In renal cell carcinoma the PTEN splice variant PTEN-Δ shows similar function as the tumor suppressor PTEN itself.

BACKGROUND: Loss of PTEN is involved in tumor progression of several tumor entities including renal cell carcinoma (RCC). During the translation process PTEN generates a number of splice variants, including PTEN-Δ. We analyzed the impact of PTEN-Δ in RCC progression. METHODS: In specimens of RCC patients the expression of PTEN-Δ and PTEN was quantified. The PTEN expressing RCC cell line A498 and the PTEN deficient 786-O cell line were stably transfected with the PTEN-Δ or PTEN transcript. In Caki-1 cells that highly express PTEN-Δ, this isoform was knocked down by siRNA. Cell migration, adhesion, apoptosis and signaling pathways activities were consequently analyzed in vitro. RESULTS: Patients with a higher PTEN-Δ expression had a longer lymph node metastasis free and overall survival. In RCC specimens, the PTEN-Δ expression correlated with the PTEN expression. PTEN-Δ as well as PTEN induced a reduced migration when using extracellular matrix (ECM) compounds as chemotaxins. This effect was confirmed by knockdown of PTEN-Δ, inducing an enhanced migration. Likewise a decreased adhesion on these ECM components could be shown in PTEN-Δ and PTEN transfected cells. The apoptosis rate was slightly increased by PTEN-Δ. In a phospho-kinase array and Western blot analyses a consequently reduced activity of AKT, p38 and JNK could be shown. CONCLUSIONS: We could show that the PTEN splice variant PTEN-Δ acts similar to PTEN in a tumor suppressive manner, suggesting synergistic effects of the two isoforms. The impact of PTEN-Δ in context of tumor progression should thus be taken into account when generating new therapeutic options targeting PTEN signaling in RCC.

Comparison of medical-grade and calibrated consumer-grade displays for diagnosis of subtle bone fissures.

OBJECTIVE: To compare the diagnostic accuracy of medical-grade and calibrated consumer-grade digital displays for the detection of subtle bone fissures. METHODS: Three experienced radiologists assessed 96 digital radiographs, 40 without and 56 with subtle bone fissures, for the presence or absence of fissures in various bones using one consumer-grade and two medical-grade displays calibrated according to the DICOM-Grayscale Standard Display Function. The reference standard was consensus reading. Subjective image quality was also assessed by the three readers. Statistical analysis was performed using receiver operating characteristic analysis and by calculating the sensitivity, specificity, and Youden's J for each combination of reader and display. Cohen's unweighted kappa was calculated to assess inter-rater agreement. Subjective image quality was compared using the Wilcoxon signed-rank test. RESULTS: No significant differences were found for the assessment of subjective image quality. Diagnostic performance was similar across all readers and displays, with Youden's J ranging from 0.443 to 0.661. The differences were influenced more by the reader than by the display used for the assessment. CONCLUSION: No significant differences were found between medical-grade and calibrated consumer-grade displays with regard to their diagnostic performance in assessing subtle bone fissures. Calibrated consumer-grade displays may be sufficient for most radiological examinations. KEY POINTS: • Diagnostic performance of calibrated consumer-grade displays is comparable to medical-grade displays. • There is no significant difference with regard to subjective image quality. • Use of calibrated consumer-grade displays could cut display costs by 60-80%.