Prostate cancer biology varies from locally confined tumors with low risk for relapse to tumors with high risk for progression even after radical prostatectomy. Currently, there are no reliable biomarkers to predict tumor relapse and poor clinical outcome. In this study, we correlated expression patterns of the androgen receptor (AR) coactivators lysinespecific histone demethylase 1 (LSD1) and four and a half LIM-domain protein 2 (FHL2), AR, Gleason score, Gleason grade, and p53 expression in clinically organ confined prostate cancers with relapse after radical prostatectomy. Our data reveal that high levels of LSD1, nuclear expression of the FHL2 coactivator, high Gleason score and grade, and very strong staining of nuclear p53 correlate significantly with relapse during follow-up. No correlation exists with relapse and the expression of AR and cytoplasmic expression of FHL2. To confirm these data, we did quantitative reverse transcription-PCR and Western blot analyses in a subset of tumor specimens. Consistently, both LSD1 mRNA and protein levels were significantly up-regulated in high-risk tumors. We previously identified LSD1 and FHL2 as nuclear cofactors interacting specifically with the AR in prostate cells and showed that both stimulate androgen-dependent gene transcription. Our present study suggests that LSD1 and nuclear FHL2 may serve as novel biomarkers predictive for prostate cancer with aggressive biology and point to a role of LSD1 and FHL2 in constitutive activation of AR-mediated growth signals. (Cancer Res 2006; 66(23): 11341-7)
SPECT/CT significantly improved the specificity and positive predictive value of bone scintigraphy in cancer patients. In breast cancer patients, we found a slight increase in sensitivity. SPECT/CT had a significant effect on clinical management because of correct downstaging and upstaging, better definition of the extent of metastases, and a reduction in further diagnostic procedures.
Objectives• To identify the prognostic impact of venous tumour thrombus (VTT) in locally advanced renal cell carcinomas (RCCs).• To further differentiate the clinical course of patients with VTT who have similar clinicopathological characteristics.
Patients and Methods• We determined the VTT consistency (solid vs friable) in a retrospective cohort of 200 patients with RCC who had undergone nephrectomy between 1994 and 2011.• We examined the correlation of VTT consistency in these patients with clinical and pathological variables.
Results• A total of 65% of the patients had solid VTT and 35% had friable VTT, which has a significantly lower amount of cell-cell adhesion molecules and connective tissue than solid VTT.• We found that friable VTT was associated with advanced pT stage, higher VTT level, papillary RCC subtype and a lower age.• Patients with friable VTT had a significantly shorter median overall survival than those with solid VTT (29 vs 89 months), but VTT consistency was not found to be an independent predictor of patients' survival in the multivariate Cox analysis.• We found that VTT consistency was an independent significant predictor of overall survival in patients without evidence of distant and nodal metastases (N = 119).
Conclusions• The VTT consistency is caused by the tumour and not by different surgical handling. • Friable VTT is an important adverse prognostic predictor of overall survival in patients with non-metastatic RCC.
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