Background: Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. Methods: Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed. Results: In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05). Conclusions: Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer.

Background: Histone deacetylases (HDACs) are known to be associated with an overexpression in different types of cancer such as colon and prostate cancer. In this study we aimed to evaluate the protein expression of class I HDACs in urothelial carcinoma of the bladder. Methods: A tissue microarray containing 348 tissuesamples from 174 patients with a primary urothelial carcinoma of the bladder was immunohistochemically stained for HDAC 1, 2 and 3. Intensity of staining was evaluated and the association with clinico-pathological features and prognosis was assessed. Results: High HDAC expression levels were found in 40 to 60% of all investigated urothelial carcinomas (HDAC-1: 40%, HDAC-2: 42%, HDAC-3: 59%). HDAC-1 and HDAC-2 were significantly associated with higher tumour grades. Although all three markers could not predict progression in univariate analyses, high HDAC-1 expression was associated with a trend toward poorer prognosis. Patients with high-grade tumours and high expression levels of HDAC-1 were more likely to progress compared to all other patients (p < 0.05). Conclusions: High-grade noninvasive papillary bladder tumours are associated with high expression levels of HDAC-1 and HDAC-2. High grade tumours in combination with high expression of HDAC-1 showed a worse prognosis than the other tumours. The high expression levels of HDACs observed particularly in high grade urothelial bladder cancer clearly warrant subsequent studies on the potential use of HDAC inhibitors as a novel therapeutic approach.

Epigenetic changes, including CpG island hypermethylation, occur frequently in bladder cancer (BC) and may be exploited for BC detection and distinction between high-grade (HG) and low-grade (LG) disease. Genome-wide methylation analysis was performed using Agilent Human CpG Island Microarrays to determine epigenetic differences between LG and HG cases. Pathway enrichment analysis and functional annotation determined that the most frequently methylated pathways in HG BC were enriched for anterior/posterior pattern specification, embryonic skeletal system development, neuron fate commitment, DNA binding, and transcription factor activity. We identified 990 probes comprising a 32-gene panel that completely distinguished LG from HG based on methylation. Selected genes from this panel, EOMES, GP5, PAX6, TCF4, and ZSCAN12, were selected for quantitative polymerase chain reaction-based validation by MethyLight in an independent series (n=84) of normal bladder samples and LG and HG cases. GP5 and ZSCAN12, two novel methylated genes in BC, were significantly hypermethylated in HG versus LG BC (P≤.03). We validated our data in a second independent cohort of LG and HG BC cases (n=42) from The Cancer Genome Atlas (TCGA). Probes representing our 32-gene panel were significantly differentially methylated in LG versus HG tumors (P≤.04). These results indicate the ability to distinguish normal tissue from cancer, as well as LG from HG, based on methylation and reveal important pathways dysregulated in HG BC. Our findings were corroborated using publicly available data sets from TCGA. Ultimately, the creation of a methylation panel, including GP5 and ZSCAN12, able to distinguish between disease phenotypes will improve disease management and patient outcomes.

Background: The oncofetal protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell-migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. To our knowledge, IMP3 expression has not been investigated in prostate carcinomas so far. Methods: Immunohistochemical stainings for IMP3 were performed on tissue microarray (TMA) organized samples from 507 patients: 31 normal prostate tissues, 425 primary carcinomas and 51 prostate cancer metastases or castration-resistant prostate cancers (CRPC). IMP3 immunoreactivity was semiquantitatively scored and correlated with clinical-pathologic parameters including survival. Results: IMP3 is significantly stronger expressed in prostate carcinomas compared to normal prostate tissues (p < 0.0001), but did not show significant correlation with the pT-stage, the proliferation index (MIB1), preoperative serum PSA level and the margin status. Only a weak and slightly significant correlation was found with the Gleason score and IMP3 expression failed to show prognostic significance in clinico-pathological correlation-analyses. Conclusions: Although IMP3 is overexpressed in a significant proportion of prostate cancer cases, which might be of importance for novel therapeutic approaches, it does not appear to possess any immediate diagnostic or prognostic value, limiting its potential as a tissue biomarker for prostate cancer. These results might be corroborated by the fact, that two independent tumor cohorts were separately reviewed.

Absorption of irrigation fluid was not detected during GreenLight™ laser vaporization of the prostate using the first generation 80 W laser. However, data are lacking on intraoperative irrigation fluid absorption using the second generation 120 W high power laser. We assessed whether fluid absorption occurs during high power laser vaporization of the prostate. We performed this prospective investigation at a tertiary referral center in patients undergoing 120 W laser vaporization for prostatic bladder outlet obstruction. Normal saline containing 1% ethanol was used for intraoperative irrigation. The expired breath ethanol concentration was measured periodically during the operation using an alcometer. The volume of saline absorption was calculated from these concentrations. Intraoperative changes in hematological and biochemical blood parameters were also recorded. Of 50 investigated patients 22 (44%) had a positive breath ethanol test. Median absorption volume in the absorber group was 725 ml (range 138 to 3,452). Ten patients absorbed more than 1,000 ml. Absorbers had a smaller prostate, more capsular perforation, higher bleeding intensity and more laser energy applied during the operation. Three patients (13%) had symptoms potentially related to fluid absorption. Hemoglobin, hematocrit and serum chloride were the only blood parameters that changed significantly in the absorber group. The changes were significantly different than those in nonabsorbers. Fluid absorption occurs frequently during high power laser vaporization of the prostate. This should be considered in patients who present with cardiopulmonary or neurological symptoms during or after the procedure.

Background: Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. Case presentation: A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed. Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. Conclusions: To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens.