Chromosomal aberrations in benign and malignant bilharzia-associated bladder lesions analyzed by comparative genomic hybridization

Abstract

Background: Bilharzia-associated bladder cancer (BAC) is a major health problem in countries where urinary schistosomiasis is endemic. Characterization of the genetic alterations in this cancer might enhance our understanding of the pathogenic mechanisms of the disease but, in contrast to nonbilharzia bladder cancer, BAC has rarely been the object of such scrutiny. In the present study, we aimed to characterize chromosomal imbalances in benign and malignant post-bilharzial lesions, and to determine whether their unique etiology yields a distinct cytogenetic profile as compared to chemically induced bladder tumors.

Methods: DNAs from 20 archival paraffin-embedded post-bilharzial bladder lesions (6 benign and 14 malignant) obtained from Sudanese patients (12 males and 8 females) with a history of urinary bilharziasis were investigated for chromosomal imbalances using comparative genomic hybridization (CGH). Subsequent FISH analysis with pericentromeric probes was performed on paraffin sections of the same cases to confirm the CGH results.

Results: Seven of the 20 lesions (6 carcinomas and one granuloma) showed chromosomal imbalances varying from 1 to 6 changes. The most common chromosomal imbalances detected were losses of 1p21-31, 8p21-pter, and 9p and gain of 19p material, seen in three cases each, including the benign lesion.

Conclusion: Most of the detected imbalances have been repeatedly reported in non-bilharzial bladder carcinomas, suggesting that the cytogenetic profiles of chemical- and bilharzia-induced carcinomas are largely similar. However, loss of 9p seems to be more ubiquitous in BAC than in bladder cancer in industrialized countries.

Figure 1

Histologic section from invasive squamous cell carcinoma (case 217–98). Schistosoma haematobium eggs (arrows) embedded in bladder urothelium confirm the previous infestation with urinary schistosomiasis.

Figure 2

Histologic section from patient bladder with active urinary bilharziasis (case 286–98). Arrowheads indicate calcified bilharzial ova embedded in bladder urothelium.

Figure 3

The CGH profiles and FISH results in case 746–98. The CGH profiles of chromosomes 1 and 17 with thresholds 1.2 and 0.8 are shown in panel A. The CGH profiles of chromosomes 1 and 17 with thresholds 1.15 and 0.85 are shown in panel B. Two different cell populations are seen by FISH, shown in panel C. The centromere probes for chromosomes 1 and 17 were labeled by FITC and Rhodamine, respectively. Two signals of both probes are seen above and four signals of Icen and six signals of 17 cen are seen below.