DNA CYTOMETRY AND CHROMOSOME-9 ABERRATIONS BY FLUORESCENCE IN-SITU HYBRIDIZATION OF IRRIGATION SPECIMENS FROM BLADDER-CANCER PATIENTS

Objectives: To determine the sensitivity and specificity of combining fluorescence in situ hybridization (FISH) measurement of chromosome 9 and DNA cytometry of bladder irrigation specimens in the detection of bladder cancer. Methods: Bladder irrigation specimens were obtained fr om 57 normal control patients and 317 bladder cancer patients during c ystoscopic examinations. Bladder cancer patients were sampled in the a bsence of observable tumor (256 specimens) and concurrently with tumor (204 specimens). Chromosome 9 copy number was determined on a cellula r basis by FISH, and cellular DNA content was determined by Feulgen DN A staining and image cytometry. Results: Sensitivity of chromosome 9 F ISH was 42% for all tumors and was not correlated to transitional cell carcinoma tumor grade, while the sensitivity of DNA cytometry was 55% and improved with increasing grade from 38% for grade 1 to 90% for gr ade 5 tumors. The results of FISH and DNA cytometry were combined, res ulting in specificity of 92% and sensitivity of 69% for grade 1, 76% f or grade 2, and 97% for grade 3 tumors. Conclusions: The lack of incre ase with grade in the percentage of positive specimens by FISH support s the hypothesis that chromosome 9 aberrations are critical events in bladder tumorigenesis for many patients. These data demonstrate the pr esence of cells in irrigation specimens with specific genomic lesions of chromosome 9 and DNA content. Combining FISH on chromosome 9 and DN A cytometry provides an increase in sensitivity to transitional cell c arcinoma over either test alone. (C) 1998, Elsevier Science Inc. All r ights reserved.