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The authors report the results of the grading of urothelial papillary carcinoma using histomorphometry and pattern recognition analysis. Features concerning nuclear area, the nuclear roundness factor and inclination angle were measured in 38 cases of urothelial papillary carcinomas. The relative frequency distribution showed overlapping among the grades with a reduction in the practical significance of histomorphometry. To overcome this problem, the pattern recognition analysis was applied. It was found that mean nuclear area, mean roundness factor and percentages of round and horizontal nuclei represent the optimal discriminating set of the subsequent steps in the malignant urothelial transformation.

Background/Aims The chromatin remodeler DAXX, a predominantly nuclear protein, regulates the status of chromatin organization. The aim of this exploratory immunohistochemical study was to evaluate DAXX protein expression in high grade invasive urothelial carcinoma (UC) of the bladder as a biological regulator of aggressiveness. Methods Quantitative analysis was made on DAXX immunostained nuclei in tissue sections from 5 cases of bladder normal urothelium (NU) and 5 cases of bladder pT1 UC. Carcinoma in situ (CIS) and high grade papillary carcinoma (HGPCa) were identified in 2 out of 5 UC cases. Results The nuclei in UC show an open configuration of the chromatin composed of granules varying in size and distribution and a mean nuclear area 1.7 times greater than that in NU (UC: mean and SD 24.4 ± 11.4 square microns; NU: 14.8 6.5 square microns. The differences are statistically significant). 70% of the NU nuclei are immunostained, whereas 90% of UC nuclei are positive. The mean gray level value in UC, related to the intensity of nuclear immunostaining, is lower than in NU by a factor of 0.94 (UC: mean and SD 100 ± 15; NU: 106 ± 15. The differences are statistically significant). In particular, the value in the nuclei adjacent to the stroma in UC is slightly lower than in the intermediate cell layers by factor of 0.98, whereas in NU it is slightly greater by a factor 1.02 and 1.04 compared to the intermediate and superficial cell layers. The values in CIS and HGPCa are similar to those in UC. Conclusions The quantitative immunohistochemical analysis shows an altered protein expression of chromatin remodeler DAXX in UC and in its preinvasive phases, when compared to NU. DAXX evaluation, if associated with markers related to global DNA methylation and histone acetylation, could be used in clinical practice as a marker of aggressiveness. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1398457297102379

Background: Cancer metabolism is emerging as a promising research area in genitourinary tumors. Both renal cell carcinoma (RCC) and prostate cancer (PCa) cells exhibit marked alterations of their metabolism. These changes include increased aerobic glycolysis (the Warburg effect), increased protein and DNA synthesis and de novo fatty acid (FA) synthesis. Objective: Understanding the molecular mechanisms underlying such alterations will represent a major step forward in cancer research. Indeed, reprogramming cancer cell energy metabolism represents a promising hallmark of cancer and may pave the way for novel personalized approaches. Method: PubMed databases were searched for articles published about cancer metabolism in genitourinary tumors. Results and Conclusion: This review is focused on the metabolic alterations that occur in RCC and PCa and describes the mechanisms underlying such metabolic changes.

Background There is a worldwide debate involving clinicians, uropathologists as well as patients and their families on whether Gleason score 6 adenocarcinoma should be labelled as cancer. Case description We report a case of man diagnosed with biopsy Gleason score 6 acinar adenocarcinoma and classified as low risk (based on a PSA of 5 ng/mL and stage cT2a) whose radical prostatectomy specimen initially showed organ confined Gleason score 3 + 3 = 6, WHO nuclear grade 3, acinar adenocarcinoma with lymphovascular invasion and secondary deposit in a periprostatic lymph node. When deeper sections were cut to the point that almost all the slice present in the paraffin block was sectioned, a small tumor area (

Renal cell carcinoma (RCC) is one of the most immunoresponsive human cancers. High-dose IL-2 and Interferon-α were once the principle therapies for metastatic RCC, however they had harsh-tolerance profiles and limited response rates. In the last decade, targeted therapies have supplanted cytokine therapy due to higher response rates and more favorable toxicity profiles. Emerging immunotherapies targeting the PD-1 receptor and PD-L1 ligand have shown promising results. Likewise, other novel targeted immunotherapies are currently under evaluation. The safety profiles and response rates of new generation immunotherapies are encouraging and justify the progression of clinical trials. However, longer follow-up data are needed to confirm these promising results. In addition, it is still unclear if an optimal sequence or combinations of new immunotherapies paired with current targeted therapies will emerge.

// Rossana Berardi 1 , Alessandro Brunelli 2 , Silvia Pagliaretta 1 , Vittorio Paolucci 1 , Alessandro Conti 4 , Gaia Goteri 5 , Majed Refai 3 , Cecilia Pompili 2 , Giulia Marcantognini 1 , Francesca Morgese 1 , Zelmira Ballatore 1 , Agnese Savini 1 , Mariagrazia De Lisa 1 , Miriam Caramanti 1 , Matteo Santoni 1 , Antonio Zizzi 5 , Francesco Piva 6 , Paola Mazzanti 1 , Azzurra Onofri 1 , Armando Sabbatini 3 , Marina Scarpelli 5 , Stefano Cascinu 1 1 Medical Oncology, Universita Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I – GM Lancisi – G Salesi, Italy 2 Department of Thoracic Surgery, St. James’s University Hospital, Leeds, West Yorkshire, United Kingdom 3 Thoracic Surgery, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I – GM Lancisi – G Salesi, Italy 4 Urology, Universita Politecnica delle Marche, Ancona, Italy 5 Section of Pathological Anatomy and Histopathology, Universita Politecnica delle Marche, Ancona, Italy 6 Department of Specialistic Clinical and Odontostomatological Sciences, Universita Politecnica delle Marche, Ancona, Italy Correspondence to: Rossana Berardi, e-mail: r.berardi@univpm.it Keywords: angiogenesis, prognosis, single nucleotide polymorphism, thymic epithelial tumor, tumor risk Received: April 04, 2015 Accepted: May 26, 2015 Published: June 08, 2015 ABSTRACT We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome. DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays. As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A ( p < 0.05). Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.

The aim of this essay is the self assessment of the level of knowledge of the 2004 WHO classification of bladder neoplasms through a series of MCQs, each associated a short commentary. This paper is directed to all who are involved with the application of this classification at the anticancer research, diagnostic, prognostic and therapeutic levels, in particular to uropathologists, urologists and oncologists.