Histological Subtypes Of Renal Cell Carcinoma Research Articles

Identification of a new aggressive axis driven by ciliogenesis and absence of VDAC1-ΔC in clear cell Renal Cell Carcinoma patients.

Rationale: Renal cell carcinoma (RCC) accounts for about 2% of all adult cancers, and clear cell RCC (ccRCC) is the most common RCC histologic subtype. A hallmark of ccRCC is the loss of the primary cilium, a cellular antenna that senses a wide variety of signals. Loss of this key organelle in ccRCC is associated with the loss of the von Hippel-Lindau protein (VHL). However, not all mechanisms of ciliopathy have been clearly elucidated.Methods: By using RCC4 renal cancer cells and patient samples, we examined the regulation of ciliogenesis via the presence or absence of the hypoxic form of the voltage-dependent anion channel (VDAC1-ΔC) and its impact on tumor aggressiveness. Three independent cohorts were analyzed. Cohort A was from PREDIR and included 12 patients with hereditary pVHL mutations and 22 sporadic patients presenting tumors with wild-type pVHL or mutated pVHL; Cohort B included tissue samples from 43 patients with non-metastatic ccRCC who had undergone surgery; and Cohort C was composed of 375 non-metastatic ccRCC tumor samples from The Cancer Genome Atlas (TCGA) and was used for validation. The presence of VDAC1-ΔC and legumain was determined by immunoblot. Transcriptional regulation of IFT20/GLI1 expression was evaluated by qPCR. Ciliogenesis was detected using both mouse anti-acetylated α-tubulin and rabbit polyclonal ARL13B antibodies for immunofluorescence.Results: Our study defines, for the first time, a group of ccRCC patients in which the hypoxia-cleaved form of VDAC1 (VDAC1-ΔC) induces resorption of the primary cilium in a Hypoxia-Inducible Factor-1 (HIF-1)-dependent manner. An additional novel group, in which the primary cilium is re-expressed or maintained, lacked VDAC1-ΔC yet maintained glycolysis, a signature of epithelial-mesenchymal transition (EMT) and more aggressive tumor progression, but was independent to VHL. Moreover, these patients were less sensitive to sunitinib, the first-line treatment for ccRCC, but were potentially suitable for immunotherapy, as indicated by the immunophenoscore and the presence of PDL1 expression.Conclusion: This study provides a new way to classify ccRCC patients and proposes potential therapeutic targets linked to metabolism and immunotherapy.

Biomarkers in renal cell carcinoma

We have entered a new era for patients with mRCC with multiple treatment options including VEGF(Vascular Endothelial Growth Factor)-, MET(Mesenchymal-eptihelial Transition)-, AXL(AXL-Rezeptortyrosinkinase)-, mTOR(mechanistic Target of Rapamycin)-targeted TKIs (tyrosinekinaseinhibitors) as well as PD-1(programmed cell death protein 1)-, PD-L1(Programmed cell death 1 ligand)- and CTLA4(cytotoxic T-lymphocyte-associated Protein 4)-targeted IOs and their combinations, respectively. However, the possibility to select patients based on predictive biomarkers for the different treatment options is still lacking. The TCGA (Cancer Genome Atlas) consortium conducted comprehensive analyses of genomic and metabolic features of RCC (renal cell carcinoma) and these findings demonstrated significant differences between the major histological subtypes of RCC like differences in immune signatures and their course of disease. The increasing knowledge on the genomic landscape of RCC supports stratification of patients for targeted therapies. Biomarker development for future therapeutic approaches will require integration of multiple biologic components like PD-L1 expression, tumor-infiltrating lymphocytes and mutations in addition to the prognostic risk scores. However, no single molecular marker has been shown to improve the accuracy of MSKCC (Memorial Sloan Kettering Cancer Center) or IMDC (International Metastatic RCC Database Consortium) prognostic risk scores. Large-scale biomarker-driven prospective trials with consensus methodologies on biomarker assessment and scoring are needed to obtain clinically validated new prognostic and predictive biomarkers as described above. The integration of routinely available parameters and new biomarkers could hold the key for personalized treatment strategies of patients with RCC.

Cancer-Specific Loss of Urocortin3 in Human Renal Cancer.

The corticotropin-releasing hormone (CRH) system, its receptors corticotropin-releasing hormone receptor 1 (CRHR1) and 2 (CRHR2), and its corresponding binding protein corticotropin-releasing hormone-binding protein (CRHBP) as well as the urocortin proteins-structural homologues to CRH, which are included in this peptide family-have become interesting oncological targets recently. Carcinogenesis of various human tumors has been reported with an altered presence of members of this system. The aim of the present study was to examine the role of urocortin3 (UCN3) in renal cell carcinoma (RCC). Therefore, tumoral tissues of 106 patients with RCC and available corresponding normal tissues were analyzed using qPCR for quantitative mRNA expression analysis. Tissue localization and protein signals of UCN3 in normal and tumoral renal specimens were evaluated using western blot and immunohistochemistry. In addition, correlation studies of UCN3 mRNA expression with clinicopathological parameters of patients with RCC and different histological subtypes were evaluated. UCN3 mRNA was significantly downregulated in nearly all tumoral tissues (p = 7.92 × 10-13). The same effect was observed at protein level using immunohistochemistry. Level of UCN3 mRNA expression was not directly correlated with clinicopathological parameters. We report for the first time the significant downregulation of UCN3 in RCC. These results demonstrate a possible involvement of the CRH system and its significance in carcinogenesis of RCC.

LC-MS based metabolomic profiling for renal cell carcinoma histologic subtypes

Renal cell carcinomas (RCC) are classified according to their histological features. Accurate classification of RCC and comprehensive understanding of their metabolic dysregulation are of critical importance. Here we investigate the use of metabolomic analyses to classify the main RCC subtypes and to describe the metabolic variation for each subtype. To this end, we performed metabolomic profiling of 65 RCC frozen samples (40 clear cell, 14 papillary and 11 chromophobe) using liquid chromatography-mass spectrometry. OPLS-DA multivariate analysis based on metabolomic data showed clear discrimination of all three main subtypes of RCC (R2 = 75.0%, Q2 = 59.7%). The prognostic performance was evaluated using an independent cohort and showed an AUROC of 0.924, 0.991 and 1 for clear cell, papillary and chromophobe RCC, respectively. Further pathway analysis using the 21 top metabolites showed significant differences in amino acid and fatty acid metabolism between three RCC subtypes. In conclusion, this study shows that metabolomic profiling could serve as a tool that is complementary to histology for RCC subtype classification. An overview of metabolic dysregulation in RCC subtypes was established giving new insights into the understanding of their clinical behaviour and for the development of targeted therapeutic strategies.

The Cancer Genome Atlas of renal cell carcinoma: findings and clinical implications.

The Cancer Genome Atlas (TCGA) characterized the somatic genetic and genomic alterations in renal cell carcinoma (RCC) encompassing the major RCC histological subtypes, including clear cell RCC (ccRCC), papillary RCC (pRCC) and chromophobe RCC (chRCC). Unique distinguishing features were found between the RCC subtypes, including in chromosomal alterations and tumour metabolism, as well as within each RCC subtype, of which some correlated with differences in patient survival. Two new RCC subtypes were defined by distinct epigenetic and metabolic pathway expression patterns, the hypermethylated CpG island methylator phenotype-associated (CIMP) RCCs and metabolically divergent chRCCs, and new biomarkers of poor patient outcome were identified, including PBRM1 mutation in type 1 pRCC and CDKN2A loss in chRCC. Expression of many immune cell gene-specific signatures was increased in ccRCC compared with pRCC and chRCC, and expression of select signatures, including the type 2 T helper cell signature, was increased in CIMP RCC. Increased expression of the type 2 T helper cell signature correlated with poorer survival in ccRCC, pRCC and chRCC. In addition to improving our current understanding of RCC, TCGA RCC studies are an invaluable resource that provides the foundation for the development of improved methods for diagnosis, treatment and prevention of this disease.

Renal cell carcinoma histological subtypes and ethnicity in New Zealand: a regional study

Renal cell carcinoma histological subtypes and ethnicity in New Zealand: a regional study

CD105 as a tool for assessing microvessel density in renal cell carcinoma.

Angiogenesis plays an essential role in both tumor growth and metastasis. CD105 expression was correlated with prognosis in many tumors, but its value in renal cell carcinoma (RCC) is still questionable. The aim of this study was to evaluate microvessel density (MVD) by using CD105 marker, in 95 cases of renal cell carcinoma. CD105 showed positivity in 93 cases. The mean MVD value was significantly higher in clear cell carcinoma compared to papillary and chromophobe subtypes (P = 0.000). We noticed a significant correlation between MVD and ISUP grade (P = 0.007). The highest MVD value was observed in tumors with ISUP grade 1 and 2, while the lowest MVD value was noted in ISUP grade 3 tumors. A high vessel density was identified in tumors with a low Fuhrman grade, compared to those with a high grade (P = 0.010). MVD value was lower in tumors with a larger diameter, compared to small ones (P = 0.026). In conclusion, CD105 expression (MVD) is inversely related to tumor aggressiveness in clear cell RCC and can be used as a favorable prognosis marker. The vascularity differences between histological subtypes of RCCs could be useful for a better selection of patients that may benefit from anti-angiogenic therapies.

19] Clinical data and outcomes of unusual variants of renal cell carcinoma at a tertiary care hospital

ObjectiveTo present our clinical data on the incidence and clinical outcomes of unusual variants of renal cell carcinoma (RCC) at a tertiary care hospital in India. RCC accounts for 2% of total cancer burden. There are several histological subtypes of RCC due to distinct molecular alterations with varied clinical outcomes. Identification of these clinical variants by further immunohistochemistry markers is required for the correct diagnosis, as each clinical subtype carries its own prognostic implication.

Imaging biomarkers based on multiphase CT data in differentiation of renal cell carcinoma

Background. Renal-cell carcinoma (RCC) is one of 10 mostly widely spread malignant tumors in the world. Recently scientists focused on investigation of new imaging biomarkers of RCC based on USG, CT, MRI and radionuclide examinations data in order to increase efficiency of current pathology diagnostics. The goal of this study was to evaluate an efficiency of application of the novel biomarkers based on multiphase CT in differential diagnostics of RCC. Materials and methods. In total 120 patients with solid renal tumors >4 cm in greatest dimension in whom nephrectomy followed by pathological analysis were enrolled into this retrospective study: 84 (70,0%) with RCC, 14 (11,67%) with transitional cell carcinoma of renal pelvis and 22 (18,33%) with benign renal tumors. We analyzed and compared pathologic and multiphase CT data. Results. Using of signal intensity with threshold 54,80 HU allowed to differentiate RCC from other renal tumors with sensitivity and specificity accordingly 98,8% and 69,4% (AUC=0,844, 95% CI=0,746–0,942, р<0,001) on excretory CT images. Differentiation of RCC and benign renal tumors using signal intensity with threshold of 61,84 HU demonstrated 79,8% sensitivity and 63,6% specificity (AUC=0,745, 95% CІ=0,599–0,891, р<0,001) on excretory CT images. Differentiation of conventional RCC histologic subtype from non-conventional using signal intensity of nephrographic CT images with threshold 79,39 HU was possible with 71,7% specificity and 54,8% sensitivity (AUC=0,718, 95% CІ=0610–0,826, р=0,001). Identification of papillary and chromophobe subtypes as well as Fuhrman grades of clear-cell RCC was also possible. Conclusions. Application of radiodensity of tumor measured using multiphase CT as diagnostic imaging biomarker of solid RCC is valuable clinical tool for differentiation of current pathology, its histologic subtypes and Fuhrman grades. The drawback of the method is relatively high radiation exposure of the patient.

Renal tumors in end-stage renal disease: A comprehensive review.

The incidence of end-stage renal disease has increased owing to the greater prevalence of patients with chronic kidney disease and diabetes mellitus. End-stage renal disease is usually accompanied by acquired cystic disease and is a risk factor for renal cell carcinoma. The present review discusses the etiology of renal cell carcinoma in end-stage renal disease patients, focusing on two unique renal cell carcinoma histological subtypes: acquired cystic disease-associated renal cell carcinoma and clear cell papillary renal cell carcinoma. Acquired cystic disease-associated renal cell carcinoma occurs almost exclusively in patients who underwent hemodialysis, especially long-term (>10years) hemodialysis. Its histology is distinctive: a cribriform or sieve-like architecture with intra- or intracystic lumina; tumor cells containing abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli; and most notably, calcium oxalate crystal deposition. Recognition of the crystals is critical for diagnosing acquired cystic disease-associated renal cell carcinoma. Acquired cystic disease-associated renal cell carcinoma typically has an indolent clinical course, except in cases with sarcomatoid components. Clear cell papillary renal cell carcinoma also has an indolent course (no cases involving metastasis have been reported to date), and its features resemble those of both clear cell renal cell carcinoma and papillary renal cell carcinoma. Unlike acquired cystic disease-associated renal cell carcinoma, which occurs only in end-stage renal disease patients, clear cell papillary renal cell carcinoma occurs in non-end-stage renal disease patients as well. Additional renal tumors in end-stage renal disease patients include anastomosing hemangiomas. Long-term hemodialysis worsens the prognosis of end-stage renal disease patients with renal cell carcinoma, regardless of its original histological subtype, presumably by inducing oxidative stress and sarcomatoid transformation.

Obesity and renal cell carcinoma risk by histologic subtype: A nested case-control study and meta-analysis

BackgroundAlthough obesity is an established risk factor for renal cell carcinoma (RCC), it is unclear whether this relationship varies across histologic subtypes. MethodsWe conducted a nested case-control study within the Kaiser Permanente Northern California (KPNC) health care network, and meta-analysis combining our results with those of previously published studies. Our KPNC study included 685 RCC cases [421 clear cell; 65 papillary; 24 chromophobe; 35 other; 141 not otherwise specified (NOS)] and 4266 controls. Subtype-specific odds ratios (ORs) and 95% confidence intervals (CIs) for categories of body mass index (BMI) and were computed from the case-control data using polytomous logistic regression. Findings from this and other relevant studies were combined by meta-analysis using a random effects model. ResultsIn the KPNC study, obesity (BMI ≥ 30 kg/m2) was associated with clear cell RCC (OR 1.5, 95% CI 1.1–2.1) and chromophobe RCC (OR 2.5, 95%CI 0.8–8.1), but not with papillary RCC (OR 1.0, 95% CI 0.5–1.9). In meta-analysis including three additional studies, a similar pattern of summary relative risks (SRR) for obesity was observed across subtypes (clear cell: SRR 1.8, 95% CI 1.5–2.2; chromophobe: SRR 2.2, 95% CI 1.3–3.7; papillary, SRR 1.2, 95% CI 0.8–1.6). ConclusionsThese findings support the hypothesis that histologic subtypes of RCC possess distinct etiologic pathways, with obesity important for the development of clear cell and, possibly, chromophobe RCC, but not papillary RCC.

Imaging and Management of Intrathoracic Renal Cell Carcinoma Metastases.

Renal cell carcinoma (RCC) has a propensity to metastasize to the chest, with the lungs being the most common distant metastatic site. The histologic subtype of RCC has implications for prognosis. Significant advances have been made in the management of metastatic RCC, both in systemic and locoregional therapies. The aim of this article is to review appearances of intrathoracic metastases from RCC and to discuss treatment considerations.

Incidence and mortality of renal cell carcinoma in the U.S.: A SEER-based study investigating trends over the last four decades.

604 Background: Renal cell carcinoma (RCC) is the third most common urologic malignancy worldwide, with clear cell subtype being the most common. In this study, we sought to investigate RCC incidence and mortality trends by demographic and tumor characteristics using data from the surveillance, epidemiology and end results (SEER) database. Methods: We used SEER database to study RCC cases between 1973 and 2014. Incidence and mortality rates were calculated by sex, age, race, state, stage, size, and histological subtype of RCC. Annual percent change (APC) was calculated using joinpoint regression software. Results: A total of 96,058 RCC cases were identified, with 54,000 RCC deaths between 1973 and 2014. Overall incidence was 9.712 per 100,000 persons-years, being highest among males (13.698), blacks (11.886), and people older than 65 years (38.693). Incidence rates of localized cases (5.845) and tumors smaller than 7 cm (6.550) were higher than other tumor subgroups with distant disease incidence of 1.773 per 100,000 persons-years. Overall incidence rates increased by 2.709% (95% CI, 2.544-2.875, p &lt; .001) per year over the study period, but rates became stable since 2007 with only an increase in the incidence of clear-cell subtype (2.538%; 95% CI, 1.300-3.791, p &lt; .001). Overall RCC mortality rates have been declining since 2000, and distant disease mortality have been decreasing since 2008 with most profound decline in the period between 2012 and 2014 with APC of -22.635% (-37.419- -4.359, P = .019) Conclusions: Despite overall increase in rates over the last 40 years, recent years have shown stable incidence and decrease in mortality rates of RCC. The significant decline in mortality over the last 10 years since the approval of the first Vascular Endothelial Growth Factor ‘VEGF’ inhibitor highlights the impact of this class of medications along with other subsequent agents such as mTOR inhibitors and checkpoint inhibitors on the prognosis of renal cell carcinoma.

Impact of histological subtype on outcomes of renal cell carcinoma patients

Background: This study aims to tackle the impact of histological subtype on the presentation and treatment trends of renal cell carcinoma (RCC).Methods: RCC cases, diagnosed from 2001 to 2013, were assembled from the Surveillance, Epidemiology and End Results (SEER) database. The incidence of different RCC histological subtypes (clear cell, papillary, chromophobe and collecting duct) was assessed and Join-Point analysis was conducted. Relevant clinicopathological characteristics were assessed and correlated with subtypes through chi-square testing. Survival analysis was then evaluated using Kaplan–Meier analysis and multivariate analyses for factors affecting overall and cancer-specific survivals were assessed.Results: A total of 89,968 RCC patients were evaluated. The incidence of different RCC subtypes has increased during the study period. Chromophobe subtype seems to have the best overall and cancer-specific survivals, whilst collecting duct subtype has the worst outcomes (p < .0001 for all endpoints). Multivariate analysis for factors affecting overall survival among non-metastatic RCC patients showed that the following factors are associated with worse overall survival (collecting duct carcinoma histology, older age, T4 disease, N2 disease, no receipt of local treatment, black race, male gender and unmarried status) (p < .0001 for all parameters).Conclusion: This analysis suggests that the prognosis of RCC varies widely according to the histological subtype. Biology-oriented preclinical and clinical assessments of novel therapeutics are needed particularly for non-clear cell RCC.

Increased expression of CD44 is associated with more aggressive behavior in clear cell renal cell carcinoma.

Although CD44 has been suggested as a prognostic marker in renal cell carcinoma (RCC), the prognostic significance of this marker in three main subtypes of RCC is still unclear. Thus, the present study was conducted to evaluate the expression and prognostic significance of CD44 as a cancer stem cell marker in different histological subtypes of RCC. Methodology & results: CD44 expression was evaluated in 206 well-defined renal tumor samples using immunohistochemistry on tissue microarrays. Higher CD44 expression was associated with more aggressive behavior, tumor progression and worse prognosis in clear cell RCC (ccRCC) but not in papillary and chromophobe RCC subtypes. Cancer stem cell marker CD44 may be a promising target for cancer treatment only in ccRCC.

The role of miRNA-15a in diagnostics of renal cell carcinoma

Renal cell carcinoma (RCC) – is the most common primary tumor of the kidney. The part of nondiagnostic percutaneous core biopsy (PCB) of the kidney varies from 5 to 40%. The application of imaging methods of examination, such as CT or MRI don’t guarantee 100% sensitivity and specificity for diagnosis of RCC, remaining within 88–96%. The objective: the goal of the investigation was to estimate the value of application of the miRNA-15a expression in urine as a biomarker of RCC. Patients and methods. The study enrolled 67 adult patients with solid renal neoplasms: RCC (n=58), benign renal tumors (n=15). The medium age was 60,19±6,36 years, the medium size of the tumor was 7,01±2,08 sm. All patients were treated by surgery. One day before and after the 8th day after the surgery in all patients and once in 30 healthy volunteers without renal pathology 100–150 ml of urine was collected with further definition of expression by using reverse transcription and PCR in real time. Results. For the first time significant difference (р<0,05) was detected between medium values of miR-15a expression in urine of the patients with RCC, benign renal tumors and healthy people: 2,50E-01±2,72E-01 УО vs 1,32E-03±3,90E-03 vs 3,36E-07±1,04E-07 УО accordingly. The strong correlation between the size of RCC and the level of miR-15a expression was observed (r=0,87). The sensitivity and specificity during differentiation of RCC and benign renal tumors using the threshold 03±5,18E-03 УО were 98,1% and 100% accordingly. Conclusion. Application measured in urine miR-15a expression may be used as a biomarker of RCC. Further studies are required with inclusion of bigger quantity of patients with different histological subtypes of RCC and grades of differentiation, benign renal tumors for more depth analysis of diagnostic value of miR-15a Further studies are needed for finding out the reason of miR-15a upregulation in urine of the patients with RCC, considering its tumor-protective features, which are described in literature.

Cytoplasmic expression of CD133 stemness marker is associated with tumor aggressiveness in clear cell renal cell carcinoma

Prominin-1 (CD133) is one of the most commonly used markers for cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CSCs in renal cell carcinoma (RCC) remains unclear. The aim of this study was to investigate the expression patterns and prognostic significance of the cancer stem cell marker CD133 in different histological subtypes of RCC. CD133 expression was evaluated using immunohistochemistry in 193 well-defined renal tumor samples on tissue microarrays, including 136 (70.5%) clear cell renal cell carcinomas (CCRCCs), 26 (13.5%) papillary RCCs, and 31 (16.1%) chromophobe RCCs. The association between CD133 expression and clinicopathological features as well as the survival outcomes was determined. There was a statistically significant difference between CD133 expression among the different RCC subtypes. In CCRCC, higher cytoplasmic expression of CD133 was significantly associated with increase in grade, stage, microvascular invasion (MVI) and lymph node invasion (LNI), while no association was found with the membranous expression. Moreover, on multivariate analysis, TNM stage and nuclear grade were independent prognostic factors for overall survival (OS) in cytoplasmic expression. We showed that higher cytoplasmic CD133 expression was associated with more aggressive tumor behavior and more advanced disease in CCRCC but not in the other examined subtypes. Our results demonstrated that higher cytoplasmic CD133 expression is clinically significant in CCRCC and is associated with increased tumor aggressiveness and is useful for predicting cancer progression.

Renal cell carcinoma histological subtype distribution differs by age, gender, and tumor size in coastal Chinese patients.

The distribution pattern of renal cell carcinoma (RCC) histological subtypes according to age, gender and tumor size has not been well illustrated in RCC patients living in fast-developing regions of China. We recruited 2941 patients with clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (PCC) or chromophobe from two hospitals in coastal China (2004−2012) consecutively and draw 538 American Chinese RCC patients’ data with time matched from the Surveillance, Epidemiology, and End Results database. We found that compared with ccRCC patients, chromophobe patients were more likely to be female (OR: 2.538, 95% CI: 1.923−3.350), younger (OR for 51−60 years old: 0.686; OR for over 60 years old: 0.478; reference: age < 50) and to have a larger maximal diameter (Dmax) (OR for Dmax > 7 cm: 1.883; reference: Dmax ≤ 4 cm). Besides, in comparison with coastal Chinese patients, American Chinese individuals had lower Fuhrman grades (P < 0.001) and had an onset age 10 years delay. In conclusion, we were the first to observe marked gender, age and tumor size differences in the proportional subtype distribution of RCCs in coastal Chinese patients, and also the first to compare coastal Chinese with American Chinese data.

GC-MS metabolomics-based approach for the identification of a potential VOC-biomarker panel in the urine of renal cell carcinoma patients.

The analysis of volatile organic compounds (VOCs) emanating from biological samples appears as one of the most promising approaches in metabolomics for the study of diseases, namely cancer. In fact, it offers advantages, such as non‐invasiveness and robustness for high‐throughput applications. The purpose of this work was to study the urinary volatile metabolic profile of patients with renal cell carcinoma (RCC) (n = 30) and controls (n = 37) with the aim of identifying a potential specific urinary volatile pattern as a non‐invasive strategy to detect RCC. Moreover, the effect of some confounding factors such as age, gender, smoking habits and body mass index was evaluated as well as the ability of urinary VOCs to discriminate RCC subtypes and stages. A headspace solid‐phase microextraction/gas chromatography–mass spectrometry‐based method was performed, followed by multivariate data analysis. A variable selection method was applied to reduce the impact of potential redundant and noisy chromatographic variables, and all models were validated by Monte Carlo cross‐validation and permutation tests. Regarding the effect of RCC on the urine VOCs composition, a panel of 21 VOCs descriptive of RCC was defined, capable of discriminating RCC patients from controls in principal component analysis. Discriminant VOCs were further individually validated in two independent samples sets (nine RCC patients and 12 controls, seven RCC patients with diabetes mellitus type 2) by univariate statistical analysis. Two VOCs were found consistently and significantly altered between RCC and controls (2‐oxopropanal and, according to identification using NIST14, 2,5,8‐trimethyl‐1,2,3,4‐tetrahydronaphthalene‐1‐ol), strongly suggesting enhanced potential as RCC biomarkers. Gender, smoking habits and body mass index showed negligible and age‐only minimal effects on the urinary VOCs, compared to the deviations resultant from the disease. Moreover, in this cohort, the urinary volatilome did not show ability to discriminate RCC stages and histological subtypes. The results validated the value of urinary volatilome for the detection of RCC and advanced with the identification of potential RCC urinary biomarkers.

Role of Computed Tomography in the Pre operative Diagnosis of Clear Cell Renal Carcinoma

Background: Renal cell carcinoma (RCC) accounts for 3% of all human malignant tumors. The behavior of RCC apparently depends on its subtype. CT scan can provide detailed information about the tumor itself and regarding its precise extension. The pre-histological diagnosis of clear cell renal carcinoma could be made with more precision on the basis of CT scan features and would ultimately play a major role in the prognosis and management of the disease. Objective: To determine the diagnostic accuracy of computed tomography in the diagnosis of clear cell renal carcinoma taking histopathological findings as gold standard. Methods: Total 100 patients had renal mass were included. All patients underwent contrast enhanced CT scan. On the basis of CT scan features a pre-surgical diagnosis of histological subtype of RCC, clear cell renal carcinoma was made. The patients were followed by nephrectomy. The diagnostic accuracy of CT scan was determined. Results: The male to female ratio was 3.2:1.0. Out of total study subjects 85.0% patients turned out to be renal cell carcinomas and among these 40 (47%) were right sided and 45 (53%) were left sided. The mean size of tumor was 12.75 cm. The sensitivity, specificity, and diagnostic accuracy of CT scan were 89.0%, 72.7%, and 86.0% respectively. Conclusion: The CT scan was helpful in diagnosing clear cell renal carcinoma. The most valuable parameter was the degree of enhancement of clear cell renal carcinoma with other parameters playing supplemental role.