DNA Ploidy And The Expression Of P53 In Human Urothelial Carcinoma

Background There is no clear cut way to predict exactly which superficial urothelial carcinomas would subsequently not recur, which tumours would subsequently recur or progress after initial resection of the tumours. There is also no accurate way of predicting the outcome of muscle-invasive tumours urothelial following treatment Aims (a) To confirm the suggestion that aneuploidy is more common in urothelial tumours of high grade, high stage and is associated with inferior prognosis. (b) To find out if the combination of aneuploidy and over-expression of p53 would be more selective in predicting superficial tumours that would progress and in predicting muscle-invasive tumours of poor prognosis. Methods Correlation of the DNA ploidy state and the expression of p53 in human urothelial carcinoma was studied using flow cytometry and an immuno-histological (ABC) method. The ploidy state of 34 tumours were analysed with regards to grade, stage and outcome. The expression of p53 was also analysed with regards to grade, stage and outcome. Patients who had trans-urethral resection of bladder tumour had regular check cystoscopies with biopsies / resection of any recurrent tumours. Patients with muscle-invasive tumours who were treated by radiotherapy or cystectomy were reviewed regularly in the outpatient clinic and were assessed by clinical examination and ultrasound scan / CT scan of the abdomen pelvis and chest as may be required. They also had routine blood tests including: Full blood count; Serum urea and electrolytes; and liver function tests. Results Three out of 12 G1, 6 out of 9 G2 and 8 out of 12 G3 tumours respectively were aneuploid. Nine out of 12 G1, 3 out of 9 G2 and 4 out of 12 G3 tumours respectively were diploid. These results confirm the suggestion that aneuploidy is more commonly associated with urothelial carcinomas of high grade and high stage. All the 3 superficial tumours that progressed were aneuploid. However, the ploidy state of the tumours did not appear to have influenced the outcome of the muscle-invasive tumours. All the three superficial tumours that progressed were also observed to be moderately or strongly positively stained for p53. The three superficial tumours that progressed were therefore aneuploid and p53 positive. Aneuploidy and over-expression of p53 did not appear to have influenced the outcome of the muscle-invasive tumours. Conclusions These results confirm the suggestion that aneuploidy is more commonly associated with urothelial carcinomas of high grade and high stage. All the three Superficial tumours that progressed were aneuploid. All the three superficial tumours that progressed had over-expression of p53 (were moderately or strongly positive for p53) All the three superficial tumours that progressed were aneuploid as well as had over-expression of p53 Aneuploidy and over-expression of p53 did not appear to have influenced the outcome of muscle-invasive tumours.