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Tissue microarrays (TMAs) provide results similar to those obtained by standard methods and permits rapid profiling of molecular tumor markers. We evaluated the expression of pAkt, PTEN, and L-Plastin on a TMA of transitional cell carcinoma (TCC) of the bladder to determine the significance of these proteins in the progression of bladder cancer. Akt, a serine/threonine kinase, is a major downstream target of PI-3 kinase and is important in regulating key processes that are relevant for tumor growth and progression, i.e. cell-cycle progression, survival, angiogenesis, motility, and invasion. IHC evaluations of human tumors have found that phosphorylated Akt (pAkt) is strongly expressed in advanced prostate, breast and ovarian cancers. PTEN is a tumor-suppressor gene and encodes a phosphatase upstream of AKT in the PI (phosphatidylinositol)-3 kinase pathway. Recent studies indicate that PTEN is mutated or deleted in 14-23% of invasive bladder cancers. L-plastin is an actin-bundling protein that is abundantly expressed in hemopoietic cell lineages, and is overexpressed in many types of solid malignancies in humans. It has been suggested to be a potential biomarker for metastasis. We performed IHC staining of a TMA consisting of 251 bladder TCCs usingantibodies to pAkt, PTEN, and L-plastin. Four groups of TCC tumor types were examined: nonpapillary invasive grade (G) 3, papillary invasive G3, papillary noninvasive G3, and papillary noninvasive G2. The slides were scanned and analyzed using Applied Images automated system and software. We identified L-plastin as a potentially important gene in bladder TCC through gene expression profiling. All 4 of the tumor groups expressed PTEN and L-plastin. However, the papillary noninvasive tumors expressed significantly higher L-Plastin when compared to the nonpapillary invasive G3 tumors (p<0.01). Nonpapillary invasive tumors had lower cytoplasmic and nuclear PTEN expression (p<0.04) compared to all the other tumor groups. Significantly higher expression of pAkt was found in papillary noninvasive G2 tumors than in nonpapillary invasive G3 tumors (p<0.01). Our analysis also identified a moderate correlation between pAkt and L-plastin expression (Spearman correlation coefficient = 0.49, p<0.01). In summary, TMA analysis demonstrated that pAkt, cytoplasmic PTEN, and L-plastin expression are higher in papillary noninvasive bladder tumors than in non-papillary invasive bladder tumors. The expression of pAkt, PTEN, and L-plastin are altered in bladder cancer suggesting that these molecules play an important role in the progression of this disease. “Supported by National Institutes of Health SPORE grant P50 CA91846 and National Institutes Health Core Grant CA16672.”

[Proc Amer Assoc Cancer Res, Volume 46, 2005]