Bladder cancer can be viewed as a prototype for carcinogen-induced neoplasia. This has been demonstrated experimentally in a variety of systems and in man through epidemiological studies of occupational exposure to putative carcinogens. The natural history of this neoplasm demonstrates recurrence in time and space, i.e., multifocal disease. This clinical scenario is precisely what would be expected if a target tissue, e.g., urothelium, was continuously exposed to a weak carcinogen. The detection of gross disease is clinically easy. However, the ability to intervene at early stages and monitor the success of this treatment requires the definition of early markers for bladder cancer. Integrins are a family of cell surface proteins, many of which function as receptors for extracellular matrix components. Normal epithelial cells express the integrin alpha6beta4 in association with an anchoring structure known as the hemidesmosome. Urothelium expresses alpha6beta4 on the basal layer of cells similar to the distribution seen on other epithelial surfaces. Even early stages of bladder cancer demonstrate an alteration in the expression of this integrin. Low-stage bladder tumors express alpha6beta4 diffusely throughout the tumor as well as at the invading margin. Altered expression of alpha6beta4 may be an early marker for bladder cancer which may contribute to an invasive phenotype. A second potential marker is detected by DD23, an IgG1 murine monoclonal antibody triggered by the immunization of a BALB/c mouse with a fresh human bladder tumor specimen. The antigen detected by DD23 is not present on normal urothelial specimens. It is expressed on 81% of bladder tumors tested and is present on both low-grade, non-invasive and high-grade, invasive tumors. Although no normal bladder or ureteral tissues were DD23-positive, two of five histologically normal bladder areas from patients who had radical cystectomies for bladder cancer expressed the DD23 antigen. The significance of this finding has not yet been completely evaluated; however, it may represent an early neoplastic change prior to obvious histologic abnormality. Antigens associated with bladder cancer may be helpful in the early detection of bladder cancer and in providing markers useful in future chemoprevention trials.
