Chromosomal Aberrations in Transitional Cell Carcinoma: Its Correlation with Tumor Behavior

Abstract

Objective: Fluorescence in situ hybridization (FISH) was used to study numerical aberrations of chromosomes 1, 3, 7, 9, 11, 15, 17, X and Y in interphase nuclei of 16 transitional cell carcinoma (TCC) cell lines of the urinary tract. The number of chromosomal signal copies was compared with the DNA ploidy and correlated with the cellular grading and original tumor staging. Methods: The single-target FISH with the repetitive DNA probes for chromosomes 1, 3, 5, 7, 9, 11, 15, 17, X and Y were performed in 16 human TCC cell lines. For each test specimen, a minimum of 200 nuclei were analyzed. The number of fluorescent signals per nucleus was recorded. Tumor ploidy was analyzed using the DNA propidium iodide flow cytometric method. These results were correlated with tumor grade and stage. Results: In two diploid TCC cell lines, on average 67% of detected chromosomes were di-(i)somic. In 14 aneuploid TCC cell lines, on average only 10% (0–44%) of detected chromosomes were di-(i)somic. Chromosome X was completely changed into polysomism in 16 TCC cell lines (native male:female ratio = 12:4) but was unrelated to tumor grade or stage. Chromosome Y was lost in 10 out of 12 (83%) TCC cell lines which originated from male patients but was unrelated to tumor grade or stage too. 31% of chromosomes 11 and 15 were disomic in 16 TCC cell lines, 38% of chromosome 3 was monosomic, and 81–88% (83 in average) of chromosomes 1, 7, 9, 17 were polysomic. Disomic chromosome 11 associated with lower grade TCC and disomic chromosome 15 associated with higher grade TCC were noted (p < 0.01). Higher incidence of low stage tumors was observed in TCC cell lines with disomic chromosome 11 or chromosome 15 (p < 0.01). There was no correlation in somatic status of chromosomes 1, 7, 9, 17 with tumor grade and stage. Conclusions: The results of the study demonstrate that polysomism of chromosomes 1, 7, 9, 17 and X occurs in most of the TCC cells with aneuploidy. The stability of chromosomes 11 and 15 is closely related to tumor grade and stage. The role of chromosome Y loss and monosomism of chromosome 3 in oncogenic relevant of bladder cancer is still unclear.