Chromosomal aberrations in transitional cell carcinoma that are predictive of disease outcome are independent of polyploidy

Objective To determine whether aneusomy for chromosomes 7, 9 and 17 (reported to predict recurrence in up to 65% of patients with superficial transitional cell bladder cancer and thus providing the opportunity for early and effective treatment) reflects specific genetic events on these chromosomes or merely wider unspecific genetic damage to the cell, e.g. that increased copy numbers for 7 and 17 reflect tumour polyploidy. Materials and methods The study comprised 25 primary tumours; 6 mu m thick sections from formalin-fixed and paraffin-embedded tumours were analysed. Chromosome copy numbers were determined by fluorescence in situ hybridization (FISH) using pericentromeric probes for chromosomes 7, 8, 9, 10, 11 and 17. A minimum of 200 nuclei per tumour area were scored by two independent observers. Results Eight of the 25 tumours examined (32%) showed no evidence of chromosomal abnormalities as detected by FISH for any chromosomes analysed. Twelve tumours (48%) showed abnormalities for one or two chromosomes, five tumours (20%) showed abnormalities for multiple chromosomes and one tumour showed abnormalities for all chromosomes analysed, suggestive of polyploidy. Conclusions Chromosomal abnormalities predictive of recurrence occur largely in the absence of other gross chromosomal lesions. In a small proportion of cases other chromosomes are affected, but this is almost always distinct from tumour polyploidy

Aneusomy of chromosomes 7 and 17 predicts the recurrence of transitional cell carcinoma of the urinary bladder

Objective To determine if changes in chromosome 7 and 17 copy number can be used to predict recurrence in patients with primary noninvasive (pTa) or superficially invasive (pT1) transitional cell carcinoma (TCC) of the urinary bladder. Patients and methods Tissue specimens for 129 tumours from 52 patients (38 men and 14 women) with pTa/pT1 TCC at first diagnosis were retrieved from pathology archives. All patient notes were accessed and disease outcome documented for superficial (pTa/ pT1) recurrence or progression to detrusor muscle invasion (greater than or equal to pT2). The rumours were examined for chromosomal copy number of chromosomes 7 and 17 using fluorescence in situ hybridization (PISH) with chromosome-specific probes. The copy number of chromosomes 7 and 17 was determined in interphase nuclei on intact 6 mu m tissue sections. Results Aneusomy of chromosomes 7 and 17 was detected in the index primary tumours of 10 of 32 (31%) patients with subsequent recurrent disease. No aneusomy for these chromosomes was detected in primary tumours from 20 patients with no detectable recurrence (P = 0.0082). The relative risk of recurrence was 3.62 times greater (95% confidence interval 1.6-8.1, Cox's multiple regression P = 0.0019) for patients with chromosomal aneusomy in primary TCC. Neither stage nor grade of the primary tumours was associated with recurrence in these patients, nor was there a significant association with increased grade (G2/3) or stage (greater than or equal to pT2) at recurrence. Conclusion These results suggest that the measurement of aneusomy by FISH, using markers for chromosomes 7 and 17, predict recurrence in a subgroup of patients with pTa/pT1 tumours at presentation. This finding may offer a new objective and quantitative test for patients destined to recur