The CancerWeb Report, What's New In Cancer: June, 1996
Bladder Cancer

• A new indicator for outcome in bladder cancer? - In a short report in the June 1, 1996 issue of Cancer Research, doctors at the University of Oxford in the UK describe a potential new indicator of which patients with bladder cancer are likely to have a poor clinical outcome. They measured a factor, called midkine (MK), which stimulates the growth of new blood vessels. This process, called angiogenesis, is essential if tumors and their metastases are to receive the blood supply needed for their growth. They found evidence of MK factor in 46 of 47 tumor samples, and in 5 of 7 normal bladder specimens, but levels of MK averaged four times higher in tumors than in normal tissue, with eight tumors showing ten-fold increases. Among 22 patients with invasive bladder cancer, seven were alive at one year with no evidence of tumor; in five of these MK was at normal levels at diagnosis. In contrast, of the 15 patients who died, only two had normal MK expression, the others having levels that averaged three times normal. Overexpression of MK may be a useful new indicator of prognosis. (O'Brien, Cancer Research 56:2515, 1996)

  Editor's Comment: - Angiogenesis is receiving much attention recently as an indicator of prognosis. Tumors must have a blood supply in order to grow, otherwise they remain small, and probably eventually die off. Most studies on this topic, see for example Cancer Web Report, volume 2, number 2, February 1996 (colorectal cancer and neuroblastoma), and volume 2, number 6, June, 1996 (stomach cancer), have measured the actual number of tiny blood vessels, so-called microvessels, in the tumor specimens. However, formation of these vessels is stimulated by the angiogenesis factors that the tumors produce, so the research in this article used one of these factors as an alternative index of blood vessel formation that is probably easier to measure.

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• p53 gene mutations and high-risk bladder cancer - In a report in the June, 1996 issue of Clinical Cancer Research, doctors at the University of Nijmegen in the Netherlands found a relationship between progression of high-risk bladder cancer and the presence of mutations in the p53 tumor-suppressor gene of cells in their bladder washings. Such bladder washings contain cells, including cancer cells shed from the bladder surface. The p53 gene normally regulates the rate at which cells enter their cell cycle, so controlling growth rates. Among 26 patients selected as being at high risk for progressing from local to invasive disease, six of 13 who did progress had p53 mutations compared with only one of the 13 whose disease did not progress. The test had the advantage of disclosing propensity to progression an average eight months before it occurred, allowing changes in treatment to be made to prevent invasive disease. However, the main disadvantage is the large percentage having a negative test who still progressed. This means that treatment decisions will still require the use of additional markers and clinical indicators. (Vet, Clin Cancer Res 2:1055, 1996)

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• Telomerase and bladder cancer - We described in Volume 1 issue 3 (November, 1995; under "Carcinogenesis") of the Cancer Web Report that the ends of normal chromosomes have a tendency to "fray" during DNA synthesis, and they have "caps" (called telomeres) at their ends to help protect them from this shortening and resulting loss of information. Unfortunately, the caps themselves gradually shorten until they can no longer carry out their function. An enzyme, telomerase, found in tumors and embryonic, but not most normal tissues, can prevent this damage by repairing the telomeres. In that report this enzyme was found in human stomach cancer. This month, another Japanese group, from Yokohama, found the enzyme in 39 of 40 bladder tumor specimens (only one early-stage sample lacked it), in one of two samples of abnormal (so-called dysplastic) bladder tissue, but in no normal bladder specimens. The enzyme level increased as the cancer became more advanced and invasive. (Lin, Clin Cancer Res 2:929, 1996)

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• A predictor for response to BCG? - Superficial bladder cancer is highly responsive to bacillus Calmette-Guerin - BCG - which is applied directly into the bladder, and produces a cellular immune response. Remission rates are around 70%. Is it possible to predict which tumors will respond? The answer from researchers at the Hebrew University-Hadassah Medical School in Israel is yes. They found that a necessary factor in obtaining a response to BCG is induction of expression of the interleukin-2 gene. Of 23 patients with resistant or persistent disease, 22 showed no induction compared with 35 of 50 patients who had gone into remission. Specificity was higher at 86% for very limited, so- called in situ cancer. There was no relationship with induction of interferon. (Kaempfer, J Clin Oncol 14:1778, 1996)