Reduced CD151 expression is related to advanced tumour stage in urothelial bladder cancer.

AIMS: CD151 belongs to the group of tetraspanins and is aberrantly expressed in different tumours and differential expression has been associated with prognosis. The aim of this study was to clarify the relationship of CD151 expression with tumour phenotype and clinical outcome in bladder cancer. METHODS: A bladder cancer tissue microarray containing samples from 686 urothelial bladder cancers was analysed by immunohistochemistry. RESULTS: Membranous CD151 immunostaining was recorded in 409 (66.0%) of 620 analysable cases. High CD151 expression was seen in normal urothelium and in most non-invasive tumours. Low CD151 expression levels were associated with a more unfavourable tumour phenotype. CD151 staining was seen in 71.5% of 284 pTa, 62.1% of 145 pT1 and 60.4% of 187 pT2-4 cancers (p = 0.0033). CD151 staining was detectable in 77.3% of 75 grade 1, 71.1% of 273 grade 2 and 57.7% of 272 grade 3 cancers (p < 0.0001). CD151 expression status was not associated with overall or tumour-specific survival in muscle-invasive cancers (pT2-4), tumour progression in pT1 and recurrences in pTa tumours. CONCLUSION: On the basis of our data we conclude that loss of CD151 may contribute to bladder cancer progression through attenuation of cell adhesion. In clinically defined subgroups CD151 expression does not provide additional prognostic information.

Genomic deletion of PTEN is associated with tumor progression and early PSA recurrence in ERG fusion-positive and fusion-negative prostate cancer.

The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene is often altered in prostate cancer. To determine the prevalence and clinical significance of the different mechanisms of PTEN inactivation, we analyzed PTEN deletions in TMAs containing 4699 hormone-naïve and 57 hormone-refractory prostate cancers using fluorescence in situ hybridization analysis. PTEN mutations and methylation were analyzed in subsets of 149 and 34 tumors, respectively. PTEN deletions were present in 20.2% (458/2266) of prostate cancers, including 8.1% heterozygous and 12.1% homozygous deletions, and were linked to advanced tumor stage (P < 0.0001), high Gleason grade (P < 0.0001), presence of lymph node metastasis (P = 0.0002), hormone-refractory disease (P < 0.0001), presence of ERG gene fusion (P < 0.0001), and nuclear p53 accumulation (P < 0.0001). PTEN deletions were also associated with early prostate-specific antigen recurrence in univariate (P < 0.0001) and multivariate (P = 0.0158) analyses. The prognostic impact of PTEN deletion was seen in both ERG fusion-positive and ERG fusion-negative tumors. PTEN mutations were found in 4 (12.9%) of 31 cancers with heterozygous PTEN deletions but in only 1 (2%) of 59 cancers without PTEN deletion (P = 0.027). Aberrant PTEN promoter methylation was not detected in 34 tumors. The results of this study demonstrate that biallelic PTEN inactivation, by either homozygous deletion or deletion of one allele and mutation of the other, occurs in most PTEN-defective cancers and characterizes a particularly aggressive subset of metastatic and hormone-refractory prostate cancers.