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Background. The current study was initiated to investigate measurable objective and reproducible characteristics that might have prognostic significance in bladder cancer. Methods. Tumor samples from 91 patients with primary transitional cell carcinoma (TCC) of the urinary bladder were studied by DNA image cytometry and cytogenetic analysis. Image cytometry is a more sensitive method of determining ploidy than flow cytometry, especially in tumors with a low number of aneuploid cells. Results. There was a significant difference in survival between DNA image cytometry-determined diploid and nondiploid cases. The presence of nuclei with a high DNA content indicated poor prognosis. The 2C deviation index (2CDI) also was an indicator of survival. Image cytometry-determined factors also were found to be strong predictors of progression-free survival. In multivariate analysis, 2CDI was the only cytometric parameter with an independent but weak correlation with survival. In multivariate analysis, none of the cytometric parameters had an important contribution to prediction of progression-free survival. In superficial tumors (Ta and T1), 2CDI appeared to be the most important independent predictor of survival. With respect to progression-free survival, tumors with a high mitotic index proved to have a worse prognosis. Conclusions. Parameters determined by DNA image cytometry appear to be valuable in predicting survival and progression-free survival and may be useful in addition to the classic parameters of stage and grade, especially in superficial TCC.

The invasion of surrounding tissue by a developing carcinoma is an important event in the development of cancer, and survival statistics confirm that if a cancer is surgically removed prior to invasion the prognosis is more favorable. During the process of invasion, carcinoma cells secrete enzymes that attack protein components of the basement membrane, which would otherwise act as a protective barrier under an epithelial cancer. In the past, it has been difficult to directly visualize this process under the microscope, as there were no specific stains to selectively dye the basement membrane. However, the availability of antibodies to the protein components of basement membrane now makes such visualization practical. An investigation was undertaken to characterize the changes that occur in the basement membrane during cancer invasion and to determine if these changes may be of prognostic value. Using immunological methods, researchers examined the basement membrane of 125 surgical specimens of bladder cancer. While the researchers anticipated that the basement membrane would be intact in noninvasive cancers and destroyed in regions of invasion, examination of the microscopic slides revealed that the true situation is more complicated. Basement membrane is not absent in regions of cancer invasion, which probably reflects the fact that basement membrane is not a static entity, but rather a dynamic substance that is being laid down by reactive cells even as it is being enzymatically destroyed by the invading cancer cells. However, it was possible to show that areas of absent or patchy basement membrane correlated well with the stage of the cancer. Furthermore, it was found that survival was better among patients with intact basement membrane than among those in whom the patchy or absent areas could be seen. However, analysis showed that the correlation between survival and cancer stage is strong, and beyond being a marker for stage, the information about basement membrane did not provide any useful prognostic information. The authors point out, though, that when the stage of the tumor is ambiguous, immunohistochemical staining with basement membrane antibodies may provide a useful microscopic technique. (Consumer Summary produced by Reliance Medical Information, Inc.)

We compared the distribution of DNA synthesis over the arterial tree of young normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with marginally elevated blood pressure. Six-week-old male SHR and WKY rats were therefore infused with 5-bromo-2'-deoxyuridine (BrdUrd) for 2 days and the nuclear incorporation of the thymidine analogue in the media of various arteries was determined by immunohistochemistry. In WKY rats, 2.5 of the arterial smooth muscle nuclei in elastic, muscular and resistance arteries incorporated BrdUrd. In SHR, DNA synthesis was more marked in large arteries than in resistance arteries. It was in addition significantly larger in the aorta, superior mesenteric, renal and femoral arteries of the SHR than in those of the WKY rats. However, nuclear incorporation of BrdUrd in vivo did not differ between SHR and WKY rats in aortic endothelium, carotid arterial smooth muscle, nor in mesenteric or renal resistance arteries. Between 6 and 20 weeks of age, the number of nuclear profiles per media cross-section did not increase in large arteries of WKY rats and SHR. During this period of time, however, carotid artery and thoracic aorta weight and DNA content increased. SHR large arteries gained more DNA than those of WKY rats. These data indicate that DNA synthesis is uniformly distributed over the arterial system in young WKY rats and that DNA synthesis is elevated in the smooth muscle of large arteries of 6-week-old SHR but not in their resistance arteries.