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Centromeric Copy Number of Chromosome 7 Is Strongly Correlated with Tumor Grade and Labeling Index in Human Bladder Cancer¹

Departments of Laboratory Medicine [F. M. W., F. G. F., B. H. M.], Pathology [R. K., M. B. C.], and Urology [P. R. C.], University of California San Francisco, San Francisco, California 94143-0808

The relationship between interphase cytogenetics and tumor grade, stage, and proliferative activity was investigated in 27 transitional cell carcinomas of the urinary bladder. Using fluorescence in situ hybridization with chromosome-specific DNA probes, the copy number of pericentromeric sequences on chromosomes 7, 9, and 11 was detected within interphase nuclei in touch preparations from tumor biopsies. Monosomy of chromosome 9 was detected in 9 of 22 cases (41%), while tetrasomy for chromosomes 7 and 11 was detected in 10 of 26 (38%) and 6 of 23 (26%) cases, respectively. Copy number of chromosome 7 was the most highly correlated with increasing tumor grade (r² = 0.616, P < 0.001, Spearman rank correlation) or increasing pathological stage (r² = 0.356, P < 0.002). Copy number for chromosome 9 did not correlate with either grade or stage (P > 0.05). Tumor labeling index (LI) was determined after in vitro 5-bromodeoxyuridine incorporation, while proliferating cell nuclear antigen LI was determined immunohistochemically. Increasing LI by either method correlated with increasing copy number for all three chromosomes tested (r² = 0.473, P < 0.002 for 7; r² = 0.384, P < 0.01 for 11; and r² = 0.316, P < 0.05 for 9). Since high tumor grade, stage, and LI are all indicative of more aggressive tumor behavior and worse prognosis, these findings suggest that polysomy, especially for chromosome 7, may be highly predictive for bladder tumor aggressiveness.

¹ This work was supported by NIH Grant CA47537, as part of the Bladder Marker Network of the National Cancer Institute.

² To whom requests for reprints should be addressed, at Laboratory for Cell Analysis, MCB 232, Dept. of Laboratory Medicine, University of California San Francisco, San Francisco, CA 94143-0808.

³ Present Address: Department of Pathology, University of Iowa, Iowa City, IA.

Received 12/ 7/90. Accepted 5/ 7/91.

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