Prostate cancer has become one of the most common malignancies worldwide. Although lacking in specificity its diagnosis is still based partially on the serumbased test for prostate-specific antigen. As its pathogenesis has not yet been deciphered, the ongoing search for new and more reliable biomarkers remains a challenge to stratify disease onset and progression. Matrix-assisted laser desorption/ ionization (MALDI)-Imaging is a promising technique to assist in this endeavor. It delivers accurate mass spectrometric information of the sample's proteins and enables the visualization of the spatial distribution of protein expression profiles and correlation of the information with the histomorphological features of the same tissue section. This study describes the analysis of 22 prostate sections (11 with and 11 without prostate cancer) by MALDI-Imaging. Specific protein expression patterns were obtained for normal and cancerous regions within the tissue sections. Applying a 'support vector machine' algorithm to classify the cancerous from the noncancerous regions, an overall cross-validation, a sensitivity and specificity of 88, 85.21 and 90.74%, respectively, was achieved. Additionally four distinctively overexpressed peaks were identified: 2,753 and 6,704 Da for non-cancerous glands, and 4,964 and 5,002 Da for cancerous glands. The results of this first clinical study utilizing the new technique of MALDI-Imaging underline its vast potential to identify candidates for more reliable prostate cancer tumor markers and to enlighten the pathogenesis of prostate cancer.

Many molecular alterations are known to occur in urothelial carcinoma of the bladder, but their significance for tumor progression is poorly understood. Deletions of chromosome 8p are frequently found in several tumor types and are often associated with progressive disease. In all, 99 bladder tumors were screened for deletions at 8p using loss of heterozygosity (LOH) and multicolor fluorescence in situ hybridization FISH analyses. Allelic loss on chromosome 8p in at least one marker was found in 25/99 (25%) tumors. There was a significant correlation of 8p deletions with invasive tumor growth and a highly significant association with papillary growth pattern in patients with invasive disease. cDNA array analyses revealed that secreted Frizzled-related protein 1 (sFRP1), an antagonist of Frizzled receptors and Wnt pathway activation on chromosome 8p12-11.1, is frequently downregulated in bladder cancer. To investigate sFRP1 as a candidate for a putative progressionrelated gene on 8p, urothelial cell lines and primary urothelial carcinomas were screened for sFRP1 expression using quantitative real-time PCR, Northern blot, immunofluorescence and immunohistochemistry (IHC). Of the investigated bladder cancers, 38% showed loss of sFRP1 expression by quantitative RT-PCR. Evaluation of the protein expression by IHC using tissue microarrays containing 776 bladder cancers revealed loss or strong reduction of sFRP1 expression in 66% of cases. SFRP1 loss was associated with higher tumor stage and grade and shorter overall survival. In addition, loss of sFRP1 was an independent indicator of poor survival in patients with papillary but not with muscle invasive bladder cancer. There were neither mutations in the coding region of sFRP1 nor homozygous deletions at 8p12-11.21. However, promoter methylation was detected using methylation-specific PCR in 29% of cases. In conclusion, we could show a close correlation of chromosome 8p deletions and progression of papillary bladder tumors. The sFRP1 gene on chromosome 8p12-11.1 could be a candidate gene for the predicted, progression-related tumor suppressor gene in bladder cancer and could contribute to urothelial carcinogenesis.

5-Aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) fluorescence has been shown to have high tumor cell selectivity in various organs, including the gastrointestinal (GI) tract. To better understand and to possibly find new approaches to therapeutic application, we investigated the uptake kinetics and consequent metabolism of ALA and PPIX, respectively. Three colon carcinoma (CaCo2, HT29, SW480) and a stromal cell line (fibroblast, CCD18) were chosen to mimic important aspects of malignant mucosa of the GI tract. Because differential PPIX concentrations in these cell lines represented the in vivo observations (ratio tumor vs normal 10:1-20:1), we analyzed the ALA uptake, mitochondrial properties and key molecules of PPIX metabolism (porphobilinogen deaminase [PBGD], ferrochelatase [FC], iron content, transferrin receptor content). The tumor-preferential PPIX accumulation is strongly influenced, but not solely determined, by activity differences between the PPIX-producing PBGD and the PPIX-converting FC, when compared with fibroblasts. Tumor-specific PPIX accumulation is generated by ALA conversion rather than by initial ALA uptake because no significant overall difference in uptake (about 0.6 microg ALA/mg protein) of ALA is seen. In conclusion, further research of tumor cell selectivity of PPIX fluorescence should focus on the mechanisms responsible for an altered PPIX metabolism to find tumor-specific target molecules, thus leading to an improved clinical practicability of ALA application and consequent endoscopy.

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