Grade Of Renal Cell Carcinoma Research Articles

Renal Cell Carcinoma in Children: About Two Case Report

Introduction Renal cell carcinoma (RCC) is extremely rare in children. Several factors could influence prognosis, including stage, grade, histology, symptomatic presentation, and performance status. Among these, tumor stage is the most important predictor of disease prognosis for RCC. We report our experience with two cases of children with renal cell carcinoma in children. Cases Case 1: A 13-year-old girl presented macroscopic hematuria after a right lumbar trauma. The renal ultrasonography and CT urography showed a very limited rounding medio renal mass. Fine needle renal aspiration objectified RCC. Patient underwent transabdominal radical nephrectomy. Histopathology revealed RCC grade 2 of Furhrman T1b N0 M0. The postoperative course was uneventful. Case 2: A 9-year-old girl presented macroscopic hematuria. The renal ultrasonography showed a horseshoe left kidney with limited rounding mass. CT urography showed limited left renal mass of 31 × 25 mm. Fine needle renal aspiration objectified RCC. Patient underwent transabdominal radical nephrectomy with regional lymphadenectomy. Histopathology revealed RCC associated with translocation Xp11.2 grade 2 of Furhrman T1a N1M0. The postoperative course was uneventful. Conclusion RCC is rare in children but in children older than 5 years with renal masses it is very important to suspect diagnosis. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated.

Gleason and Fuhrman no longer make the grade.

Grading is an important prognostic parameter for prostate adenocarcinoma and renal cell carcinoma (RCC); however, the most frequently used classifications fail to account for advances in our understanding of the diagnostic features, classification and/or behaviour of these tumours. In 2005 and 2014, the International Society of Urological Pathology (ISUP) proposed changes to Gleason scoring with the adoption of the ISUP grading for prostate cancer in 2014 (grade 1, score 3 + 3; grade 2, score 3 + 4; grade 3, score 4 + 3; grade 4, score 8; grade 5, score 9-10). Internationally the Fuhrman grading system is widely employed despite criticisms related to its application, validity, and reproducibility. In 2012, the ISUP established a grading system for RCC (grade 1, the nucleolus is not seen or is inconspicuous and basophilic at ×400 magnification; grade 2, nucleoli are eosinophilic and clearly visible at ×400 magnification; grade 3, nucleoli are clearly visible at ×100 magnification; grade 4, tumours show extreme pleomorphism or rhabdoid and/or sarcomatoid morphology). This grading has been validated for clear cell RCC and papillary RCC. It was further recommended that chromophobe RCC not be graded. For other morphotypes of RCC, ISUP grading has not been validated as a prognostic parameter, but can be used for descriptive purposes.

83 Effectiveness of computed tomography for predicting the nuclear grade of renal cell carcinoma

83 Effectiveness of computed tomography for predicting the nuclear grade of renal cell carcinoma

Incidence of Clear Cell Papillary Renal Cell Carcinoma in Low-Grade Renal Cell Carcinoma Cases: A 12-Year Retrospective Clinicopathologic Study From a Single Cancer Center.

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognized subtype of renal cell carcinoma entity after 2004 World Health Organization classification of renal tumors. CCPRCC has unique histomorphological and immunohistochemical characteristics. The distinction of CCPRCC from renal cell carcinoma (RCC) with clear cell morphology is crucial because the former is considered to have a favorable clinical outcome. CCPRCC may be interpreted in the past as other renal cell carcinomas, particularly low-grade clear cell RCC. In this study, the frequency of CCPRCC in previously diagnosed low-grade RCC and its clinicopathologic features were examined. A total of 126 cases of stage T1a with low nuclear grade RCC were identified from 625 consecutive RCCs removed by radical/partial nephrectomy over 12-year period (2000-2011). Archival tissue sections were retrospectively reviewed along with patient medical charts. Eight cases (1.3% of all RCC, 6.3% of pT1a low grade RCC) with characteristic histologic features of CCPRCC were confirmed by immunohistochemical studies. Seven cases were previously diagnosed as clear cell RCC and one as multilocular cystic RCC. Radiographically, CCPRCC favored a mid-pole location in the kidneys. At a median follow-up period of 52 months (range 20-114.5 months), there were no cases of local or distant recurrence. In conclusion, CCPRCC is not uncommon among small low-grade RCC tumors. CCPRCC can be correctly recognized by its unique histomorphological features and confirmed by immunohistochemistry studies, which is important due to the excellent clinical outcome following resection.

Correlation of diffusion tensor imaging parameters and histopathology in the evaluation of renal clear cell carcinoma

Objective To investigate the correlation between the diffusion tensor imaging (DTI) parameters and histopathology in renal clear cell carcinoma patients. Methods Thirty renal clear cell carcinoma patients with lesions more than 1 cm in diameter were retrospectively analyzed.All patients had DTI and apparent diffusion coefficient (ADC),eigenvector 1(E1),fractional anisotropy(FA) value in normal kidney and lesion were measured respectively.The lesions were analyzed according to the Fuhrman nuclear grade for pathological findings.They were divided into two groups, namely high (Ⅲ–Ⅳ)and low (Ⅰ–Ⅱ) grade groups. In addition, the cell density,micro-vessel density (MVD) of turmor were also measured.The differences between two groups in cell density,micro-vessel density were analyzed by independent samples t test, the difference among normal kidney,high and low grade groups of clear cell renal cell carcinoma were compared using ANOVA.The correlationsamong ADC,E1,FA value and cell density, micro-vessel density were analyzed using Pearson analysis. Results Fifteen cases of renal clear cell carcinoma were of low grade (level Ⅰ,8 cases, level Ⅱ,7 cases), 15 cases were of high grade (level Ⅲ,9 cases, level Ⅳ,6 cases). The cell density of low and high grade tumors were (51.73±6.73)%, and (64.87±9.08)% respectively, the microvessel density were (49.33±7.76)/HP, and (61.27±8.45)/HP respectively. There were significant differences found(t= -4.50, -4.03, P<0.05). The ADC of normal renal tissues and low, high grade renal clear cell carcinoma were (2.08±0.10) ×10-3, (1.24±0.19) × 10-3, (1.08±0.19) × 10-3 mm2/s respectively, the E1 value were (2.19±0.15)×10-3, (1.44±0.16)×10-3,(1.21±0.21)×10-3mm2/s,respectively, and the FA were 0.32±0.05, 0.29±0.08, 0.22±0.06, respectively. There were significant differences in ADC,E1,FA values (F=148.347,127.366, 11.511,P<0.05). Cell density was negatively correlated to ADC,E1, FA values (r= -0.796, -0.865, -0.730; P<0.05). The correlation between ADC,E1, FA values and MVD were negatively correlated(r= -0.739, -0.826, -0.761;P<0.05). Conclusion DTI parameters are correlated with pathological classification of renal clear cell carcinoma. Key words: Renal neoplasms; Magnetic resonance imging; Pathology

Mucinous tubular and spindle cell renal cell carcinoma: a review of clinicopathologic aspects.

Mucinous tubular and spindle cell renal cell carcinoma is a rare, recently described variant of renal cell carcinoma characterized by an admixture of cuboidal cells in tubules and sheets of spindle cells, and variable amounts of mucinous stroma. It has been recognized as a distinct entity in the 2004 World Health Organization tumor classification. Since then, several dozen of these tumor have been reported with additional complementary morphologic characteristics, immunohistochemical profile, and molecular genetic features that have further clarified its clinicopathologic aspects. Although originally considered as a low grade renal cell carcinoma on the basis of its bland appearing nuclear features and indolent clinical course, mucinous tubular and spindle cell renal cell carcinoma has currently been proven to be a tumor that has a histological spectrum ranging from low to high grade that includes sarcomatoid differentiation. In this review, we present a detailed summary of the current knowledge regarding the clinicopathologic, immunohistochemical, molecular genetic, and prognostic characteristics, as well as differential diagnoses of mucinous tubular and spindle cell renal cell carcinoma.

Abstract 237: Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma

Abstract Introduction: Piwi-interacting RNAs (piRNAs) consists a newly discovered class of non-coding RNA. PiRNAs were first identified in the germ cells of various animal species. They bind to Piwi proteins which are a subfamily of Argonaut proteins. In humans were identified four Ago genes and four Piwi genes. Human Piwi genes include PIWIL1, PIWIL2, PIWIL3 and PIWIL4. Recent studies suggest that deregulated expression of Piwi proteins is common to many types of tumors and also correlate with clinicopathologic features and worse prognosis in patients with breast, cervical, ovarian, colorectal and other cancers. PiRNAs are short single-stranded RNAs with 26-31 nucleotides in length. They are involved in silencing of transposable elements and it is assumed that also participate in sequence-specific chromatin modifications. The differential expression of piRNAs was found in gastric and breast cancer. In our pilot study we analyzed expression of Piwi genes and piR-651, which was previously found to be deregulated in various types of tumors. Patients and Methods: In our study, we have used the tumor tissue and the paired renal parenchyma tissue of 56 patients with renal cell carcinoma (RCC). From the tissue was isolated total RNA and by RT-qPCR were examined the expression of Piwi genes and piR-651. For the analysis of circulating piR-651, blood serum samples of 75 patients with RCC and 75 age, gender-matched healthy donors were used. We have compared expression levels of the studied genes in tumor and non-tumor tissues, serum samples, and also correlated them with clinicopathologic features of RCC patients (stage, grade, RFS, OS). Results: We found a significant down-regulation of PIWIL1 (p&amp;lt;0,0001) and piR-651 (p&amp;lt;0,0001) expression levels in tumor tissue when compared to paired renal parenchyma samples. The expression levels of PIWIL2, PIWIL3 and PIWIL4 were not significantly deregulated in tumor tissue. Interestingly, levels of PIWIL2 and PIWIL4 correlated significantly with the stage (p = 0,002 and p = 0,003, resp.) and grade (p = 0.007 and p&amp;lt;0.0001, resp.) of RCC. We found also a correlation between higher levels of PIWIL1 and overall survival (p&amp;lt;0.05). We have observed significantly decreased expression levels of piR-651 in blood serum samples of RCC patients when compared to healthy donors and accordingly to ROC analysis we were able to distinguish blood serum of RCC patients and control subjects with the sensitivity of 77.33% and a specificity of 72.37%. Expression levels of serum piR-651 were not in correlation with the stage and grade of RCC. Conclusion: Accordingly to our pilot data expression of Piwi genes is altered in tumor tissue and is correlated to selected clinicopathologic features of RCC. We also suggest the potential of piR-651 in blood serum as novel non-invasive diagnostic biomarker in RCC. Acknowledgments: IGA MZCR No: NT/13860-4/2012, NT/13549-4/2012, NT/13547-4/2012, NT/13514-4/2012 Citation Format: Robert Iliev, Petra Vychytilova-Faltejskova, Jaroslav Juracek, Hana Mlcochova, Michal Stanik, Jan Dolezel, Michal Fedorko, Dalibor Pacik, Marek Svoboda, Ondrej Slaby. Piwi genes and tissue/serum piR-651 are related to clinicopathologic features of renal cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 237. doi:10.1158/1538-7445.AM2015-237

High serum miR-183 level is associated with poor responsiveness of renal cancer to natural killer cells.

Renal cell carcinoma (RCC) is among the most common subtype of kidney cancers, and the current therapeutic strategies are not efficient. Natural killer (NK) cells are biological agents that can induce apoptosis in a wide range of cancer cells. However, most of RCC patients exhibit resistance against the action of NK cells due to unknown mechanisms. This study is aimed to identify a biomarker that can predict the response of RCC cells to NK cell treatment. We collected 82 RCC patients and 19 healthy volunteers to detect the expression of miR-183 in blood by qPCR assays. The results revealed that serum miR-183 is significantly higher in RCC patients than in healthy controls, and its level is positively associated with the grading of RCC. Furthermore, (51)Cr release assays indicated that the primary RCC cells with low serum miR-183 expression are more sensitive to the cytotoxicity of NK cells. Collectively, we demonstrated that serum miR-183 can be used to predict the response of RCC cells to the cytotoxicity induced by NK cells.

Overexpression of YB1 and EZH2 are associated with cancer metastasis and poor prognosis in renal cell carcinomas.

Renal cell carcinoma (RCC) is the most common type of kidney cancers in adults, and metastasis represents the major cause of mortality of RCC patients. The Y-box binding protein 1 (YB1) is a multifunctional oncoprotein in various malignancies. Enhancer of zeste homolog 2 (EZH2), a polycomb histone methyltransferase, is a key epigenetic modifier implicated in various cancer metastasis. However, the expression patterns and clinical correlations of both YB1 and EZH2 in RCC remain largely unclear. In this study, the expression of YB1 and EZH2 were examined using immunohistochemistry staining in a study cohort including 165 RCC and 80 tumor adjacent normal tissues. RCC tissues showed a significant higher nuclear expression of YB1 (p < 0.001) and EZH2 (p < 0.001) as compared with the normal counterparts. In addition, YB1 and EZH2 nuclear overexpression were found to be positively associated with RCC stage (p < 0.001 and p = 0.005), Fuhrman tumor grade (p = 0.022 and p = 0.044), and metastasis (p < 0.001 and p = 0.009). Overall survival analysis indicated patients with YB1 (p = 0.004, HR 5.656 (2.006-10.944)) and/or EZH2 (p = 0.006, HR 4.551 (2.124-9.438)) nuclear overexpression correlated with poor survival. More interestingly, YB1 and EZH2 nuclear expression was correlated (p = 0.005). Further studies demonstrated that EZH2 expression was significantly downregulated in YB1 knockdown RCC cell lines. Functionally, YB1 knockdown inhibited RCC invasion in vitro. In conclusion, YB1 and EZH2 expression was correlated and associated with RCC incidence, tumor stage, grade, metastasis, and survival.

The value of blood oxygenation level-dependent (BOLD) MR imaging in differentiation of renal solid mass and grading of renal cell carcinoma (RCC): analysis based on the largest cross-sectional area versus the entire whole tumour.

ObjectivesTo study the value of assessing renal masses using different methods in parameter approaches and to determine whether BOLD MRI is helpful in differentiating RCC from benign renal masses, differentiating clear-cell RCC from renal masses other than clear-cell RCC and determining the tumour grade.MethodsNinety-five patients with 139 renal masses (93 malignant and 46 benign) who underwent abdominal BOLD MRI were enrolled. R2* values were derived from the largest cross-section (R2*largest) and from the whole tumour (R2*whole). Intra-observer and inter-observer agreements were analysed based on two measurements by the same observer and the first measurement from each observer, respectively, and these agreements are reported with intra-class correlation coefficients and 95% confidence intervals. The diagnostic value of the R2* value in the evaluation was assessed with receiver-operating characteristic analysis.ResultsThe intra-observer agreement was very good for R2*largest and R2*whole (all > 0.8). The inter-observer agreement of R2*whole (0.75, 95% confidence interval: 0.69~0.79) was good and was significantly improved compared with the R2*largest (0.61, 95% confidence interval: 0.52~0.68), as there was no overlap in the 95% confidence interval of the intra-class correlation coefficients. The diagnostic value in differentiating renal cell carcinoma from benign lesions with R2*whole (AUC=0.79/0.78[observer1/observer2]) and R2*largest (AUC=0.75[observer1]) was good and significantly higher (p=0.01 for R2*largest[observer2] vs R2*whole[observer2], p<0.01 for R2*whole[observer1] vs R2*largest[observer2]) than R2*largest for observer 2 (AUC=0.64). For the grading of clear-cell RCC, both R2*whole and R2*largest were good (all > 0.7) and were not significantly different (p=0.89/0.93 for R2*largest vs R2*whole[observer1/observer2], 0.96 for R2*whole[observer1] vs R2*largest[observer2] and 0.96 for R2*whole [observer2] vs R2*largest[observer1]).ConclusionsBOLD MRI could provide a feasible parameter for differentiating renal cell carcinoma from benign renal masses and for predicting clear-cell renal cell carcinoma grading. Compared with the largest cross-section, assessing the whole tumour provides better inter-observer agreement in parameter measurement for differentiating renal cell carcinoma from benign renal masses.

MP39-10 EFFECT OF OBESITY AND ADIPONECTIN SIGNALING IN PATIENTS WITH RENAL CELL CARCINOMA TREATED WITH SURGERY

You have accessJournal of UrologyKidney Cancer: Basic Research I1 Apr 2015MP39-10 EFFECT OF OBESITY AND ADIPONECTIN SIGNALING IN PATIENTS WITH RENAL CELL CARCINOMA TREATED WITH SURGERY Ryuichi Itoh, Shintaro Narita, Mingguo Huang, Hiroshi Tsuruta, Susumu Akihama, Mitsuru Saito, Takamitsu Inoue, Norihiko Tsuchiya, Shigeru Satoh, and Tomonori Habuchi Ryuichi ItohRyuichi Itoh More articles by this author , Shintaro NaritaShintaro Narita More articles by this author , Mingguo HuangMingguo Huang More articles by this author , Hiroshi TsurutaHiroshi Tsuruta More articles by this author , Susumu AkihamaSusumu Akihama More articles by this author , Mitsuru SaitoMitsuru Saito More articles by this author , Takamitsu InoueTakamitsu Inoue More articles by this author , Norihiko TsuchiyaNorihiko Tsuchiya More articles by this author , Shigeru SatohShigeru Satoh More articles by this author , and Tomonori HabuchiTomonori Habuchi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.760AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Obesity increases the risk for renal cell carcinoma (RCC), whereas obese patients appear to experience longer survival than non-obese patients. Inactivation of adiponectin signaling, which is a key regulator of obesity-related diseases, plays a role in the progression of RCC. Here we investigated the effect of obesity and adiponectin signaling in RCC patients treated with surgery. METHODS A total of 129 RCC patients treated with surgery were included in the analyses. Preoperative BMI, percentage of visceral adipose tissue (VAT) measured on CT scan, total adiponectin levels in the serum and perinephric adipose tissue condition medium by a specific ELISA, and intratumoral mRNA levels of AdipoR1 and AdipoR2 were statistically analyzed to assess the effect on pathological outcomes and survival. RESULTS Overweight and obese patients had a significantly lower grade cancer compared with normal weight patients in all patients and patients without metastasis (p = 0.003, p = 0.027, respectively). Disease-specific survival in overweight and obese patients was significantly longer compared with that in normal weight patients in all patients (p = 0.035), but not in patients without metastasis (p = 0.203). The percentage of VAT and serum adiponectin levels were not significantly associated with clinical outcomes of RCC patients. The mean adiponectin level of perinephric adipose tissue condition medium tended to be lower in patients with high grade RCC compared with healthy controls (p = 0.054). Although the mRNA expressions of AdipoR1 and AdipoR2 in tumors were not correlated with BMI and the VAT percentage, they were significantly lower in tumor tissues compared with normal renal tissues (p < 0.001, and p < 0.001, respectively). AdipoR1 expression in patients with high grade tumor was significantly lower compared with that in patients with low grade tumor (p = 0.030) and patients with sarcomatoid RCC had a significantly lower AdipoR1 expression compared with those with other histological subtypes (p = 0.001). CONCLUSIONS A high BMI may be associated with a better pathological outcome and survival in RCC patients treated with surgery. Impaired adiponectin secretion from enlarged adipose tissues and the inactivation of the intratumoral adiponectin receptor may be involved in RCC progression. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e457-e458 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ryuichi Itoh More articles by this author Shintaro Narita More articles by this author Mingguo Huang More articles by this author Hiroshi Tsuruta More articles by this author Susumu Akihama More articles by this author Mitsuru Saito More articles by this author Takamitsu Inoue More articles by this author Norihiko Tsuchiya More articles by this author Shigeru Satoh More articles by this author Tomonori Habuchi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Is thrombocytosis a useful prognostic marker in renal cell carcinoma? Results of a single-center retrospective analysis.

Introduction:Our aim was to determine the correlation of platelet count with stage and grade of renal cell carcinoma (RCC) and to determine whether progression of disease was more likely in those with thrombocytosis.Materials and Methods:A retrospective review of patients with RCC from January 2004 to December 2011 was undertaken. Patients with no preoperative platelet count and those with multiple tumors were excluded. Disease progression was defined as appearance of local recurrence or distant metastasis on follow-up. Thrombocytosis was defined as a platelet count of >400,000/cumm. Standard tests of significance and multivariate analysis using logistic regression were performed.Results:A total of 322 cases were identified. The median follow-up was 7 months (range, 2-84 months). The platelet count correlated significantly with higher Fuhrmann grade, as well as increasing TNM stage at diagnosis. Patients with a platelet count of >400,000/cumm (n = 35) had a significantly higher mean tumor size and worse grade at diagnosis than those with a normal platelet count (n = 287). Patients with thrombocytosis also had a significantly worse stage at presentation. Progression of disease was seen more often in patients with thrombocytosis (28.6% vs 11.9%, P = 0.07). The median time to progression was significantly faster in patients with thrombocytosis (9 vs 18 months, P = 0.018). However, on multivariate analysis TNM stage was the only significant predictor of time to progression.Conclusion:Rising platelet count correlated significantly with advancing stage and grade of disease. Patients with thrombocytosis were significantly more likely to have advanced tumors at presentation, poorer histological features, and rapid disease progression.

Methylation‑associated inactivation of LATS1 and its effect on demethylation or overexpression on YAP and cell biological function in human renal cell carcinoma.

Large tumor suppressor 1 (LATS1) gene is one of the key factors in Hippo signaling pathway. Inactivation of LATS1 by promoter methylation was found in colorectal cancer (CRC), head and neck squamous cell carcinoma (HNSCC), astrocytoma, breast cancer and it was proved to be a tumor suppressor. However, its role is unclear in renal cell carcinoma (RCC). In this study, the expression of LATS1 was determined by reverse transcription polymerase chain reaction (RT‑PCR) and immunohistochemistry in 30 pairs of RCC tissues and matched normal kidney tissues and RCC cells. We found that the expression of LATS1 was markedly reduced in RCC tissues and cells, in the RCC tissue in 46.7% (14/30), while in the normal kidney tissues in 76.7% (23/30), and was associated with pathological grade and clinical stage of RCC. We detected methylation status of LATS1 by bisulfite sequence-PCR (BSP) in renal cancer cell line 786-O which lowers expression of LATS1, and we found it hypermethy-lated (in 97.5%). In addition, pharmacological demethylation using 5-Aza-2'-deoxycytidine (5-Aza) restored the expression of LATS1 mRNA and protein in 786-O cells, both LATS1 demethylation and overexpression of LATS1 downregulated the expression of Yes-associated protein (YAP), inhibited cell proliferation, induced cell apoptosis and cell cycle G1 arrest in 786-O cells. Thus, this report for the first time demonstrates the inactivation of LATS1 by promoter methy-lation and it is a tumor suppressor in kidney cancer. LATS1 may serve as a biomarker for possible early diagnosis and as a potential therapeutic target for human RCC.

Rhabdoid Differentiation Is Associated With Aggressive Behavior in Renal Cell Carcinoma

Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP.

Multiparametric magnetic resonance imaging for the differentiation of low and high grade clear cell renal carcinoma.

To retrospectively evaluate the ability of magnetic resonance (MR) imaging to differentiate low from high Fuhrman grade renal cell carcinoma (RCC). MR images from 80 consecutive pathologically proven RCC (57 clear cell, 16 papillary and 7 chromophobe) were evaluated. Double-echo chemical shift, dynamic contrast-enhanced T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps were reviewed independently. Signal intensity index (SII), tumour-to-spleen SI ratio (TSR), ADC ratio, wash-in (WiI) and wash-out indices (WoI) between different phases were calculated and compared to pathological grade and size. The Fuhrman scoring system was used. Low grade (score ≤ 2) and high grade (score ≥ 3) tumours were compared using univariate and multivariate analyses. No associations between grade and imaging factors were found for papillary and chromophobe RCCs. For clear cell RCCs, there was a significant association between the grade and parenchymal WiI (WiI2) (P = 0.02) or ADCr (P = 0.03). A significant association between tumour grade and size (P = 0.01), WiI2 (P = 0.02) and ADCr (P = 0.05) remained in multivariate analysis. Multiparametric MRI can be used to accurately differentiate low Fuhrman grade clear cell RCC from high grade. High Fuhrman grade (≥ 3) RCCs were larger, had lower parenchymal wash-in indices and lower ADC ratios than low grade. • Fuhrman grade of clear cell RCC can be differentiated with multiparametric MR imaging. • Fuhrman grade significantly differed for size, parenchymal wash-in index and ADC ratio. • No significant associations were found for papillary and chromophobe renal cell carcinoma.

Interferon regulatory factor 8 functions as a tumor suppressor in renal cell carcinoma and its promoter methylation is associated with patient poor prognosis

Interferon regulatory factor 8 (IRF8), as a central element of IFN-γ-signaling, plays a critical role in tumor suppression. However, its expression and underlying molecular mechanism remain elusive in renal cell carcinoma (RCC). Here, we examined IRF8 expression and methylation in RCC cell lines and primary tumors, and further assessed its tumor suppressive functions. We found that IRF8 was widely expressed in human normal tissues including kidney, but frequently downregulated by promoter methylation in RCC cell lines. IRF8 methylation was detected in 25% of primary tumors, but not in adjacent non-malignant renal tissues, and associated with higher tumor nuclear grade of RCC. Ectopic expression of IRF8 inhibited colony formation and migration abilities of RCC cells, through inducing cell cycle G2/M arrest and apoptosis. IFN-γ could induce IRF8 expression in RCC cells, together with increased cleaved-PARP. We further found that IRF8 inhibited expression of oncogenes YAP1 and Survivin, as well as upregulated expression of tumor suppressor genes CASP1, p21 and PTEN. Collectively, our data demonstrate that IRF8 as a functional tumor suppressor is frequently methylated in RCC, and IRF8-mediated interferon signaling is involved in RCC pathogenesis.

Organ transplantation from donors (cadaveric or living) with a history of malignancy: review of the literature.

The evolution of organ transplantation has resulted in extended lifespan as well as better life quality of patients with end-stage diseases, which in turn causes an increased demand for organs. The persistent organ shortage requires a careful reconsideration of potential donors (living or cadaveric) that have current or historical malignancies. Donors with low-grade skin tumors, carcinomas in situ of the uterine cervix, and primary central nervous system (CNS) tumors can be considered as potential donors for recipients dying on wait list longing for organ transplantation. Recently, transplant centers have turned to other types of malignancies including low grade renal cell carcinoma, prostate, ureteral, endometrial and breast cancer, and favorable outcomes have been shown in such innovations. When considering donors with a history of malignancy, general biologic behavior of the tumor type, histology and stage at the time of diagnosis, and the length of disease-free interval should be considered (Transplantation 2002;74(12):1657-1663). With the review of literatures, we illustrate the organ utilization from donors with malignancies all around the world since earlier times and give some suggestions for decision making under the circumstance of whether to choose those marginal donors or not on the basis of reviewed literatures.

Expression and Proliferation-Promoting Role of Lymphoid Enhancer-Binding Factor 1 in Human Clear Cell Renal Carcinoma

Lymphoid enhancer-binding factor 1 (LEF1) has been regarded as an important gene for carcinogenesis in many malignancies, however, the role of LEF1 in the progression of human renal cell carcinoma (RCC) has not been well studied. In this study, we investigated the expression of LEF1 in human RCC and the effect on proliferative ability of RCC cells. RCC samples from 138 patients who underwent radical nephrectomy were used in this study, the expression of LEF1 protein was determined by immunohistochemistry and Western blot, mRNA expression was analyzed by RT-PCR and real-time PCR. To investigate the effect of LEF1 on the proliferation of RCC cells, a LEF1 vector was transfected into RCC cells and LEF1 expression was also decreased by using siRNA. Proliferative ability of RCC cells was examined by WST-1 assay and a xenograft study with BALB/C nude mice. Our results indicated that LEF1 expression was significantly increased in stage III, IV and grade 3 RCC than in normal kidney, however, decreased LEF1 expression was found in low-stage and grade RCC compared to that in normal kidney, the expression of LEF1 was correlated to tumor stages, histologic grade, and tumor sizes in RCC. The effect of LEF1 on the proliferation in RCC was also analyzed, our results suggested that RCC cells expressing high levels of LEF1 had significantly increased proliferative ability compared to control cell lines, in contrast, RCC cells with a low LEF1 expression had lower proliferative ability. Moreover, LEF1 promoted proliferation of RCC cells depending on suppressing G2/M cell-cycle arrest. Our study demonstrated that the expression of LEF1 is associated with the progression of RCC and that LEF1 maybe involved in the development of RCC, these suggested LEF1 play a key role and might serve as a therapeutic target in treating advanced RCC.

Diabetes mellitus as a risk factor for high grade renal cell carcinoma.

Diabetes is a chronic disease characterized by impaired fasting blood glucose that leads to disturbances in various organs. In this study, we evaluated relationships between tumor size and grade in a population of diabetic and non-diabetic patients with renal cell carcinoma. Between 2007-2013, in our clinic radical nephrectomy performed to 310 patients for renal tumors and pathology reported renal cell carcinoma cases were enrolled in the study. Patients with and without a history of diabetes regarding fasting glucose and HgA1c levels were evaluated during surgery for tumor size and Fuhrman grade. Diabetes was found in 95 patients. The mean age of the patients with and without diabetes mellitus was 64.3 (40-79) and 58.4 (31-87) years, respectively. In the diabetes group 51% of patients had a tumor size over 7 cm and 54% a tumor grade over Fuhrman 3. The respective figures in the non-diabetes group were 35% and 30% (p<0.05 in both cases). Renal cancer appears more aggressive in patients with diabetes. In this study lifestyle and risk factors with diabetes regulation were observed to be important for renal cancer patients. Multicenter studies are needed in larger series for more accurate results.

Expression and clinical significance of human antigen R and hypoxia inducible factor 1 alpha in renal cell carcinoma

Objective To investigate the clinical significance and correlation of human antigen R (HuR) and hypoxia inducible factor 1 alpha (HIF-1α) expressions in renal cell carcinoma (RCC).Methods Immuno-histochemistry PV9000 method was used to detect the expression of HuR and HIF-1α in 76 cases of RCC tissues,20 cases of para-carcinoma tissues and 15 cases of normal renal tissues.The correlation between the two proteins and clinical pathological parameters of RCC patients were analyzed.KaplanMeier estimates were used for survival analysis,and correlation analyses were conducted by using Spearman rank correlation method and chi-square test.Results The cytoplasm positive expression rate (38.2％) of HuR in RCC was higher than that in para-carcinoma tissues (10.0％) and normal renal tissues (13.3％,P＜0.05).The nucleus positive expression rate (48.7％) of HIF-1α in RCC was significantly higher than that in para-carcinoma tissues (5.0％) and normal renal tissues (0,P＜0.05).The expression level of HuR in cytoplasm was significantly correlated with the clinical stage,histological subtype and lymph node metastasis status (P＜0.05) in RCC.There was significant correlation between the expression level of nucleus HIF-1α and clinical stage,pathological grade and lymph node metastasis status in RCC (P＜0.05).There was positive correlation between cytoplasm HuR and nucleus HIF-1α expression level (P＜0.05) in RCC.Sixty-six RCC patients were followed up for 6 to 67 months,patients with negative cytoplasm HuR or negative nucleus HIF1α expression had better overall survival rate and longer mean survival time than those with positive expression (P＜0.05).Conclusions The expression levels of cytoplasm HuR and nucleus HIF-1α are associated with the clinical pathological parameter of RCC patients.HuR and HIF-1α may play an important role in the prognosis assessment of RCC patients. Key words: Carcinoma, renal cell; Human antigen R; Hypoxia inducible factor 1 alpha; Diagnosis ; Prognosis