- Email: [email protected]
Analysis of genetic alterations in normal bladder urothelium
LETTER TO THE EDITOR
Analysis of Genetic Alterations in Normal Bladder Urothelium TO THE EDITOR:
We read with particular interest the article by Junker et al.1 Using a cohort of 31 bladder specimens (16 cancers and 15 normal urothelium) utilizing microsatellite analysis (MSA) and comparative genomic hybridization (CGH), they demonstrated that bladder urothelium is not characterized by an overall genetic instability. Moreover, in their conclusions section, they suggested that these investigations should be completed by additional studies using other techniques such as sequencing of critical genes in bladder cancer or fluorescence in situ hybridization (FISH). In our previous investigation,2 we evaluated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and 51 tissue samples (proximal and distal) taken from macroscopically uninvolved urothelium surrounding tumors using the fluorescence in situ hybridization technique. On the basis of histologic evaluation, we divided the urothelium surrounding tumors in normal and pathologic mucosa and compared the mean percentages of aneusomic cells in chromosomes 1, 7, 9, and 17 in the three groups examined (tumor, proximal normal mucosa, and pathologic nonneoplastic proximal mucosa). Our results indicate that (a) a population of cells in morphologically normal epithelium possesses genetic aberrations common to those in bladder cancer and (b) there is no significant difference (P ⫽ NS) between tumor and surrounding pathologic epithelium regarding chromosome 7 and 9 aberrations. Our results demonstrate a close genetic relationship between all examined tumors and normalappearing mucosa. Cytogenetic findings show an accumulation of chromosomal aberrations during bladder cancer progression and a significant correlation with histopathologic classification (P ⫽ 0.001, r ⫽ 0.6). Our data, in agreement with that of Czerniak et al.3 confirm that alterations of chromosome 9 are associated with early events of urothelial morphologic changes and may even precede the development of macroscopic urothelial abnormalities. Moreover, according to Pycha et al,4 we demonstrated genetic instability of entire transitional epithelium by FISH. We do not agree with Dr. Junker’s view that “no general genetic instability is present.” In addition, we have a criticism about their results and comments after microsatellite analysis on chromosome 9. In our opinion, when there are alterations in 31% of normal urothelium adjacent to tumor, it is very brave to suggest that no genetic instability is present. In conclusion, it might be better to evaluate these results with a greater number of specimens and after performing a statistical analysis. © 2004 ELSEVIER INC. ALL RIGHTS RESERVED
REFERENCES 1. Junker K, Boerner D, Schulze W, et al: Analysis of genetic alterations in normal bladder urothelium. Urology 62: 1134 – 1138, 2003. 2. Cianciulli AM, Leonardo C, Guadagni F, et al: Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study. Hum Pathol 34: 214 –221, 2003. 3. Czerniak B, Chaturvedi V, Li L, et al: Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer. Oncogene 18: 1185–1196, 1999. 4. Pycha A, Mian C, Hofbauer J, et al: Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium. Urology 53: 92–97, 1999.
Costantino Leonardo Department of Urology “La Sapienza” University Rome, Italy
Michele Gallucci Department of Urology Regina Elena Cancer Institute Rome, Italy Anna Maria Cianciulli Department of Clinical Pathology Regina Elena Cancer Institute Rome, Italy doi:10.1016/j.urology.2004.01.054
REPLY BY THE AUTHORS: Leonardo and colleagues argue in their comments in favor of a general genetic instability of the entire urothelial lining in patients with bladder cancer. Although there are controversial results about the frequency of genetic changes in histologically inconspicuous urothelium in patients with bladder tumors, there are several lines of evidence supporting our view that in the majority of patients not the entire urothelial field is genetically altered. In our study, we showed that microsatellite alterations of chromosome 9 occurred in 31% of normal mucosa samples. These results are similar to data from a study of histologic-genetic mapping of cystectomy specimens by Stoehr et al.1 who found losses on chromosome 9 in 26% by microsatellite analysis. Furthermore, Obermann et al.2 detected losses on chromosome 9 in 21% of normal urothelial samples detected by 5-ALA fluorescence endoscopy using FISH. In contrast, there is a frequency of chromosome 9 deletions in urothelial hyperplasias, dysplasias, and carcinomata in situ of 50% to 80%.3– 6 The frequencies of genetic alterations reported in studies published by Cianciulli et al.7 and Pycha et al.8 who perUROLOGY 64: 405– 406, 2004 • 0090-4295/04/$30.00 405
Analysis of Genetic Alterations in Normal Bladder Urothelium TO THE EDITOR:
We read with particular interest the article by Junker et al.1 Using a cohort of 31 bladder specimens (16 cancers and 15 normal urothelium) utilizing microsatellite analysis (MSA) and comparative genomic hybridization (CGH), they demonstrated that bladder urothelium is not characterized by an overall genetic instability. Moreover, in their conclusions section, they suggested that these investigations should be completed by additional studies using other techniques such as sequencing of critical genes in bladder cancer or fluorescence in situ hybridization (FISH). In our previous investigation,2 we evaluated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and 51 tissue samples (proximal and distal) taken from macroscopically uninvolved urothelium surrounding tumors using the fluorescence in situ hybridization technique. On the basis of histologic evaluation, we divided the urothelium surrounding tumors in normal and pathologic mucosa and compared the mean percentages of aneusomic cells in chromosomes 1, 7, 9, and 17 in the three groups examined (tumor, proximal normal mucosa, and pathologic nonneoplastic proximal mucosa). Our results indicate that (a) a population of cells in morphologically normal epithelium possesses genetic aberrations common to those in bladder cancer and (b) there is no significant difference (P ⫽ NS) between tumor and surrounding pathologic epithelium regarding chromosome 7 and 9 aberrations. Our results demonstrate a close genetic relationship between all examined tumors and normalappearing mucosa. Cytogenetic findings show an accumulation of chromosomal aberrations during bladder cancer progression and a significant correlation with histopathologic classification (P ⫽ 0.001, r ⫽ 0.6). Our data, in agreement with that of Czerniak et al.3 confirm that alterations of chromosome 9 are associated with early events of urothelial morphologic changes and may even precede the development of macroscopic urothelial abnormalities. Moreover, according to Pycha et al,4 we demonstrated genetic instability of entire transitional epithelium by FISH. We do not agree with Dr. Junker’s view that “no general genetic instability is present.” In addition, we have a criticism about their results and comments after microsatellite analysis on chromosome 9. In our opinion, when there are alterations in 31% of normal urothelium adjacent to tumor, it is very brave to suggest that no genetic instability is present. In conclusion, it might be better to evaluate these results with a greater number of specimens and after performing a statistical analysis. © 2004 ELSEVIER INC. ALL RIGHTS RESERVED
REFERENCES 1. Junker K, Boerner D, Schulze W, et al: Analysis of genetic alterations in normal bladder urothelium. Urology 62: 1134 – 1138, 2003. 2. Cianciulli AM, Leonardo C, Guadagni F, et al: Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study. Hum Pathol 34: 214 –221, 2003. 3. Czerniak B, Chaturvedi V, Li L, et al: Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer. Oncogene 18: 1185–1196, 1999. 4. Pycha A, Mian C, Hofbauer J, et al: Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium. Urology 53: 92–97, 1999.
Costantino Leonardo Department of Urology “La Sapienza” University Rome, Italy
Michele Gallucci Department of Urology Regina Elena Cancer Institute Rome, Italy Anna Maria Cianciulli Department of Clinical Pathology Regina Elena Cancer Institute Rome, Italy doi:10.1016/j.urology.2004.01.054
REPLY BY THE AUTHORS: Leonardo and colleagues argue in their comments in favor of a general genetic instability of the entire urothelial lining in patients with bladder cancer. Although there are controversial results about the frequency of genetic changes in histologically inconspicuous urothelium in patients with bladder tumors, there are several lines of evidence supporting our view that in the majority of patients not the entire urothelial field is genetically altered. In our study, we showed that microsatellite alterations of chromosome 9 occurred in 31% of normal mucosa samples. These results are similar to data from a study of histologic-genetic mapping of cystectomy specimens by Stoehr et al.1 who found losses on chromosome 9 in 26% by microsatellite analysis. Furthermore, Obermann et al.2 detected losses on chromosome 9 in 21% of normal urothelial samples detected by 5-ALA fluorescence endoscopy using FISH. In contrast, there is a frequency of chromosome 9 deletions in urothelial hyperplasias, dysplasias, and carcinomata in situ of 50% to 80%.3– 6 The frequencies of genetic alterations reported in studies published by Cianciulli et al.7 and Pycha et al.8 who perUROLOGY 64: 405– 406, 2004 • 0090-4295/04/$30.00 405