In the category of urogenital carcinomas, the number of persons who are affected with urothelial carcinoma (such as bladder carcinoma or renal pelvic and ureteral carcinoma) is the second only to those suffering from prostate carcinoma. In Japan, in a single year, 7,886 males and 2,697 females are affected with bladder carcinoma (1994, Foundation for Promotion of Cancer Research). The number of persons dying therefrom is 2,856 males and 1,277 females (1997, same as above). This carcinoma is the fifth most common among all types of carcinomas in the United States. Since approximately 70% of these patients experience repeat carcinoma recurrence in their urinary tracts, the number of patients is deduced to be constantly as large as several tens of thousands in Japan alone, including examples of follow-up cases. In physical examinations, erythrocyturia presenting 5 or more blood erythrocytes per visual field is observed in about 3% of general males and about 7% of general females. Accordingly, the number of persons to be subjected to screening for urothelial carcinoma is enormous. In general, cystoscopy is a decisive factor for the confirmed diagnosis. However, it is unsuitable for mass screening since this process is invasive and expensive. Thus, there was an urgent need to develop a diagnostic technique that is noninvasive, capable of dealing with a large number of specimens, and excellent in sensitivity and specificity. Urine cytology is a representative noninvasive examination, which has the longest history of clinical application. While this technique is excellent in specificity (95% to 100%), its sensitivity is low (40% to 60%). Sensitivity thereof is particularly deficient when examining well-differentiated carcinoma (0% to 15%). The sensitivity of auxiliary diagnosis using a bladder tumor antigen (BTA), Nuclear Matrix Protein 22 (NMP22), or the like, which has been recently put to practical use, is reported to be somewhat improved compared with that of cytodiagnosis of urine. The auxiliary diagnosis, however, are likely to indicate false-positive for gross hematuria or cystitis. Because of this low specificity, it has not yet resulted in a status exceeding that of urine cytology.
In the field of cancer research, however, expression of a protein referred to as a calreticulin protein is found to be enhanced in, for example, hepatocellular carcinoma (see Yoon G S. et al., Cancer Res, 60: 1117-1120, 2000 and Yu L R, et al., Electrophoresis, 21: 3058-3068, 2000) or breast carcinoma (see Bini L. et al., Electrophoresis, 18: 2832-2841, 1997). A calreticulin protein is only reported as a spot exhibiting enhanced expression appeared in the proteome analysis with respect to urothelial carcinoma (see Celis A. et al., electrophoresis, 20: 300-309, 1999). It has not yet been examined as a tumor marker for urothelial carcinoma.