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


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.


CONCLUSIONS
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.
Celis
J E
JE
Department of Medical Biochemistry, University of Aarhus, Denmark.
Rasmussen
H H
HH
Vorum
H
H
Madsen
P
P
Honoré
B
B
Wolf
H
H
Orntoft
T F
TF
D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000652:urine*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis / Q000652:urine*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000652:urine; D016022:Case-Control Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D001743:Urinary Bladder / Q000737:chemistry; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000652:urine
D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human