July 2002

From Journal of the National Cancer Institute

Other highlights in the July 17 issue of JNCI

Elevated Protein Levels May Be a Diagnostic Marker for Bladder Cancer
A new study suggests that testing urine for elevated levels of a protein involved in the initiation of DNA replication may be a tool to detect bladder cancer. The results appear in the July 17 issue of the Journal of the National Cancer Institute.

The gold standard test for diagnosing bladder cancer is cystoscopy, or an examination of the bladder through a cystoscope that is inserted into the body through the urethra. However, the test is invasive and costly, and the symptoms of bladder cancer (blood in the urine and pain when urinating) that could prompt cystoscopy can also indicate the presence of a less serious condition. A simple urine test, called urine cytology, to detect the presence of abnormal cells in the urine is also used to diagnose bladder cancer; however, the test has low sensitivity (the ability to detect disease in people who actually have the disease).

The minichromosome maintenance (Mcm) family of proteins plays a critical role in regulating the initiation of DNA replication. Previous studies have suggested that expression of these proteins is a marker of epithelial carcinogenesis.

Kai Stoeber, M.D., of the University of Cambridge, Gareth Williams, Ph.D., of University College London, and colleagues tested whether measuring Mcm5 levels in urine could detect the presence of bladder cancer. They tested the urine of 353 patients with urinary tract symptoms or urothelial neoplasia who were going to have cystoscopies. They found that the Mcm5 test had a higher sensitivity (i.e., was more likely to yield a positive result in people who actually have bladder cancer) than urine cytology. They also found that patients with prostate cancer had higher levels of Mcm5 in their urine than men without prostate cancer, although the authors caution that this observation was based on a small number of patients.

Also in the July 17 JNCI:

  • DNA Repair Capacity and Non-Small Cell Lung Cancer:
    Non-small cell lung cancer (NSCLC) is frequently resistant to chemotherapy drugs. This resistance has been associated with elevated nucleotide excision repair (NER) in tumor tissue. Carol H. Bosken, M.D., Margaret R. Spitz, M.D., and colleagues from the University of Texas M. D. Anderson Cancer Center tested the hypothesis that patients with effective DNA repair capacity (DRC), an estimate of NER activity, would have poorer survival than patients with suboptimal DRC, and that the association between DRC effectiveness and survival would be most marked in patients receiving chemotherapy. A retrospective analysis of DRC in 375 NSCLC patients found that for every unit (%) increase in DRC, the risk for death increased by approximately 5%. In a subset of 86 patients treated with chemotherapy only, the risk for death increased by 11%. The authors conclude that effective DRC may be a risk factor for poorer survival in NSCLC patients treated with chemotherapy.

  • Insulin-Like Growth Factor I Pathway and Prostate Cancer:
    To determine whether plasma levels of insulin-like growth factor I (IGF-I) and its binding protein IGFBP-3 predict more aggressive forms of prostate cancer, June M. Chan, Sc.D., of the University of California at San Francisco, and colleagues investigated the association between plasma levels of each with specific stages and grades of prostate cancer in a prospective case-control study. They found that plasma levels of IGF-I and IGFBP-3 were predictors of advanced-stage prostate cancer but not of early-stage cancer. Combining these measurements with a standard prostate-specific antigen (PSA) test increased the specificity (correct identification of patients without prostate cancer) but decreased the sensitivity for detecting patients with prostate cancer compared with a PSA test alone. The authors conclude that levels of IGF-I and IGFBP-3 may predict the risk of developing advanced-stage prostate cancer, but their utility for identifying patients with incident cancer may be limited.

  • Expression of Glucose Transporter 1 and Matrix Metalloproteinase-2 in Human Cancers:
    Cancer cells express higher levels of glucose transporter proteins (Gluts) than normal cells. Glut-1 overexpression is associated with increased cell invasiveness. Matrix metalloproteinase-2 (MMP-2) is also overexpressed in cancer cells and is associated with invasiveness. Satoshi Ito and Shunichiro Kubota, M.D., of the University of Tokyo, and colleagues tested the hypothesis that Glut-1 may regulate MMP-2 expression. They transfected Glut-1 cDNA or Glut-1 antisense oligonucleotides in a human rhabdomyosarcoma cell line and analyzed MMP-2 mRNA expression and cell invasiveness. The authors found that changes in MMP-2 expression were positively associated with changes in Glut-1 expression. For example, increased Glut-1 expression was associated with increased MMP-2 expression and increased invasiveness, and suppression of Glut-1 expression was associated with decreased MMP-2 expression and invasiveness. The authors noted that this association between Glut-1 and MMP-2 expression was also tightly associated in human cancer cell lines and cancer tissues. The authors conclude that Glut-1 could be a potential target for therapy of various cancers that overexpress Glut-1.

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