This study examines the clinical impact of PTEN genomic deletions using fluorescence in situ hybridisation (FISH) analysis of 107 prostate cancers, with follow-up information covering a period of up to 10 years. Tissue microarray analysis using interphase FISH indicated that hemizygous PTEN losses were present in 42/107 (39%) of prostatic adenocarcinomas, with a homozygous PTEN deletion observed in 5/107 (5%) tumours. FISH analysis using closely linked probes centromeric and telomeric to the PTEN indicated that subband microdeletions accounted for B70% genomic losses. Kaplan -Meier survival analysis of PTEN genomic losses (hemizygous and homozygous deletion vs not deleted) identified subgroups with different prognosis based on their time to biochemical relapse after surgery, and demonstrated significant association between PTEN deletion and an earlier onset of disease recurrence (as determined by prostate-specific antigen levels). Homozygous PTEN deletion was associated with a much earlier onset of biochemical recurrence (P ¼ 0.002). Furthermore, PTEN loss at the time of prostatectomy correlated with clinical parameters of more advanced disease, such as extraprostatic extension and seminal vesicle invasion. Collectively, our data indicates that haploinsufficiency or PTEN genomic loss is an indicator of more advanced disease at surgery, and is predictive of a shorter time to biochemical recurrence of disease.

TMPRSS2:ERG gene fusions and PTEN deletions are the most common genomic aberrations in prostate cancer. Recent work has suggested that the TMPRSS2:ERG fusion is associated with a more aggressive phenotype. Similarly, PTEN deletion has been associated with biochemical recurrence and lymph node metastasis. To date, there has been no systematic analysis of the combined influence of genomic PTEN deletion with TMPRSS2:ERG gene fusions on clinical parameters of prostate cancer progression. We carried out a retrospective analysis of 125 prostate cancers with known clinical outcome using interphase fluorescence in situ hybridization to detect the relative prevalence of TMPRSS2:ERG rearrangements and/or PTEN genomic deletions. TMPRSS2:ERG rearrangement was found in 60 of 125 (48%) prostate cancers. Duplication of TMPRSS2:ERG fusion was observed in seven (6%) tumors. Gleason grade (P ¼ 0.0002)/score (P ¼ 0.001), median tumor volume (P ¼ 0.0024), preoperative PSA (P ¼ 0.001) and perineural invasion (P ¼ 0.0304) were significantly associated with biochemical recurrence by univariate analysis with TMPRSS2:ERG approaching significance (P ¼ 0.0523). By multivariate analysis, relevant factors associated with recurrence were Gleason scores 7 (P ¼ 0.001) and 8-10 (P ¼ 0.015), PTEN homozygous deletion (P ¼ 0.013) and concurrent TMPRSS2:ERG fusion and PTEN deletion (P ¼ 0.036). Kaplan-Meier analysis indicated that the presence of TMPRSS2:ERG fusion was marginally less favorable in comparison to no fusion. Duplication of fusion gene showed worse prognosis. It was possible to determine the relative frequencies of PTEN deletion and/or TMPRSS2:ERG fusions in 82 of 125 prostate cancers. With biochemical recurrence as an endpoint, the genomic biomarkers identified three patient groups: (1) 'poor genomic grade' characterized by both PTEN deletion and TMPRSS2:ERG fusions (23/82, 28%); (2) 'intermediate genomic grade' with either PTEN deletion or TMPRSS2:ERG fusion (35/82, 43%) and (3) 'favorable genomic grade' in which neither rearrangement was present (24/82, 29%). Kaplan-Meier and multivariate analysis indicate that TMPRSS2:ERG fusion and PTEN loss together are a predictor of earlier biochemical recurrence of disease.

Because venous and lymphatic embolizations were related to greatest risk of lymph node metastasis, we propose their evaluation in staging and therapeutic planning of patients with infiltrative tumors of the penis.

BackgroundTOP2A encodes for topoisomerase IIα, a nuclear enzyme that controls DNA topological structure and cell cycle progression. This enzyme is a marker of cell proliferation in normal and neoplastic tissues; however, little information is available about its expression in prostate cancer (PCa).MethodsImmunohistochemistry (IHC) was automated using mouse monoclonal antibody against TOP2A (clone SWT3D1; DAKO, Carpenteria, CA, USA) at dilution 1:800 and Flex Plus detection system in autostainer 48Ultra (DAKO). FISH was performed using TOP2A (17q21)/ CEP17 probe kit (Kreateck Biotechnology, San Diego, CA, USA). Biochemical and pathological data from 193 patients with PCa were retrieved for the analysis, whose significance was considered when p < 0.05. Also, fractal analysis was performed in a subset of 20 randomly selected cases.ResultsTOP2A protein expression correlated with higher Gleason scores and higher levels of preoperative PSA (p = 0.018 and p = 0.011). Patients with higher levels of TOP2A presented shorter biochemical recurrence-free survival (BRFS) (p = 0.001). In multivariate analysis, we found that TOP2A remained an independent prognostic factor of BRFS, with a relative risk of 1.98 (p = 0.001; 95% CI, 1.338–2.93); thus, cases that expressed high levels of this enzyme had a shorter BRFS compared with TOP2A-negative or TOP2A-low cases. No alterations in TOP2A gene status nor correlation between FISH and IHC results were observed. Concerning fractal analysis, patients who expressed higher levels of TOP2A have angiolymphatic invasion and presented higher Gleason scores (p = 0.033 and p = 0.025, respectively). Also, patients with higher expression of TOP2A presented shorter BRFS (p = 0.001).ConclusionsThis is the first study to perform TOP2A protein and gene digital assessment and fractal analysis in association with BRFS in a large series of PCa. Also, we show that TOP2A gene copy number alterations are not observed in this type of tumor. So, higher protein expression of TOP2A is not related to gene amplification in PCa. Furthermore, TOP2A protein assessment has prognostic importance and, due to its relation with poor outcome, TOP2A IHC evaluation in the biopsy can represent an important tool for selecting the most suitable surgical and clinical approach for patients with PCa.

Cancer stem cells (CSCs) refer to a subset of tumor cells that self-renew and affect tumor heterogeneity. This model has attracted considerable interest in recent years due to its implications in the prognosis and clinical management of cancer because CSCs mediate the occurrence, growth, and recurrence of tumors. OCT4 is central to embryonic stem cell self-renewal and differentiation into specific lineages and encodes two chief isoforms that are generated by alternative splicing--OCT4A and OCT4B. Their function in prostate cancer (PCa) is unknown. The prognostic function of OCT4 isoforms in PCa samples was examined by immunohistochemistry (IHC) and sensitivity and specificity of the antibodies used were evaluated by molecular biology techniques. Biochemical and pathological data and specimens from 193 patients with PCa were evaluated retrospectively. IHC, western blot, immunofluorescence, and automated image analysis were also performed. IHC was performed on a tissue microarray, and western blot and immunofluorescence were performed using the PCa cell line DU-145. IHC expression of OCT4 isoforms correlated with biochemical and pathological parameters, particularly biochemical recurrence-free survival (BCRFS). Patients with higher levels of OCT4B had lower Gleason scores and decreased likelihood of experiencing biochemical recurrence (BR). OCT4A(+) OCT4B(-) patients had the shortest BCRFS, and positivity for OCT4B expression was an independent prognostic factor for BCRFS in the multivariate analysis. We conclude that the expression of OCT4B is a strong marker of good prognosis, and its presence is associated with a decreased likelihood of BR. Thus, OCT4B might represent a powerful clinical prognostic biomarker for PCa patients.

What ' s known on the subject? and What does the study add?The presence of invasion of renal vein and perinephric fat are predictors of poor outcome in patients with RCC. The latest version of the TNM system included tumours exhibiting such parameters in the T3a stage, thus grouping tumours with distinct pathologic features.Our study showed that patients with RCC presenting concomitant invasion of the renal vein invasion and perinephric fat invasion have signifi cantly worse survival rates than those showing any of the parameters separately. Therefore, we conclude that these tumours should not be grouped within T3a stage since they have signifi cantly different outcomes. OBJECTIVE• To evaluate the prognostic impact of tumor fat invasion (FI) and renal vein invasion (RVI) in patients with T3a renal cell carcinoma. PATIENTS AND METHODS• In total, 220 consecutive patients treated for renal cell carcinoma between 1992 and 2009 were analyzed. T3a stage cases were selected.• A single pathologist reviewed all cases. RESULTS• The present study cohort included 46 patients with mean follow-up of 28.6 months, of whom 17 (36.9%) died from disease. Patients were initially divided into three groups including 24 (52.1%) of FI only, 11 (23.9%) of RVI only and 11 (23.9%) of both FI and RVI.• In univariate analysis, no signifi cant differences in disease-specifi c survival (DSS) were noted between FI only and RVI only groups ( P = 0.91). DSS was signifi cantly worse in the FI + RVI group compared to the other groups ( P = 0.02).• When grouped into FI or RVI vs FI + RVI, DSS remained signifi cantly lower in the group containing the parameters concurrently ( P = 0.009). Progression-free survival also was signifi cantly lower in FI + RVI group ( P = 0.01).• Metastasis, positive lymph nodes and the presence of FI + RVI remained as isolated predictors of survival.• Patients with FI + RVI presented a 2.6-fold increase in risk of death from cancer and a 2.5-fold increase in risk of disease progression ( P = 0.04) compared to those with either of them alone. CONCLUSION• The isolated or concomitant presence of FI and RVI may be used as one of the criteria for staging in the next edition of the Tumour-Node-Metastasis classifi cation because they have signifi cantly different outcomes. KEYWORDSkidney , renal carcinoma , prognosis , oncology Study Type -Therapy (case series) Level of Evidence 4

DBWC is a safe and efficient alternative for simultaneous urinary and fecal diversion, with low morbidity and mortality rates, improvement of renal insufficiency, and low risk of postoperative urinary tract infection.

Penile carcinomas (PeCa) are relatively rare, but devastating neoplasms, more frequent among people of underprivileged socioeconomic status. There is mounting evidence that immune cells may trigger various mechanisms that enhance tumor growth and metastasis, but no data on the peritumoral inflammation is available for PeCa. The objectives of the present study are to evaluate the immunohistomorphology of tumoral inflammation in PeCa, and to correlate it with clinicopathological parameters, which could contribute to the prognostic evaluation. One hundred and twenty-two patients with the diagnosis of usual-type squamous cell penile carcinoma were included. Paraffin-embedded tissue was submitted to immunohistochemical evaluation of p16 protein, CD3, CD4, CD8, CD20, CD68, CD138, granzyme B, and Fox-P3. The Fisher's exact test was employed for comparison between histological variables and parameters, and the Kaplan-Meier method for the analysis of survival. Improved 5-year overall survival was significantly associated to age ≤60 years, stage I + II, tumor size T1 + T2, lymph node status N0, and absent perineural invasion. In a multivariate analysis age ≥60 years, presence of lymph node metastasis, urethral invasion, and high histologic grade retained a significantly more unfavorable outcome. Improved 5-year failure free survival was associated to stage of the disease I + II, lymph node status N0, absence of perineural, vascular, and urethral invasion, and Fox-P3 expression. In a multivariate analysis, presence of lymph node metastasis, perineural and vascular invasion, and of Fox-P3-positive lymphocytes together with low inflammatory infiltrate retained a significantly more unfavorable outcome. These results support the prognostic value of determining the levels of Fox-P3-positive lymphocytes by immunohistochemistry in PeCa, as this parameter adds value to the traditional clinicopathological features.