Bladder squamous cell carcinomas express psoriasin and externalize it to the urine

Purpose: To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), a calcium binding protein which is expressed largely by stratified squamous epithelia and is externalized to the urine of bladder squamous cell carcinoma (SCC) bearing patients. Materials and Methods: Protein expression profiles of SCCs obtained immediately after surgery were analyzed by two-dimensional gel electrophoresis and Coomassie blue staining. Protein identity was determined by microsequencing and immunoblotting. Protein expression in cryosections was studied by immunofluorescence. Results: Four patients with SCC were identified from 100 samples of patients with suspected transitional cell carcinoma (TCC). The protein profiles of the 4 SCCs (56-1, grade III, T4; 181-1, grade I, T3; 219-1, grade III, T3 and 239-1, grade not determined, T2-4) resembled that of keratinocytes, suggesting that these cells express an early developmental pattern of gene expression. Besides expressing markers characteristic of keratinizing stratified squamous epithelia, the SCCs exhibited psoriasin, a protein externalized to the medium by keratinocytes. Immunohistochemistry of 3 of the SCCs with psoriasin antibodies showed that the positive cells were confined chiefly to the ''squamous pearls.'' The presence of psoriasin in the urine of the 4 SCC patients was demonstrated by two-dimensional gel immunoblotting. Similar analysis of 43 urines from patients with bladder tumors other than SCC revealed 7 positives, some of which may reflect squamous differentiation. Analysis of the urine of 13 control individuals (12 males matched by age and a 42-year-old female) revealed 2 positives. Immunoblotting of the SCC patients' serum proteins with psoriasin antibodies failed to reveal the protein. Conclusion: The results point towards psoriasin, alone or as part of a biomarker profile, as a potential marker for the noninvasive follow-up of patients with SCC.