The response of non–muscle-invasive bladder cancer (NMIBC) to intravesical immunotherapy with bacillus Calmette-Guérin (BCG) depends on adequate stimulation of an immune response. Although BCG has been used for decades, we lack tools to accurately predict response in individual patients. To address this deficiency, we initiated a clinical trial in patients with intermediate- and high-risk NMIBC. BCG was administered according to the Southwest Oncology Group protocol. Urine samples were collected for cytokine assay at baseline, immediately before and after BCG instillation at 6 wk, and immediately before and after the third BCG instillation of the first maintenance course. Levels of 12 cytokines were measured, and changes from baseline were calculated after treatment. A total of 130 patients were enrolled. Increases in single cytokines correlated with recurrence, but the best predictor of recurrence was changes in a combination of cytokines. A nomogram (CyPRIT) constructed using urinary levels of nine inducible cytokines (IL-2, IL-8, IL-6, IL-1ra, IL-10, IL-12[p70], IL-12[p40], TRAIL, and TNF-α) predicted the likelihood of recurrence with 85.5% accuracy (95% confidence interval 77.9–93.1%). This cytokine panel and nomogram have potential for identifying patients at risk of tumor recurrence during BCG treatment to guide modification of the dose and duration of BCG immunotherapy.

NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

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BACKGROUND The nuclear protein B23, nucleophosmin, is an RNA‐associated nucleolar phosphoprotein reported to be more abundant in malignant and growing cells than in normal nondividing cells. We examined the levels of B23 in fresh human prostate tissue and in five human prostate cancer cell lines with monoclonal antibodies (mAb) to nucleophosmin (α‐B23) and to human prostate cancer nuclear matrix proteins (PRO:4‐216). METHODS mAb PRO:4‐216 and mAb α‐B23 were used for protein level detection. Nuclear matrix proteins (NMPs) were prepared from prostate tumor and five human prostate cancer cell lines: LNCaP, TSU, DU145, PC‐3, and PPC‐1. The NMPs were run on one‐dimensional and two‐dimensional (2D) electrophoresis gels for Western blot analysis with the two mAbs. Histologic sections from paraffin‐embedded normal and cancerous prostate tissue were stained immunohistochemically with both mAbs. RESULTS PRO:4‐216 and B23 mAbs identified a 40‐kD protein (pI ∼5.0) by Western blot analysis in the human prostate cancer cell lines and on two‐dimensional blots of human prostate cancer NMPs. Immunohistochemical staining demonstrated large punctate nuclear dots in most cancer nuclei, while staining of normal tissue was less intense or absent. Predominant reactivity was of epithelial nuclei, with some minor reactivity of stromal nuclei. Red blood cells (RBCs) and white blood cells (WBCs) were routinely negative. CONCLUSIONS PRO:4‐216, previously characterized as recognizing prostate cancer nuclear matrix proteins, recognized B23/nucleophosmin. PRO:4‐216 and α‐B23 showed intense immunohistochemical staining of B23/nucleophosmin in cancer nuclei compared to adjacent normal cells in paraffin‐embedded prostate tissue. This preliminary study showed the potential of B23 as a tumor marker for human prostate cancer. Prostate 39:298–304, 1999. © 1999 Wiley‐Liss, Inc.

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NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.

NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.