Purpose Urocortin (Ucn) exerts its actions through activation of two corticotropin-releasing factor receptors (CRFRs), CRFR1 and CRFR2. Involvement of Ucn/ CRFR2 system in pathophysiological conditions such as the regulation of angiogenesis and inhibition of proliferation has been already reported. Suppression of neovascularization through reduction of vascular endothelial growth factor and inhibition of tumor cell cycling is modulated mainly through activation of CRFR2. To Wnd out a possible involvement of Ucn/CRFR2 in kidney tumor, we examined the expression of Ucn and CRFR2 in normal and tumoral kidney specimens. Methods We applied reverse transcriptase PCR (n = 14), immunoXuorescence (IF) on tissue microarrays (n = 25) and confocal microscopy to examine the mRNA expression and peptide/protein localization of Ucn and CRFR2 in normal kidney versus clear cell renal cell carcinoma, respectively.Results Ucn and CRFR2 mRNAs are expressed in normal and tumor specimens. In normal tissue, IF showed a cytoplasmic staining of Ucn mainly in proximal tubules, whereas a diVuse nuclear staining with diverse intensity was observed in tumoral tissues. CRFR2 was detected in proximal tubules and vasculature of normal specimens. Intriguingly, an almost complete loss of CRFR2 was observed in epithelial cells and microvessels within tumor tissues. Conclusions Here, and for the Wrst time, we show the expression of Ucn and CRFR2 in human kidney and renal cell carcinoma. We propose that the nuclear translocation of Ucn along with the loss of CRFR2 in epithelial cells and microvasculature of tumoral specimens may be involved in the pathobiology of renal cell carcinoma.
Three different treatment strategies for patients with stage I non-seminomatous testicular cancer are available that will all result in long-term survival in more than 98% of the patients: a "wait and see" strategy with follow-up and chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy, with or without application of systemic chemotherapy, in cases of retroperitoneal metastases (pathological stage II disease) or primary adjuvant chemotherapy following inguinal orchiectomy. Each treatment strategy is associated with specific side-effects. In several studies histological characteristics of the primary tumour, particularly the presence of vascular invasion and of embryonal carcinoma cells, have been demonstrated to be significant prognostic factors for the risk of occult retroperitoneal metastases in patients with stage I disease. In addition, new biological prognostic factors determined by flow cytometry, cytogenetic analysis or molecular-biological DNA or RNA analysis have been investigated, among which alterations of the p53 tumour-suppressor gene may represent a promising new prognostic factor. Although alterations of p53 gene expression seem to be associated with advanced tumour stage and may predict retroperitoneal metastatic disease, the independent role of these molecular genetic alterations needs to be prospectively studied. Currently a risk-adapted treatment strategy based on the histological criteria of vascular invasion and the presence of embryonal carcinoma can be used to stratify patients into a "high-" and "low-risk" group with respect to tumour progression. While primary-nerve-sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles of platinum, etoposide and bleomycin may be appropriate for patients with a high risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used for "low-risk" (less than 15% risk of progression) patients. Molecular investigations of prognostic factors may be able to improve further the stratification of patients into these different risk categories.
Positron emission tomography (PET) with the use of ((18)F)2-fluoro-D: -2-desoxyglucose (FDG) has been investigated to be a highly sensitive and specific imaging modality in the diagnostic of primary and recurrent tumors and in the control of therapies in numerous non-urologic cancers. The aim of this review is to validate the significance of PET as a diagnostic tool in malignant urological tumors of the small pelvis. A systematic review of the current literature concerning the role of PET for malignant prostate, testicular and bladder tumors was carried out. The data indicate no additional role for PET in comparison with conventional imaging in tumor detection and local staging for prostate, bladder or testicular cancer. Tumor recurrence in prostate cancer seems to be more effectively identified with acetate and choline than with FDG, but this effect is more pronounced with higher PSA values. The value of PET in the identification of metastatic disease in either tumor entity can not be finally outlined as the clinical data are partly missing, controversial or in the process of evaluation. FDG-PET can be regarded as accepted imaging modality in the restaging of seminomatous germ cell tumors after chemotherapy.
Tissue microarrays (TMAs) are used to simultaneously study the expression of proteins in hundreds of tissue samples, offering the important advantage to screen large tissue banks for biomarker expression and to simultaneously examine serial sections obtained from the same tumor specimen by a time- and cost-effective analytical approach. This review article presents an overview of the importance and the impact of this technique in cancer research with increasing number of investigations using TMAs in its eighth anniversary. Its application, limitations, and selected previous study results regarding urologic malignancies are presented and discussed.
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