Indicators In Renal Cell Carcinoma Research Articles

Low ASH1L Expression as Potential Diagnostic and Prognostic Biomarker for Renal Cell Carcinoma

As an important methyltransferase, ASH1L played main roles in cell differentiation, embryonic development and autoimmune response. It had been reported that its abnormal expression was closely related to the progression of some diseases. In the current study, we found that ASH1L was low expressed in renal cell carcinoma, and its low expression was positively correlated with tumor progression. Patients with low ASH1L expression had poor OS and RFS, and it had excellent clinical diagnostic value. Furthermore, lower ASH1L expression in dead than survival patients, and multivariate regression Cox analysis confirmed that low ASH1L expression was a predictor for poor prognosis of patients with renal cell carcinoma. Gene-set-enrichment-analysis showed that the DNA-repair, reactive-oxygen-species pathway and Myc-target V2 signaling were significantly enriched to the low ASH1L expression phenotype. Taking together, our findings demonstrated that the low ASH1L expression was likely to be useful as a promising prognostic indicator for renal cell carcinoma.

Pinin acts as a poor prognostic indicator for renal cell carcinoma by reducing apoptosis and promoting cell migration and invasion.

Pinin (PNN) was originally characterized as a desmosome‐associated molecule. Its function and the mechanism of its regulation in renal cell carcinoma (RCC) are still undefined. Data on PNN expression, clinicopathological features, and prognosis of patients with RCC were obtained from The Cancer Genome Atlas (TCGA) database. Immunohistochemistry revealed high PNN expression in tumour cells. PNN expression showed negative correlation with survival in patients with RCC, acting as an independent prognostic factor in RCC. PNN up‐regulation might be attributed to epigenetic alterations in RCC. Immunofluorescence revealed PNN expression mainly in the nucleus of RCC cells. The transfection of siRNA targeting the PNN gene resulted in enhanced apoptosis, which was detected by flow cytometry, and reduced cell migration and invasion, which were assessed using wound healing and transwell migration assay. Gene set enrichment analysis revealed associations between PNN expression and several signalling pathways involved in cancer progression, as a potential mechanism underlying the carcinogenicity of PNN. The analyses of the Tumor Immune Estimation Resource platform showed significant positive associations between high PNN expression and tumour immune infiltrating cells. PNN may function as an oncogenic factor by reducing apoptosis and promoting cell migration and invasion in RCC.

Prognostic biomarkers in renal cell carcinoma: is there a relationship with obesity?

Obesity is a recognized risk factor for renal cell carcinoma (RCC) the commonest form of kidney cancer. Both obesity and RCC are serious diseases with increasing incidence yearly. This review examined certain obesity associated measurements and adipokines as detection/prognostic indicators for RCC. The obesity related measurements such as body mass index (BMI), waist circumstance (WC), waist-hip ratio (WHR) in predicting RCC are valid when used in conjunction with other risk factors such as age and sex or with histological findings. The adipokine adiponectin holds promising outcomes as a predictive marker in assessing the risk of developing RCC. In addition, tissue leptin/leptin receptor may be a distinguishing marker for RCC subtypes. However, circulating leptin may not be a suitable detection or prognostic biomarker for RCC. The other less investigated adipokines; omentin, visfatin, apelin and resistin are also expressed in RCC but their prognostic capabilities are still inconclusive. BMI, WC and adipokines may be useful additions in a nomogram which includes TNM staging and pathological grading system to detect, confirm and follow-up RCC cases.

MP19-04 ELEVATED CD36 EXPRESSION CORRELATES WITH INCREASED VISCERAL ADIPOSE TISSUE AND PREDICTS POOR PROGNOSIS IN CCRCC PATIENTS PROGNOSIS IN CCRCC PATIENTS

INTRODUCTION AND OBJECTIVES:Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose abs...

Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients.

571 Background: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients. Methods: Real-Time qPCR was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by MRI. Pearson’s correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Cox regression analysis were developed to address the influence of independent factors on prognostic value. Gene Set Enrichment Analysis (GSEA) was performed to select related genes and pathways from TCGA database. Results: In the current study, we demonstrated that CD36 mRNA was highly expressed in ccRCC tissues, and was found significantly increased in patients with advanced TNM stage ( p= 0.003, p< 0.001, p< 0.001), and high VAT% ( p= 0.004). Pearson’s correlation coefficient indicated CD36 amplification positively correlated with BMI ( r= 0.117, p= 0.025), VAT% ( r= 0.465, p< 0.001), while negatively with SAT ( r= -0.296, p= 0.002). Furthermore, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with HR of 4.873 (3.300-7.196, p< 0.001) and 4.610 (2.956-7.189, p< 0.001). In 104 cases whose MRI scans were available, VAT was significantly correlated with poor PFS and OS. Significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, angiogenesis and TGF-β signaling pathways. Conclusions: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.

Elevated CD36 expression correlates with increased visceral adipose tissue and predicts poor prognosis in ccRCC patients.

Objective: Growing evidence has proved obesity one of the confirmed important etiologic indicators for renal cell carcinoma (RCC). CD36 is underpinned to be involved in adipose absorption, but its role in clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to investigate the mRNA expression of CD36 in anthropometric measures of adipose tissue and defining its value in predicting prognosis in ccRCC patients.Methods: Real-Time qPCR gene expression analysis was detected from 367 paired ccRCC and adjacent normal tissues. Distributions of categorical clinical-pathological data together with levels of CD36 expression were compared with χ2-test in a contingency table. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured by magnetic resonance imaging (MRI) and identified at the level of the umbilicus. Pearson's correlation coefficient was utilized to quantify relations between body mass index (BMI), VAT%, SAT and CD36 expression respectively. Partial likelihood test from univariate and multivariate Cox regression analysis were developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan-Meier method and log-rank test were performed to assess the survival benefits between discrete levels.Results: In the current study, CD36 mRNA was demonstrated highly expressed in ccRCC compared with normal tissues. In addition, CD36 mRNA expression was significantly increased in patients with advanced TNM stage (p=0.003, p<0.001, p<0.001), and high VAT% (p=0.004). Pearson's correlation coefficient indicated that CD36 amplification positively correlated with BMI (r=0.117, p=0.025), VAT% (r=0.465, p<0.001), while negatively associated with SAT (r=-0.296, p=0.002). Median PFS was 60 months and OS was 99 months. Meanwhile, ccRCC patients with elevated CD36 expression held shorter PFS and OS, with hazard ratios [HR; 95% confidence interval (CI)] of 4.873 (3.300-7.196, p<0.001) and 4.610 (2.956-7.189, p<0.001). In 104 cases with available MRI scans, VAT was significantly correlated with poor PFS and OS, with HR of 2.556 (1.036-6.310, p<0.042) and 3.291 (1.034-10.477, p<0.044). A total of 100 significant genes were obtained from GSEA, and CD36 was found involved in the most significant pathways including fatty acid metabolism, UV response, angiogenesis and transforming growth factor beta (TGF-β) signaling pathways.Conclusion: In conclusion, our study first reveal that elevated CD36 mRNA expression is positively correlated to distribution of abdominal adipose, particularly VAT%, which, in addition, notably predicts poor prognosis in ccRCC patients.

RUNX3 regulates renal cell carcinoma metastasis via targeting miR-6780a-5p/E-cadherin/EMT signaling axis.

Runt-related transcription factor 3 (RUNX3) is a tumor suppressor in many human solid tumors. In this study, renal cell carcinoma (RCC) microarray analysis showed that the level of RUNX3 expression was lower in RCC tissue than in adjacent normal renal tissues, and was correlated with depth of invasion (pT stage) (P<0.001) and Tumor Node Metastasis (TNM) stage (P<0.001). RUNX3 expression was negatively correlated with poor 5-year overall and disease-free patient survival. RUNX3 suppressed RCC metastasis and invasion and increased levels of E-cadherin, an important marker of epithelial-mesenchymal transition, in vitro and in vivo. RUNX3 also inhibited microRNA-6780a-5p, which directly targeted the E-cadherin 3’untranslated region and decreased its expression. We confirmed that miR-6780a-5p mimics abrogated RUNX3-mediated E-cadherin upregulation and RCC metastasis/invasion inhibition. Thus, RUNX3 targeted the miR-6780a-5p/E-cadherin/EMT signaling axis to suppress renal carcinoma cell migration and invasion. This pathway illustrates a new RUNX3 function and provides potential targets for the treatment of RUNX3 mutant and loss-of-function RCC tumors. RUNX3 may also act as an effective prognostic indicator in RCC.

Rap2a serves as a potential prognostic indicator of renal cell carcinoma and promotes its migration and invasion through up-regulating p-Akt

Rap2a, a member of the small GTPase superfamily, belongs to Ras superfamily, and its function in cancer progression is still poorly understood. Our previous study indicated that the ectopic expression of Rap2a enhanced the migration and invasion ability of lung cancer cells. However, its expression and molecular mechanism on renal cell carcinoma (RCC) have not been characterized. This study explored the clinical significance and biological function of Rap2a in human RCC. The clinical relevance of Rap2a in RCC was evaluated by immunohistochemical staining using tissue microarray. Our data showed that Rap2a expression was dramatically increased in RCC tissues compared with normal renal tissues. The ectopic expression of Rap2a enhanced the migration and invasive ability of cancer cells. In contrast, downregulation of Rap2a inhibited cell invasion. Rap2a had no effect on the proliferation of RCC cell lines. Meanwhile, Rap2a can regulate the phosphorylation level of Akt in vitro. In vivo studies also showed that Rap2a positively regulated metastasis of renal cancer cells and the expression of p-Akt. These findings indicate that Rap2a promotes RCC metastasis and may serve as a candidate RCC prognostic marker and a potential therapeutic target.

Reply by Authors

No AccessJournal of UrologyAdult Urology1 Apr 2017Reply by Authors View All Author Informationhttps://doi.org/10.1016/j.juro.2016.10.130AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Reply by Authors." The Journal of Urology, 197(4), p. 997 References 1 : Multilocular cystic renal cell carcinoma: comparison of imaging and pathologic findings. AJR Am J Roentgenol2012; 198: W20. Google Scholar 2 : Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma. Mod Pathol2010; 23: 931. Google Scholar 3 : Significance of macroscopic tumor necrosis as a prognostic indicator for renal cell carcinoma. J Urol2006; 176: 1332. Link, Google Scholar © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 197Issue 4April 2017Page: 997 Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.MetricsAuthor Information Expand All Advertisement PDF downloadLoading ...

Reporting on quality indicators in renal cell carcinoma: Proportion of metastatic patients who initially commence on full-dose targeted therapy.

265 Background: Measuring quality of care is required to improve patient outcomes. There are 23 established Quality Indicators in Renal Cell Carcinoma (RCC) (Wood LA et al, JOP 2013) including initiating targeted therapy (TT) at full dose. It is recognized that the dose of TT is important to optimize clinical outcomes. Methods: The Canadian Kidney Cancer Information System (CKCis) is a prospectively maintained database of RCC pts from 14 Canadian academic centers. CKCis data was used to determine the use of TT in metastatic pts, the initial dose in the first line setting, and factors influencing whether pts initiated full dose TT. Descriptive statistics were performed to characterize current practices and a multivariate logistic regression was performed to assess predictors of initiating full dose TT. Results: Between 2006 and 2014, 560 pts received first-line TT and make up the study cohort. 92% received VEGF TT (81% sunitinib; 9% pazopanib; 2% sorafenib) and 8% received mTOR TT (5% everolimus; 3% temsirolimus). All pts receiving mTOR inhibitors received full dose and are excluded from further analysis. Full dose VEGF TT was initiated in 87% on sunitinib, 78% on pazopanib, and 92% on sorafenib. The sunitinib schedule was 4/2 in 81%, 2/1 in 12%, and other in 7%. Pts were less likely to initiate full dose TT if they were older (OR: 1.10, 95% CI 1.06-1.15), female (OR: 2.23, 95% CI 1.09-4.55) or had a worse ECOG PS (2,3,4 vs 0,1) (OR: 2.30, 95% CI 0.95-5.59). Data on initial versus final dose of TT will also be presented. Conclusions: Maximizing exposure to TT is important in metastatic RCC which is why initiating full dose TT was prioritized as a key QI in RCC. In this study, 87% of pts were initiated on full dose VEGF TT in the first line setting, and 100% of pts on mTOR TT which is higher than predicted. Those less likely to start on full dose VEGF TT were older, female and had a lower ECOG PS. The gender discrepancy will be explored in future studies.

Using the Delphi Technique to Improve Clinical Outcomes Through the Development of Quality Indicators in Renal Cell Carcinoma

Optimal quality of care is needed for ideal outcomes. In renal cell carcinoma (RCC), there is a lack of information defining optimal care. This is particularly important in RCC, with increased complexity of care and a need for coordination among providers. The goal of this study was to identify quality indicators (QIs) and measures of quality care across the RCC disease spectrum. A modified Delphi technique was used to select QIs that are relevant and practical to RCC care. This technique involved an expert panel of 13 urologic and medical oncologists who participated in two e-mail questionnaires and an in-person meeting to review and prioritize potential QIs. These potential QIs were identified from a systematic literature review or were suggested by panel members. From 233 literature citations, 34 possible QIs were identified; 24 additional potential QIs were suggested. A final set of 23 QIs was established. These are distributed across the RCC disease spectrum as follows (number of QIs in parentheses): screening (n=1), diagnosis/prognosis (n=3), surgical for localized disease (n=6), surgery for advanced disease (n=3), systemic therapy (n=6), and follow-up (n=2). In addition, two QIs related to survival outcomes (overall and progression-free survival) were selected. A systematic, consensus-based approach was used to determine relevant QIs in RCC care. These 23 QIs will provide a means of evaluating the quality of RCC care in an effort to improve outcomes in patients. The next step will be to establish a means of measuring each QI based on defined or yet-to-be-defined benchmarks.

626 PROGNOSTIC SIGNIFICANCE OF EXTENT OF RENAL VEIN INVOLVEMENT IN RENAL CELL CARCINOMA TREATED WITH RADICAL OR PARTIAL NEPHRECTOMY: EVIDENCE TO SUPPORT SUB-STRATIFICATION OF AMERICAN JOINT COMMITTEE ON CANCER T3A STAGE CLASSIFICATION

INTRODUCTION AND OBJECTIVES: Patients with renal call carcinoma (RCC) tumor thrombus, have a broad range of survival, with a review reporting 5-year survival between 32% and 69% (Lawindy et al 2012). Controversy exists regarding which features are prognostic indicators in renal cell carcinoma. The American Joint Committee on Cancer (AJCC) and the Union International Centre le Cancer (UICC) modified the RCC staging system in 2010 (7th edition) to further differentiate renal vein involvement from inferior vena cava involvement. The current staging labels T3a as invasion into the renal vein or segmental (muscle containing) branches, T3b into the inferior vena cava below the diaphragm, and T3c into the vena cava above the diaphragm or into the wall of the vena cava. However, the staging does not differentiate between the extent of renal vein invasion. The objective of this study was to examine the prognostic significance of the degree of tumor thrombus invasion into branches of renal vein versus main renal vein. METHODS: We performed a retrospective review of our comprehensive cancer centerAEs database, identifying 129 patients with renal cell carcinoma with tumor thrombus extension into the renal vein that underwent radical or partial nephrectomy between 1990 and 2012. The patients were classified as having tumor extension into the main renal vein or segmental muscle containing branches of the renal vein. RESULTS: Ninety-two patients were classified as main renal vein and 37 were classified as segmental. On cox regression analysis segmental versus main renal vein was compared for disease specific and overall survival. Disease specific survival was significantly worse for main renal vein than segmental with a p value of 0.0351. Overall survival was not significant with a p value of 0.109. On multivariate analysis, controlling for pathology grade and tumor maximum diameter disease specific survival was still significantly worse for main renal vein than segmental with a p value of 0.043, and overall survival was again not statistically significant with a p value of 0.144. CONCLUSIONS: These findings suggest that the level of tumor thrombus within the renal vein has prognostic implications. This data supports the idea that the tumor staging guidelines should be further modified to take into account the degree of renal vein invasion.

Fuhrman Grade Provides Higher Prognostic Accuracy Than Nucleolar Grade for Papillary Renal Cell Carcinoma

Recent evidence suggests that nucleolar grade but not Fuhrman grade is applicable to papillary renal cell carcinoma. We tested this hypothesis in an independent large series from a single institution. One dedicated uropathologist regraded 158 cases of papillary renal cell carcinoma by nucleolar and Fuhrman grades. The prognostic value and predictive accuracy of these grading systems to predict disease specific survival were analyzed by Cox proportional hazards models and the concordance index. There were 39 papillary renal cell carcinoma related deaths (25%) at a mean followup of 50 months. On univariate analysis nucleolar grade predicted disease specific survival with a concordance index of 67.8% but the survival difference between grades 1 and 2 did not attain statistical significance (p = 0.1441). Fuhrman grade predicted disease specific survival significantly better (concordance index 74.7%, p <0.001). Comparison of survival estimates between the grades revealed statistical significance across each grade category (each p <0.05). Fuhrman but not nucleolar grade was retained as an independent prognostic factor on multivariate analysis (p = 0.027 and 0.128, respectively). Each grading system performs well but the predictive accuracy of Fuhrman grade is statistically superior to that of nucleolar grade and only Fuhrman grade provides independent prognostic information on patients with papillary renal cell carcinoma. Thus, Fuhrman grade should be the standard grading system for papillary renal cell carcinoma.

Pathological prognostic indicators in renal cell carcinoma

ObjectiveTo analyze histological factors not routinely assessed as potential prognostic factors in renal cell carcinoma, such as tumor necrosis, microscopic vascular invasion, and sinus fat invasion. Materials and methodsA retrospective, analytical study was conducted of surgical specimens from 139 patients with localized renal cell carcinoma who underwent nephrectomy from 1993 to 2005. Tumor necrosis, microscopic vascular invasion, and sinus fat invasion were analyzed and compared to the classical factors: TNM classification, Fuhrman grade, and tumor size. For statistical analysis, variables analyzed were categorized as pT1, 2 vs pT3, 4; Fuhrman grade 1, 2 vs 3, 4; tumor size <7cm vs ≥7cm; tumor necrosis vs no tumor necrosis; microvascular invasion of sinus fat vs no invasion. Cancer-specific survival probability and disease-free survival were calculated. A descriptive and analytical statistical analysis was performed using logistic regression for univariate and multivariate analyses. Dependent variables were used to analyze cancer-specific survival rates. Disease-free survival was estimated using a Cox regression model and Kaplan-Meier curves. ResultsIn the univariate analysis, all variables analyzed had a significant influence on death for renal cell carcinoma. In the multivariate analysis, the variable having the greatest influence was Fuhrman grade (p=0,032). The variables significantly influencing disease-free survival, estimated by the Cox method, were the pT stage (p=0.038) and Fuhrman grade (p=0.048). ConclusionsIn patients with clinically localized renal cell carcinoma undergoing nephrectomy, pT stage and Fuhrman grade are the most important prognostic factors for survival and disease-free survival. Tumor necrosis, microscopic vascular invasion, and sinus fat invasion are prognostic factors for death from renal carcinoma which are associated to TNM classification, Fuhrman grade, and tumor size

High nuclear Livin expression is a favourable prognostic indicator in renal cell carcinoma

To assess the protein expression of Livin, an apoptosis inhibitor, in renal cell carcinoma (RCC) and to determine its prognostic relevance. Immunohistochemical staining for Livin was performed in tissue microarrays (TMAs), including tumour tissue cores, from patients with RCC who had undergone renal surgery. In 682 TMAs cytoplasmatic staining intensity and nuclear staining quantity were evaluated, and the association of Livin expression with progression-free survival (PFS) and cancer-specific survival (CSS) was analysed with a multivariate Cox regression model. Over a median (range) follow-up of 5.2 (0-16.1) years, 204 patients (28%) had died from their disease. The CSS rates at 1 and 5 years for the entire cohort was 88% and 71%. Cytoplasmatic Livin staining was absent in 516 (76%) specimens; staining was positive in 166 (24%) specimens. Weak nuclear Livin staining (<or=25%) was present in 571 (84%) specimens, strong nuclear staining (26-100%) in 111 (16%). In multivariate analysis, high (>25%) nuclear Livin expression was a favourable independent predictor of PFS and CSS even after adjusting for tumour stage, Fuhrman grade, age, sex and Karnofsky severity rating. Cytoplasmatic Livin expression did not offer additional prognostic information. High nuclear Livin expression is a favourable independent predictor of PFS and CSS in patients with RCC.

Microvascular Tumor Invasion, Tumor Size and Fuhrman Grade: A Pathological Triad for Prognostic Evaluation of Renal Cell Carcinoma

The biological behavior and clinical outcome of renal cell carcinoma are difficult to predict. We investigated the prognostic impact of clinicopathological variables to establish a risk stratification model to predict recurrence and survival rates. We studied 230 patients with renal cell carcinoma (stages T(1-4) N(x) M(0)) who underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 48 months (range 3 to 140). Univariate and multivariate analyses were performed, and the influence of clinical presentation, histological tumor size, tumor grade, lymph node involvement and microvascular tumor invasion on disease-free and cancer specific survival curves was determined. A composition model based on independent prognostic variables was then created to stratify tumors into low, intermediate and high risk of progression. The tumor recurrence rate was 17% (39 of 230) and the cancer specific mortality rate was 13% (31 of 230). Multivariate analyses determined that microvascular tumor invasion, tumor grade and tumor size were the only independent prognostic factors. Disease-free survival rates for low, intermediate and high risk tumors were 94.7%, 56.8% and 13.1%, respectively. Cancer specific survival rates were 94.7%, 61.7% and 32.0%, respectively. Tumor size, Fuhrman grade and microvascular tumor invasion are strong and independent predictors of survival of patients with renal cell carcinoma. Risk assessment and stratification based on this triad of pathological features may allow better individualization of followup schedules and trials of adjuvant treatment for patients with renal cell carcinoma.

Tumor Size Predicts Synchronous Metastatic Renal Cell Carcinoma: Implications for Surveillance of Small Renal Masses

Active surveillance of small incidental renal masses is associated with slow radiographic growth and a low risk of metastatic progression. Radiographic tumor size, in the absence of histological data, is the only prognostic indicator available when considering active surveillance. To better define the relationship between tumor size and the metastatic potential of small renal masses, we investigated whether radiographic tumor size predicts for the presence of synchronous metastases in renal cell carcinoma. We reviewed our institutional tumor registry to identify sporadic pathologically verified renal cell carcinoma treated during an 8-year period. We analyzed data regarding primary tumor size and the presence of biopsy proven synchronous metastatic disease at presentation. All N+M0 and nonpathologically confirmed M+ disease was excluded from analysis. We compared 110 cases of renal cell carcinoma with biopsy proven synchronous metastatic disease at presentation to 250 controls with clinically localized renal cell carcinoma. Tumors associated with synchronous metastasis were significantly larger than localized lesions (median 8.0 cm [range 2.2 to 20.0] vs 4.5 cm [range 0.3 to 17.5], p <0.0001). The probability of synchronous metastasis increased with increasing primary tumor size (p <0.0001). There were no patients with tumors 2 cm or smaller who presented with biopsy confirmed metastatic disease and less than 5% (5 of 110) of all synchronous metastasis occurred in tumors 3.0 cm or smaller. Logistic regression models determined that the odds of synchronous metastasis increased by 22% for each 1 cm increase in tumor size. Radiographic tumor size is a significant clinical predictor of the presence of biopsy proven synchronous metastatic renal cell carcinoma. In our series the odds of presenting with synchronous, biopsy proven metastatic disease increased by 22% with each 1 cm increase in tumor size. A 100% odds increase, or doubling of the risk of metastasis, occurs with a 3.5 cm increase in primary tumor size. These data have important implications for extent of disease evaluations in patients with large tumors and for the active surveillance of small enhancing renal masses.

Significance of Macroscopic Tumor Necrosis as a Prognostic Indicator for Renal Cell Carcinoma

We investigated the prognostic significance of macroscopic tumor necrosis in renal cell carcinoma. We retrospectively analyzed the records of 485 patients who underwent surgical treatment for organ confined or metastatic renal cell carcinoma. The presence or absence of tumor necrosis was evaluated based on macroscopic description of the tumor, and tumors were considered necrotic only if they exhibited more than 10% macroscopic necrosis. Macroscopic tumor necrosis was identified in 27% of total patients. Patients with macroscopic necrotic renal cell carcinoma were more likely to have larger tumor, metastatic disease, higher local stage and higher tumor grade (all p < 0.001). Pathological features of microvascular invasion (p = 0.026) and sarcomatoid differentiation (p = 0.002) along with several laboratory findings were also observed to be associated with macroscopic tumor necrosis. Among the total subjects those without macroscopic tumor necrosis had significantly higher progression-free (p < 0.0001) and disease specific survival (p < 0.0001). When survival analysis was limited to nonmetastatic tumors only, the same logic applied, which was not the case for the patients with metastatic disease (p > 0.05). Among the different histological subtypes of renal cell carcinoma, macroscopic tumor necrosis was observed to have a significant impact only for the clear cell subtype. In patients with nonmetastatic RCC multivariate analysis revealed that macroscopic tumor necrosis (p = 0.004) was an independent prognostic predictor of disease specific survival along with pathological T stage, tumor grade and tumor size. Our results suggest that macroscopic tumor necrosis may be a reliable prognostic indicator for nonmetastatic clear cell renal cell carcinoma which should routinely be examined for during pathological analysis.

Significance of Erythrocyte Sedimentation Rate and C-reactive Protein as Predictive Factors for Prognosis in Non-metastatic Renal Cell Carcinoma

Purpose: This study was performed to investigate the significance of preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and postoperative ESR and CRP nadir as predictive factors for prognosis in patients with non-metastatic renal cell carcinoma (RCC). Materials and Methods: In 66 patients with non-metastatic RCC for whom ESR and CRP could be measured before radical nephrectomy and during follow-up, the preoperative ESR, preoperative CRP, postoperative ESR nadir and postoperative CRP nadir were compared with the clinicopathological variables. Results: Patients with elevated preoperative ESR or CRP levels were more likely to have tumors with adverse features, including larger tumor size, higher T stage, higher nuclear grade and more frequent metastasis at follow-up, as compared to those patients with lower preoperative ESR or CRP levels, respectively. Patients with an elevated postoperative CRP nadir developed metastasis more frequently at follow-up as compared to those patients with a lower level of postoperative CRP nadir. The univariate analyses identified tumor size, T stage, preoperative ESR, preoperative CRP and postoperative CRP nadir as significant prognostic factors for recurrence-free survival. Conclusions: Elevated preoperative ESR, preoperative CRP and postoperative CRP nadir are associated with a worse prognosis and a higher recurrence rate in patients with non-metastatic RCC, suggesting that ESR and CRP are valuable prognostic indicators in RCC. (Korean J Urol 2006; 47:1059-1064) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ

Serum Amyloid A (SAA), C-reactive protein (CRP) and IL-6 as prognostic indicators in Renal Cell Carcinoma and Prostate Cancer

9711 Background: IL-6, CRP and SAA are three biomarkers whose expressions have been shown to correlate with prognosis in select tumor models. We have evaluated these three biomarkers and their potential use as prognostic indicators in renal cell carcinoma (RCC) and prostate cancer in a retrospective study. Methods: Serum samples from patients with RCC or prostate cancer were obtained from IMPATH-BCP, Inc. (New York, NY). Healthy control subjects were also included. Serum levels of IL-6, CRP and SAA were measured using commercially available ELISA kits. Summary statistics were calculated and associations between variables were evaluated using linear regression analysis and Pearson correlation coefficient. Results: Serum levels of IL-6 (range <0.78 - 175 pg/mL), CRP (range 0.74 - 144.98 μg/mL) and SAA (<9.40 - 1530.84 ng/mL) were measured. All three biomarkers were found to be significantly higher in patients with RCC, while only SAA and CRP were found to be significantly higher in PC patients when compared to normal donors. Significant correlations between IL-6, CRP, and SAA were revealed by statistical analysis of the RCC serum data (IL-6/CRP r2=0.752; SAA/CRP r2=0.596; SAA/IL-6 r2=0.635). Correlation of these markers with patient survival (defined as the number of days between date of diagnosis and date of death) was found using Pearson correlation coefficients for RCC data analysis (IL-6 -0.4151, p=0.0063; CRP –0.4129, p=0.0059; SAA –0.3793, p=0.0158). In prostate cancer patients, no correlations between PSA and SAA, or CRP and IL-6 were found. Additionally, no significant correlation was observed between the investigated markers and survival (IL-6 0.0996, p=0.4650; CRP −0.0354, p=0.8219; SAA –0.0670, p=0.6207). Conclusions: Based on these results, it appears that there may be mild to moderate association between survival time and the inflammatory markers in RCC but not in PC. However, other clinical variables may affect these conclusions in these heterogeneous populations. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Centocor, Inc. Centocor, Inc. Centocor, Inc.