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This study systematically investigates the roles of messenger RNAs (mRNAs) and microRNAs (miRNAs) in Renal Cell Carcinoma (RCC) and their potential as diagnostic and prognostic biomarkers via a stratification approach. By utilizing The Cancer Genome Atlas (TCGA) database, differentially expressed mRNAs (namely DEGs) and miRNAs (namely DEMs) are identified, and survival prognosis-related biomarkers are determined through Kaplan-Meier analysis and lasso regression. Prognostic models are established for RCC ethnicity, pathologic stages, and metastatic status, with validation through plotting risk heatmaps, risk curves, survival curves, and Receiver Operating Characteristic (ROC) curves. A total of 45 mRNA and 33 miRNA biomarkers are identified across different prognostic models, resulting in enhanced prediction accuracy with increased stratification. The literature review confirms abnormal expressions of 28 prognostic RNAs reported in experiments and 15 prognostic RNAs reported in bioinformatics studies. The study also introduces 35 novel prognostic RNAs as potential treatment targets for RCC. The mRNA+miRNA prognostic models exhibit the most robust predictive capability, indicating their potential clinical relevance. Overall, the study contributes to a precise prognosis of RCC by exploring novel biomarkers and potential therapeutic targets.

Abstract Background Growing evidence shows that ultra-processed food consumption is associated with the risk of cancer. However, prospective evidence is limited on renal cell carcinoma (RCC) incidence and mortality. In this study, we aimed to examine the association of ultra-processed food consumption and RCC incidence and mortality in a large cohort of US adults. Methods A population-based cohort of 101,688 participants were included from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed food items were confirmed by using the NOVA food classification system. The consumption of ultra-processed food was expressed as a percentage of total food intake (g/day). Prospective associations were calculated using Cox regression. Restricted cubic spline regression was used to assess nonlinearity. Subgroup analyses were performed to investigate the potential effect modifiers on the incidence and mortality of RCC. Results A total of 410 participants developed RCC during a total of 899,731 person-years of follow-up (median 9.41 years) and 230 RCC deaths during 1,533,930 person-years of follow-up (median 16.85 years). In the fully adjusted model, participants in the highest compared with the lowest quintiles of ultra-processed food consumption had a higher risk of RCC (HR quartile 4 vs 1:1.42; 95% CI: 1.06–1.91; P trend = 0.004) and mortality (HR quartile 4 vs. quartile 1: 1.64; 95% CI: 1.10–2.43; P trend = 0.027). Linear dose–response associations with RCC incidence and mortality were observed for ultra-processed food consumption (all P nonlinearity > 0.05). The reliability of these results was supported by sensitivity and subgroup analyses. Conclusion In conclusion, higher consumption of ultra-processed food is associated with an increased risk of RCC incidence and mortality. Limiting ultra-processed food consumption might be a primary prevention method of RCC.

Background: Growing evidence shows that ultra-processed food consumption is associated with the risk of cancer. However, prospective evidence is limited on renal cell carcinoma (RCC) incidence and mortality. In this study, we aimed to examine the association of ultra-processed food consumption and RCC incidence and mortality in a large cohort of US adults. Methods: A population-based cohort of 101,688 participants were included from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Ultra-processed food items were confirmed by using the NOVA food classification system. The consumption of ultra-processed food was expressed as a percentage of total food intake (g/day). Prospective associations were calculated using Cox regression. Restricted cubic spline regression was used to assess nonlinearity. Subgroup analyses were performed to investigate the potential effect modifiers on the incidence and mortality of RCC. Results: A total of 410 participants developed RCC during a total of 899,731 person-years of follow-up (median 9.41 years) and 230 RCC deaths during 1,533,930 person-years of follow-up (median 16.85 years). In the fully adjusted model, participants in the highest compared with the lowest quintiles of ultra-processed food consumption had a higher risk of RCC (HR quartile 4 vs 1:1.42; 95% CI: 1.06–1.91; Ptrend = 0.004) and mortality (HR quartile 4 vs. quartile 1: 1.64; 95% CI: 1.10–2.43; Ptrend = 0.027). Linear dose–response associations with RCC incidence and mortality were observed for ultra-processed food consumption (all Pnonlinearity > 0.05). The reliability of these results was supported by sensitivity and subgroup analyses. Conclusion: In conclusion, higher consumption of ultra-processed food is associated with an increased risk of RCC incidence and mortality. Limiting ultra-processed food consumption might be a primary prevention method of RCC. [ABSTRACT FROM AUTHOR]

Incidences of kidney cancers are steadily increasing. The surgical resection of renal tumors remains the treatment of choice, and different techniques provide similar oncological outcomes. Minimally invasive methods, especially partial nephrectomy (PN), have emerged as the preferred method of tumor resection, both in traditional and robot-assisted laparoscopy. PN may be performed as an open or laparoscopic operation. On-clamp PN is a variant of PN that includes the clamping of renal vessels; off-clamp PN is performed without any ischemia. Objectives: To assess the short-term loss of eGFR after on-clamp and off-clamp PN. Methods: Data from 2021 to 2024 were retrospectively collected from a hospital database. The patients included in the study had a diagnosed kidney tumor that was confirmed by MRI or CT imaging. The patients were divided into two groups depending on the type of treatment they received: on-clamp PN or off-clamp PN. Hematocrit (HCT), hemoglobin (Hb) and eGFR were measured and compared. Results: Both groups had comparable preoperative HTC, Hb, and eGFR. eGFR loss 24 h after the procedure was 35.4% lower in the off-clamp group compared to the on-clamp group (p = 0.027). Conclusions: Off-clamp PN is a safe and viable method for kidney tumor resection, both in traditional and robot-assisted laparoscopy. This technique results in a smaller perioperative loss of eGFR, which relates to better short-term functional outcomes than on-clamp PN. [ABSTRACT FROM AUTHOR]

Simple Summary: RCC has traditionally been considered radioresistant, with surgery being the gold standard for primary localized RCC. However, not all patients are suitable for surgery and percutaneous, non-surgical options are invasive, with significant limitations. SABR is a non-invasive advanced RT technique that delivers high doses accurately. Growing evidence supports SABR as a definitive alternative therapy for medically inoperable patients, those who decline surgery, are unfit for invasive ablation, or are at high-risk of requiring postoperative dialysis. SABR has shifted the renal radioresistance paradigm, widening the therapeutic window. Additionally, SABR is increasingly used for locally recurrent, oligoprogressive, and oligometastatic disease. This review aims to support the use of SABR across various stages of RCC disease and explore future directions. The overall landscape of RCC is promising, and we are confident that our update will stimulate further research in this field and contribute to the advancement of patient care. Renal cell cancer (RCC) has traditionally been considered radioresistant. Because of this, conventional radiotherapy (RT) has been predominantly relegated to the palliation of symptomatic metastatic disease. The implementation of stereotactic ablative radiotherapy (SABR) has made it possible to deliver higher ablative doses safely, shifting the renal radioresistance paradigm. SABR has increasingly been adopted into the multidisciplinary framework for the treatment of locally recurrent, oligoprogressive, and oligometastatic disease. Furthermore, there is growing evidence of SABR as a non-invasive definitive therapy in patients with primary RCC who are medically inoperable or who decline surgery, unsuited to invasive ablation (surgery or percutaneous techniques), or at high-risk of requiring post-operative dialysis. Encouraging outcomes have even been reported in cases of solitary kidney or pre-existing chronic disease (poor eGFR), with a high likelihood of preserving renal function. A review of clinical evidence supporting the use of ablative radiotherapy (SABR) in primary, recurrent, and metastatic RCC has been conducted. Given the potential immunogenic effect of the high RT doses, we also explore emerging opportunities to combine SABR with systemic treatments. In addition, we explore future directions and ongoing clinical trials in the evolving landscape of this disease. [ABSTRACT FROM AUTHOR]

C-Reactive Protein (CRP) is associated with diverse outcomes in patients with, or suspected to have, genitourinary malignancies. CRP levels have been shown to be associated with the probability of a prostate cancer diagnosis in patients with elevated PSA, the probability of biochemical recurrence following definitive treatment for localized prostate cancer, and decreased overall survival for patients with advanced disease. In patients with bladder and kidney cancers, CRP levels have been associated with disease progression, stage, and cancer-specific survival. Despite the abundance of correlative studies, the relationship between CRP levels and genitourinary cancer pathogenesis is not clearly understood. Here, we review the evidence for CRP as a biomarker in genitourinary (GU) cancers, with specific focus on potential clinical applications.

C-Reactive Protein (CRP) is associated with diverse outcomes in patients with, or suspected to have, genitourinary malignancies. CRP levels have been shown to be associated with the probability of a prostate cancer diagnosis in patients with elevated PSA, the probability of biochemical recurrence following definitive treatment for localized prostate cancer, and decreased overall survival for patients with advanced disease. In patients with bladder and kidney cancers, CRP levels have been associated with disease progression, stage, and cancer-specific survival. Despite the abundance of correlative studies, the relationship between CRP levels and genitourinary cancer pathogenesis is not clearly understood. Here, we review the evidence for CRP as a biomarker in genitourinary (GU) cancers, with specific focus on potential clinical applications. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Recently, long noncoding RNAs (lncRNAs) have attracted more attention for their roles in tumor progression. The aim of this study was to investigate the role of lncRNA ZFPM2 antisense RNA 1 (ZFPM2- AS1) in the progression of renal cell cancer (RCC), and to explore the possible underlying mechanism. PATIENTS AND METHODS: Expression levels of ZFPM2-AS1 in both RCC cells and 50 paired tissue samples were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the relationship between lncRNA ZFPM2-AS1 expression level and clinic- pathological characteristics as well as patients' disease-free survival rate was explored, respectively. Furthermore, cell proliferation assay, wound healing assay and transwell assay were performed to investigate the role of lncRNA ZFPM2-AS1 in vitro. In addition, Western blot assay, Luciferase reporter gene assay and RNA immunoprecipitation assay were used to explore the possible underlying mechanism. RESULTS: The expression level of ZFPM2- AS1 in tumor tissues was significantly higher than that of corresponding normal tissues. ZFPM2- AS1 expression was associated with lymph node metastasis, tumor stage and survival time of RCC patients. Moreover, the overexpression of ZFPM2-AS1 significantly promoted the growth, invasion and migration of tumor cells, whereas remarkably inhibited cell apoptosis in vitro. Further experiments revealed that miR-137 was a direct target of ZFPM2-AS1. In addition, miR-137 expression in tumor tissues was negatively correlated with ZFPM2-AS1 expression. CONCLUSIONS: Our findings indicated that ZFPM2-AS1 could promote metastasis and proliferation, whereas inhibiting the apoptosis of RCC via targeting miR-137. This study might provide a new vision for interpreting the mechanism of RCC development. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Increasing studies reported that the serum- and glucocorticoid-inducible kinases (SGKs) contributed to the tumorigenesis of various cancer. In this article, we are aiming to explore the function of SGK2 in renal cell cancer (RCC). PATIENTS AND METHODS: In this study, the SGK2 expression was quantified by Western blot (WB) in multiple RCC cell lines. And in vitro SGK2 knockdown and overexpression experiments were also performed. In addition, molecular function analysis was performed using FunRich software V3. The Cancer Genome Atlas (TCGA) database was retrieved to verify the association between the SGK2 expression and the prognosis of RCC patients. RESULTS: We found that SGK2 was up-regulated in RCC tissues compared with adjacent normal tissues, and the SGK2 expression also increased in various RCC cell lines compared to that in the normal epithelial cell line HK-2. Meanwhile, the SGK2 expression was significantly associated with the survival rate of RCC patients. Functional experiments showed that silencing SGK2 expression inhibited RCC cells proliferation, migration, colony formation and invasion abilities in vitro, whereas opposite results were uncovered after overexpressing SGK2 in RCC cells. Furthermore, functional analyses showed that SGK2 related genes were associated with protein serine/threonine kinase activity, guanosine triphosphatase (GTPase) activity, guanyl-nucleotide exchange factor activity, and motor activity. Protein interaction analysis identified that growth factor receptor-bound protein 2 (GRB2), one of the most important upstream components in the growth factor signaling pathway, was significantly enriched in SGK2 related genes. In addition, the WB assay validated that SGK2 could promote the phosphorylation of ERK 1/2 and AKT. CONCLUSIONS: Our results suggested that SGK2 promoted RCC progression by mediating the phosphorylation of extracellular regulated protein kinases (ERK) 1/2 and Protein kinase B (AKT/PKB), indicating that SGK2 might serve as a potential prognostic marker and therapeutic target for renal cancer patients. [ABSTRACT FROM AUTHOR]

Purpose: An increasing interest in percutaneous ablation of renal tumors has been caused by the increasing incidence of SRMs, the trend toward minimally invasive nephron-sparing treatments and the rapid development of local ablative technologies. In the era of shared decision making, patient preference for non-invasive treatments also leads to an increasing demand for image-guided ablation. Although some guidelines still reserve ablation for poor surgical candidates, indications may soon expand as evidence for the use of the two most validated local ablative techniques, cryoablation (CA) and radiofrequency ablation (RFA), is accumulating. Due to the collaboration between experts in the field in biomedical engineering, urologists, interventional radiologists and radiation oncologists, the improvements in ablation technologies have been evolving rapidly in the last decades, resulting in some new emerging types of ablations.Methods: A literature search was conducted to identify original research articles investigating the clinical outcomes of new emerging technologies, percutaneous MWA, percutaneous IRE and SABR, in patients with primary cT1 localized renal cell cancer.Results: Due to the collaboration between experts in the field in biomedical engineering, urologists, interventional radiologists and radiation oncologists, the improvements in ablation technologies have been evolving rapidly in the last decades. New emerging technologies such as microwave ablation (MWA), irreversible electroporation (IRE) and stereotactic ablative radiotherapy (SABR) seem to be getting ready for prime time.Conclusion: This topical paper describes the new emerging technologies for cT1 localized renal cell cancer and investigates how they compare to CA and RFA. [ABSTRACT FROM AUTHOR]

Background: Body mass index (BMI) and body composition have been associated with postoperative outcomes in oncological surgery. Evidence in renal cell cancer (RCC) is limited and inconsistent. Therefore, we examined BMI and body composition in relation to postoperative outcomes in patients with RCC., Methods: We conducted a multicenter population-based historical cohort study including 801 patients with RCC treated with radical (79%) or partial (21%) nephrectomy between 2008-2012. Computed Tomography images at third lumbar vertebrae were assessed for skeletal muscle (SM) index, SM density, visceral adipose tissue (VAT) index and subcutaneous adipose tissue index (SATI). Multivariable multilevel logistic regression analyses were used to examine associations between BMI, body composition and (major) postoperative complications and extended length of hospital stay (LOHS) (≥7 days). Discrimination of models for major complications was compared using receiver operating characteristics (ROC) curves., Results: In total, 19.6% of the patients had postoperative complications (6.2% Clavien grade ≥III) and 24.1% had extended LOHS. A 10-unit increase in SM density was inversely associated with extended LOHS [odds ratio (OR) 0.58; 95% confidence interval (95% CI): 0.44-0.78]. Associations of high BMI and lower SM density with risk of major complications and of higher VAT index with extended LOHS were also observed but statistical significance differed according to surgical procedure. Models predicting major complications with or without body composition parameters were not different., Conclusions: Lower SM density was associated with extended LOHS and non-significantly associated with higher risk of major postoperative complications. High BMI was associated with higher risk of major postoperative complications. Higher VAT was non-significantly associated with higher risk of extended LOHS. Results by surgical procedure were in the same direction but were only statistically significant for some subgroups. Validation of these results and investigation of the added value of body composition parameters to anatomic classification systems is needed., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-367/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Abstract: In recent years, a number of new molecules – commonly known as biological therapies – have been approved or are in late stages of regulatory evaluation for the treatment of advanced breast cancer. These innovative compounds have improved treatment efficacy and have probably contributed to the increase in survival length observed in some breast cancer subtypes. However, these agents are not deprived of toxicity, which can impair quality of life and may occasionally be life-threatening. In this article, we reviewed the most common toxicities associated with these drugs and provided a number of practical recommendations on their optimal clinical management. [Copyright &y& Elsevier]

Highlights: [•] First report on significant association of CYP1A1 polymorphism with idiopathic CKD. [•] Association of CYP1A1*2A and *2C hetero-/homozygous genotype combination with CKD. [•] First report of its kind on Indian population. [Copyright &y& Elsevier]

Purpose: In our previous study, we have found that the hypoxia-inducible factor 1α (HIF-1α) is upregulated in renal cell carcinoma (RCC) tissues compared with para-cancer normal tissues by 2-dimensional polyacrylamide gel electrophoresis. It was reported that hypoxic conditions were correlated with cancer stem cell generation and HIF-1α acted as a transcription regulator in nuclear HIF-1α expression. Therefore, in this study we investigate the relation between CD133 and nuclear HIF-1α expression levels in RCC tissues. Methods: In this study 61 RCC tissues from the patients that treated with radical nephrectomy were collected. Then, we investigated the expression of CD133 and nuclear HIF-1α expression by immunohistochemistry. To verify the relation between CD133 and nuclear HIF-1α expression, we treated 786-O cells with cobalt chloride. The expression of CD133 on 786-O cells was analyzed by flowcytometry. Results: The immunohistochemical study showed that CD133 was correlated with tumor stage and metastatic stage, whereas nuclear HIF-1α had no association with clinicopathological parameters. However, the expression of nuclear HIF-1α was correlated with CD133. The CD133 expression in 786-O cells was enhanced by cobalt chloride, which meant that CD133 expression was affected by hypoxia. Conclusions: Our study showed that in RCC, CD133 expression was strongly related to nuclear HIF-1α and the expression of CD133 might be upregulated under hypoxia environment. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) are considered useful prognostic factors for various cancers, and in 2014, our research group conducted a comparative experiment of CTC detection in patients with renal cell cancer (RCC). However, the reason for the low detection rate of CTCs in cancer patients using the CellSearch ® system is still unknown, although it has been hypothesized to be attributed to the likelihood that CTCs undergoing epithelial-mesenchymal transition (EMT) do not express the CTC biomarkers cytokeratin (CK)8/18/19 or epithelial cell adhesion molecule (EpCAM). The overall aim of the current study was to investigate the expression levels of CK8/18/19 and EpCAM in relation to the EMT biomarkers vimentin and E-cadherin in patients with RCC., Methods: Patients with RCC who had undergone radical nephrectomy or partial resection between May 2014 and December 2014 were initially recruited., Results: Among 34 RCC patients, nine co-expressed EpCAM and CK8/18/19 in primary tumor tissues. The CellSearch ® results showed that CK8/18/19 was expressed in 5 of 6 patients (5/6) and EpCAM was expressed in 6 patients (6/6). However, the isolation by size of tumor cells (ISET) technique showed these were co-expressed in only four of the 10. The expression of CK8/18/19, EpCAM, vimentin, and E-cadherin was distributed unequally in different enumeration groups of CTCs (all P>0.05), and the positive expression of CK8/18/19 was correlated with neutrophil number and tumor size (P<0.05). The positive expression of vimentin was correlated with the Karnofsky Performance Status (KPS) score and clinical stage of renal cancer patients (P<0.05)., Conclusions: Our results indirectly proved the occurrence of EMT in the formation of CTCs by comparing and analyzing the expression of CK8/18/19 and EpCAM in renal cancer tissues and the detection results of CTCs., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-22-142/coif). The authors have no conflicts of interest to declare., (2022 Translational Andrology and Urology. All rights reserved.)

Immune checkpoint inhibitors (ICIs) are a novel class of immunotherapy drugs that have improved the treatment of a broad spectrum of cancers as metastatic melanoma, non-small lung cancer or renal cell carcinoma. These humanized monoclonal antibodies target inhibitory receptors (e.g. CTLA-4, PD-1, LAG-3, TIM-3) and ligands (PD-L1) expressed on T lymphocytes, antigen presenting cells and tumor cells and elicit an anti-tumor response by stimulating immune system. Nevertheless, the improved overall survival is complicated by the manifestation of Immune-related Adverse Effects (irAEs). During treatment with ICIs, the most common adverse kidney effect is represented by the development of acute kidney injury (AKI) with the acute tubulointerstitial nephritis as recurrent histological feature. The mechanisms involved in ICIs-induced AKI include the re-activation of effector T cells previously stimulated by nephrotoxic drugs (i.e. by antibiotics), the loss of tolerance versus self-renal antigens, the increased PD-L1 expression by tubular cells or the establishment of a pro-inflammatory milieu with the release of self-reactive antibodies. For renal transplant recipient treated with ICIs, the increased incidence of rejection is a serious concern. Therefore, the combination of ICIs with mTOR inhibitors represents an emerging strategy. Finally, it is relevant to anticipate which patients under ICIs would experience severe irAEs and from a kidney perspective, to predict patients with higher risk of AKI. Here, we provide a detailed overview of ICIs-related nephrotoxicity and the recently described multicenter studies. Several factors have been reported as biomarkers of ICIs-irAEs, in this review we speculate on potential biomarkers for ICIs-associated AKI., (Copyright © 2020 Franzin, Netti, Spadaccino, Porta, Gesualdo, Stallone, Castellano and Ranieri.)

Objective: To evaluate Ang-2 expression alone and in combination with expression of cell proliferation and cell survival markers (MIB-1 and Bcl-2) and angiogenesis markers (VEGFR3 and CD31), and the associations of these markers with renal cell cancer (RCC) in long-term survival., Patients and Methods: Our study included 224 patients with RCC who were treated before the availability of antiangiogenic agents between 1985 and 1995, at the Pirkanmaa Hospital District in Finland. All tumor samples were reclassified and reevaluated by an experienced uropathologist, and parallel tissue microarrays (TMA) were performed for immunohistochemical analysis. Kaplan-Meier's survival estimation method and Cox proportional hazards models were used for survival analysis., Results: The percentage of Ang-2 expression in the tumor area varied from 0.07 to 25.65. Ang-2 expression was significantly associated with the tumor grade and stage, as well as the MIB-1, Bcl-2, and VEGFR3 expression (P = .042, P = .019, P = .039, P = .013, and P = .005, respectively). The highest Ang-2 expression predicted better survival, P < .05. High Bcl-2 and low MIB-1 expression combined with Ang-2 expression was associated with better survival. Multivariate analysis showed poorer survival in patients with low Ang-2 or high MIB-1 expressions: HR 1.89, 95% CI 1.16 to 3.08, P = .010 and HR 2.20, 95% CI 1.36 to 3.54, P = .001, respectively., Conclusions: Very high Ang-2 expression was associated with better survival in patients with RCC. Ang-2 expression correlated with tumor stage and grade, but it was still an independent prognostic factor in a multivariate analysis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

C12orf59 is newly identified gene in kidney. However, the relation of C12orf59 expression and clinic features is unknown. Here, our study showed that C12orf59 was broadly expressed in normal human tissues with high expression levels in kidney while its expression is beyond detectable in a panel of cancer cell lines. C12orf59 expression in RCC was significantly decreased compared with corresponding adjacent noncancerous tissues (P < 0.01). The decreased C12orf59 expression was correlated with lymph node status (P < 0.05), distant metastases (P < 0.05), poor survival (P < 0.001) (HR 3.00; 95% CI, 1.29-7.53), VHL non-sense mutations or frame-shift mutations (P < 0.01), and UMPP gene non-sense mutations or frame-shift mutations (P = 0.01). Thus, we propose that the decreased C12orf59 expression status is a prognostic biomarker of ccRCC and cooperates with the loss of VHL all the while promoting renal carcinogenesis.

Aim: To evaluate the expression levels of vascular endothelial growth factor receptor-3 (VEGFR3) and CD31 and assess their associations with grade, stage and survival in patients with renal cell cancer (RCC)., Patients and Methods: Our study included 224 consecutive patients who received treatment during the years 1985-1995 in Tampere Finland but had not been treated with modern anti-angiogenesis drugs. All tumor samples were re-classified and investigated using immunohistological techniques. Data were collected from patient records and the Finnish Cancer Registry., Results: In total, 54.2% and 98.2% of the tumor samples tested positive for VEGFR3 and CD31 expression, respectively. CD31 expression levels were classified into two groups according to the median level revealing that its high expression was nearly significantly associated with low tumor stage (p=0.069). In an age- and gender-adjusted analysis, low expression of CD31 associated with poorer survival. Grade 3 and grade 4 tumors had significantly higher mortality rates compared to those of grades 1-2 (hazard ratio (HR)=4.91; 95% confidence interval (CI)=1.12-20.4; p=0.029 for grade 3 and HR=9.31; 95% CI=2.23-38.8; p=0.002 for grade 4). In addition, stage 2, 3 and 4 tumors revealed that they possessed significantly higher mortality hazard ratios compared to those of stage 1 tumors (HR=2.62; 95% CI=1.27-5.41; p=0.009 for stage 2, HR=4.37;95% CI=2.29-8.3; p<0.001 for stage 3 and HR 13.8; 95% CI=7.18-26.7; p<0.001 for stage 4)., Conclusion: High CD31 expression associated significantly with better survival and VEGFR3 had no association with survival. Both higher tumor grade and stage were associated with a decreased survival time., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Claudins are tight junction proteins and their expression is often different in normal and corresponding tumor cells. In the present study, we determined how the expression of claudins 1-5 and 7 correlated to survival, grade and stage of patients with renal cell cancer (RCC)., Patients and Methods: Primary tumor samples were collected retrospectively from 229 RCC patients. Claudins were detected by immunohistochemistry using commercial monoclonal antibodies against claudins 1-5 and 7. Median survival time was 6.5 years confidence interval (CI) (4.5-8.5, n=224). Kaplan-Meier survival estimated method was used in survival analyses., Results: Positive expression was detected in 62%, 67%, 45%, 55%, 7% and 35% of cases for claudins 1, 2, 3, 4, 5 and 7, respectively. High expression of claudin 2 was observed in 20% of cases while high expression of other claudins was less frequent. Claudins were compared to classical prognostic factors. On cross-tabulation, claudin 1 (p<0.001) and claudin 2 (p=0.009) were significantly associated with lower-grade and higher-grade tumors, respectively. None of the claudins was significantly associated with tumor stage or patient survival., Conclusion: Claudins 1 and 2 were associated with tumor grade. However, none of the claudins was a more powerful prognostic factor than tumor stage., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)