A combination of p40, GATA-3 and uroplakin II shows utility in the diagnosis and prognosis of muscle-invasive urothelial carcinoma.
Recently developed antibodies against uroplakin II and ΔNp63 (p40) show utility in diagnosing primary bladder urothelial carcinoma, although application in metastatic bladder cancer and patient outcomes has been less well defined. We evaluated these antibodies by immunostain intensity and H-score, in conjunction with GATA-3 immunoreactivity, in 89 patients with muscle-invasive urothelial carcinoma and 35 paired metastasis. The maintenance of immunoreactivity in metastatic lesions and the association to disease recurrence and survival was assessed. Bladder urothelial carcinoma showed immunoreactivity for GATA-3 in 99% (88/89), p40 in 87% (77/89) and uroplakin II in 80% (71/89) of cases, with a positive correlation between GATA-3 and uroplakin II H-score (0.44; p < 0.0001). All lesions were positive for at least one marker, reinforcing the use of these markers as a panel. In 35 patients with paired lymph node metastasis, uroplakin II and GATA-3 were retained in 90% and 75% of patients, respectively, suggesting these markers may have relatively high sensitivity in diagnosing metastatic urothelial carcinoma. High intensity p40 immunostain (3+), however, was significantly associated with reduced patient survival (p = 0.03). These results suggest that whereas GATA-3 and uroplakin II may be most useful in the diagnosis of urothelial carcinoma metastasis, p40 may be additionally suited as a prognostic marker.
Department of Pathology, University of California San Diego, La Jolla, CA, USA.
Mariah Z
MZ
Leivo
Quantitative Health Sciences Institute, Cleveland Clinic, Cleveland, OH, USA.
Paul J
PJ
Elson
Biocare Medical, Concord, CA, USA.
David E
DE
Tacha
Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington South, New Zealand.
Brett
B
Delahunt
Department of Pathology, University of California San Diego, La Jolla, CA, USA. Electronic address: dhansel@ucsd.edu.
Donna E
DE
Hansel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D050990:GATA3 Transcription Factor / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000096:biosynthesis*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D060170:Uroplakin II / Q000032:analysis / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C554658:UPK2 protein, human; D060170:Uroplakin II
Bladder cancer; GATA-3; immunohistochemistry; p40; survival; uroplakin II; urothelial carcinoma; ΔNp63