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The original pre-treatment histological sections from 125 patients with invasive (T2/T3) transitional cell bladder cancer treated by radical radiotherapy were studied; 63 tumours responded completely to radiation and 62 did not; 55 of 72 tumours containing areas of squamous metaplasia and 27 of 36 staining for beta-human chorionic gonadotrophin failed to respond to radiotherapy; 26 of 28 tumours showing both squamous metaplasia and beta-human chorionic gonadotrophin did not respond to radiation, whereas 40 of 45 tumours without either of these features responded. The DNA ploidy of 86 tumours in the series was measured by flow cytometry; 11 of 27 aneuploid and 30 of 59 diploid tumours responded to irradiation. Squamous metaplasia and beta-human chorionic gonadotrophin in bladder cancer indicate resistance to radiotherapy but DNA ploidy does not.

A retrospective analysis of the prognostic value of pretreatment histology and expression of human chorionic gonadotrophin (B-hCG) was carried out in 100 invasive (T2/T3) transitional cell carcinomas of the bladder treated in a uniform manner. After transurethral resection of the tumour, all patients received a course of radical radiotherapy, with salvage cystectomy for those who failed to respond. Forty-nine of 100 patients responded to radiation; thus 51 did not. Forty-seven of 60 (78%) patients whose tumours contained areas of squamous differentiation and 22 of 29 (76%) of tumours staining positively for HCG failed to respond to radiotherapy. Twenty-two of 23 (96%) patients with tumours that had both these features did not respond to radiotherapy. The other histological features studied (grade of tumour, necrosis, inflammation, vascular invasion, and growth pattern) appeared unrelated to each other or to clinical outcome.

We assessed the staining characteristics of the basement membrane of transitional cell carcinoma of bladder using a monoclonal antibody to type IV collagen. Basement membranes were clearly stained at the stromal/carcinoma interface. As transitional cell carcinoma became less well differentiated and the depth of invasion increased interruptions to basement membrane staining became more extensive and these findings are comparable to those described in similar series of transitional cell carcinoma using polyclonal antibodies to type IV collagen. The defects in basement membrane staining may be related to the degree and direction of tumour cell differentiation or may be explained by increased degradation compared to synthesis of basement membrane components. Demonstration of the basement membrane may be of value in diagnostic histopathology as a marker of the biological behaviour of transitional cell carcinoma of bladder.

One hundred cases of transitional cell carcinoma of the bladder were studied to determine whether squamous metaplasia and other histological features within the bladder can be of value in predicting outcome of treatment with radiotherapy. Sixty cases showed the changes of squamous metaplasia, and of this group 46 (78%) failed to respond to radiotherapy. A significant response rate of 90% was seen in the 40 tumours without squamous metaplasia. It is concluded that transitional cell carcinomas of the bladder showing squamous metaplasia are mainly resistant to radiotherapy and alternative treatment methods should be sought.