with the CJDp73 antiserum. Transitional

cell carcinoma (TCC)-derived cell lines were subjected to

reverse transcription-PCR and Western blot. TCC tissue

microarrays were analyzed for p73 expression by IHC, and

the results were statistically analyzed.

Results: p73 immunostaining was nuclear and re-

stricted to epithelial cells of certain organs such as squamous

epithelium of the epidermis and transitional epithelium ofthe bladder. The expression was also observed in certain

specialized glandular epithelia such as acinar cells of breast

and parotid gland. Four of seven TCC-derived cell lines had

low to undetectable p73 protein levels. We found undetect-

able or low p73 expression in 104 of 154 (68%) TCC cases,

this phenotype being more frequently observed in invasive

tumors when compared with superficial lesions. This asso-

ciation was statistically significant (P < 0.0001). We also

observed a significant association between p53, p63, and

p73 alterations with bladder cancer progression (P