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Abstract
The gene structure and expression of the related peptide regulatory factors TGF beta 1 and TGF beta 2 were studied in a panel of seven urothelial carcinoma cell lines and 40 transitional cell carcinomas. The latter comprised 15 grade 1, 18 grade 2 and 5 grade 3 tumours and two cases of carcinoma in situ. Control tissues included ten matched 'field' biopsies and 17 other biopsies including 11 biopsies of macroscopically normal urothelium, two of which were from patients with no history of bladder cancer. No amplification of rearrangements of either TGF beta 1 or TGF beta 2 were detected in any sample. A complex pattern of expression or the two genes was found in the urothelial cell lines. High, but variable levels of the 2.5 kb TGF beta 1 transcript were detected and lower and more variable levels of the three (4.1 kb, 5.1 kb and 6.5 kb) transcripts of TGF beta 2 were detected. Although those cell lines expressing most TGF beta 1 tended to express less TGF beta 2 transcript there was no clear-cut relationship. In comparison, no TGF beta 2 transcript was identified in any primary transitional cell carcinoma or control tissue. Markedly reduced or undetectable levels of TGF beta 1 transcript were detected in 4/15 (26%) grade 1, 5/18 (28%) grade 2 and 3/5 (60%) grade 3 tumours. There was no clear relationship to tumour stage, lymphocytic infiltration or stromal content of the tumours. Clinical review one year after the 2 year period of tumour collection showed that 6/9 (66%) of patients with tumours with reduced levels of transcript had died or had disease which was not controllable by local resection and 3/9 (33%) had developed tumour re-occurrences. In comparison, in the group with normal levels of expression of TGF beta 1, 3/18 (17%) had disease which was not controllable by local means, 9/18 (50%) had tumour re-occurrence and 6/18 (33%) had no evidence of disease. The association of reduced expression of TGF beta 1 and advanced disease was statistically significant P < 0.02 (Fisher's test). Although the sample size is small, we suggest that the loss of expression of TGF beta 1 may be a potential marker of progressive disease or prognosis in transitional cell carcinoma and warrants further study.
Highlights
The sample size is small, we suggest that the loss of expression of TGFP1 may be a potential marker of progressive disease or prognosis in transitional cell carcinoma and warrants further study
As part of a study aimed at identifying some of these lesions in transitional cell carcinoma, we have examined the structure and expression of the genes encoding TGFPi1 and TGFPi2 in human urothelial cancer cell lines and transitional cell carcinomas
All seven bladder tumour cell lines examined expressed high levels of TGFPIl mRNA of 2.5 kb (Figure la)
Summary
Tissue samples were collected from patients undergoing cystoscopic examination at University College Hospital, the Middlesex Hospital, the Shaftsbury Hospital and St Peters Hospital, London. Tumour size ranged from 60 mg to many grams but the majority (>80%) were small and were processed as a single sample. Where biopsies of normal urothelium or carcinoma in situ were taken, the epithelial layer was dissected free of submucosa and muscle. In these cases, urothelium from at least four biopsies from the same patient was pooled and processed together. Tissues were placed immediately at - 70°C. Tumours were graded according to W.H.O. recommendations (1973) and staged using the TNM system (UICC, 1978)
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