Chorionic gonadotropin beta-subunit and core fragment in bladder cancer: mRNA and protein expression in urine, serum and tissue.
OBJECTIVE
Many transitional cell carcinomas (TCC) of the bladder express the beta-subunit (CGbeta) of chorionic gonadotropin (CG), and elevated serum levels occur especially in advanced disease. We have compared the diagnostic utility of various methods for detecting CG and CGbeta expression at the protein and mRNA level.


METHODS
We used RT-PCR to detect CGbeta mRNA in urinary cells and highly sensitive immunoassays to determine CG and CGbeta in serum and the core fragment of CGbeta (CGbetacf) in urine from patients under follow-up for bladder cancer. Tissue expression was studied by immunohistochemistry.


RESULTS
CGbeta mRNA was detected in urinary cells in 50% (n=84) of the cancer cases and in none of the healthy controls (n=15). Positive staining for CGbeta in tissue samples was observed not only in 30% (n=96) of the TCC cases, but also in 5 of 20 histologically benign samples from TCC patients, and in 10 of 21 samples from benign bladder diseases. Serum and urinary concentrations of CGbeta were elevated in 29% (n=66) and 8% (n=72), respectively, while serum CG was elevated in 18% of the TCC patients. Urinary CGbetacf concentrations were higher in invasive (T1-T4) than superficial (T in situ and Ta) tumors (p=0.037), in cases positive for CGbeta mRNA (p=0.03) and cases with suspicious or malignant urinary cytology (p=0.002). The ratio of urinary to serum concentration of CGbeta showed the strongest correlation with tumor stage (p<0.00001), grade (p<0.00001), and staining for CGbeta (p=0.019).


CONCLUSIONS
Although CGbeta expression may occur in benign bladder epithelium, CGbeta mRNA in urinary cells is a potential marker of bladder cancer. Urinary and serum CGbeta have low sensitivity in early disease, but the urine/serum ratio appears to indicate local release of CGbeta into urine. Further studies are needed to evaluate the clinical usefulness of different forms of CGbeta expression.
Hotakainen
Kristina
K
Biomedicum Helsinki, Room A418a, Helsinki University Central Hospital Research Laboratory, PB 700, 00029, HUCH, Finland. kristina.hotakainen@hus.fi
Haglund
Caj
C
Paju
Annukka
A
Nordling
Stig
S
Alfthan
Henrik
H
Rintala
Erkki
E
Stenman
Ulf-Håkan
UH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*
D014408:Biomarkers, Tumor; D018997:Chorionic Gonadotropin, beta Subunit, Human; D010446:Peptide Fragments; D012333:RNA, Messenger; C063554:urinary gonadotropin fragment