Kidney Cancer
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Renal cell cancer (kidney cancer) is a disease in which malignant cells arise from tissues of the kidney. This is one of the less common types of cancer and it occurs more frequently in men compared to women. The vast majority of renal cell cancers are histologically classed as adenocarcinomas, these may be subdivided into clear cell and granular cell types (in some cases the 2 types can occur together in the same tumour). There are other less common types of non-adenocarcinoma kidney cancers including transitional cell carcinoma of the renal pelvis. Wilms' tumour is another type of kidney cancer, which is almost exclusively found in children.

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Latest Research Publications

Information Patients and the Public (4 links)


Information for Health Professionals / Researchers (4 links)

Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

Khan KH, Fenton A, Murtagh E, et al.
Reversible posterior leukoencephalopathy syndrome following sunitinib therapy: a case report and review of the literature.
Tumori. 2012 Sep-Oct; 98(5):139e-142e [PubMed]
Sunitinib is one of the standard targeted therapies used in metastatic renal cell carcinoma. It is generally a reasonably tolerated oral systemic therapy but can be occasionally associated with life-threatening toxicities. We present a case of reversible posterior encephalopathy, which is a rare but recognised side effect of the treatment.
Drug Development Unit, Royal Marsden Hospital, Sutton, London


Brown KW, Charles A, Dallosso A, et al.
Characterization of 17.94, a novel anaplastic Wilms' tumor cell line.
Cancer Genet. 2012; 205(6):319-26 [PubMed]
Despite considerable advances in understanding the molecular pathogenesis of Wilms' tumor (WT), its cell biology is less well understood, partly due to the paucity of established WT cell lines. We report here the establishment of a new anaplastic WT cell line, 17.94, which expressed NCAM, SALL1, and CITED1-phenotypic features expected of metanephric blastema-derived cells. Treatment of 17.94 cells with 12-O-Tetradecanoylphorbol 13-acetate caused morphological changes, which led to reduced NCAM and SALL1 expression, but expression of vimentin was maintained, indicating a potential for stromal differentiation. The 17.94 cell line contained a TP53 mutation, consistent with the anaplastic histology of the original tumor, but lacked mutations in WT1, WTX, or CTNNB1, which are the other genes involved in WT pathogenesis. The 17.94 cells showed no loss of heterozygosity at 7p, 11p, or 16q; however, DNA hypermethylation was detected at several loci, including the H19 differentially methylated region (indicative of loss of imprinting of IGF2 at 11p15) and at the PCDH@ gene clusters at 5q31. The derivation of the 17.94 cell line should help to further dissect the genetic-epigenetic interactions involved in the pathogenesis of WT.
University of Bristol, School of Cellular & Molecular Medicine
Research funded by:


Leung C, Trainer V, Short E, Venkatanarasimha N
A case of ossifying papillary renal cell carcinoma.
Urology. 2012; 80(1):e11-2 [PubMed]
Osseous metaplasia can occur in renal cell carcinomas. We report a case of a 52-year-old lady who presented with hematuria. Ossification associated with a renal cell carcinoma was demonstrated on computed tomography urography and confirmed by histopathologic examination.
Department of Radiology, University Hospital of Wales, Cardiff


Bielen A, Box G, Perryman L, et al.
Dependence of Wilms tumor cells on signaling through insulin-like growth factor 1 in an orthotopic xenograft model targetable by specific receptor inhibition.
Proc Natl Acad Sci U S A. 2012; 109(20):E1267-76 [PubMed] Free Access to Full Article
We have previously demonstrated an increased DNA copy number and expression of IGF1R to be associated with poor outcome in Wilms tumors. We have now tested whether inhibiting this receptor may be a useful therapeutic strategy by using a panel of Wilms tumor cell lines. Both genetic and pharmacological targeting resulted in inhibition of downstream signaling through PI3 and MAP kinases, G(1) cell cycle arrest, and cell death, with drug efficacy dependent on the levels of phosphorylated IGF1R. These effects were further associated with specific gene expression signatures reflecting pathway inhibition, and conferred synergistic chemosensitisation to doxorubicin and topotecan. In the in vivo setting, s.c. xenografts of WiT49 cells resembled malignant rhabdoid tumors rather than Wilms tumors. Treatment with an IGF1R inhibitor (NVP-AEW541) showed no discernable antitumor activity and no downstream pathway inactivation. By contrast, Wilms tumor cells established orthotopically within the kidney were histologically accurate and exhibited significantly elevated insulin-like growth factor-mediated signaling, and growth was significantly reduced on treatment with NVP-AEW541 in parallel with signaling pathway ablation. As a result of the paracrine effects of enhanced IGF2 expression in Wilms tumor, this disease may be acutely dependent on signaling through the IGF1 receptor, and thus treatment strategies aimed at its inhibition may be useful in the clinic. Such efficacy may be missed if only standard ectopic models are considered as a result of an imperfect recapitulation of the specific tumor microenvironment.
Department of Pediatric Oncology, Institute of Cancer Research, Sutton SM2 5NG
Research funded by:


Raza SA, Sohaib SA, Sahdev A, et al.
Centrally infiltrating renal masses on CT: differentiating intrarenal transitional cell carcinoma from centrally located renal cell carcinoma.
AJR Am J Roentgenol. 2012; 198(4):846-53 [PubMed]
OBJECTIVE: The objective of our study was to retrospectively determine the accuracy of CT for differentiating intrarenal transitional cell carcinoma (TCC) from centrally located renal cell carcinoma (RCC) and to define the most discriminating diagnostic CT features.
MATERIALS AND METHODS: CT studies of 98 pathologically proven central renal tumors (64 centrally located RCCs and 34 intrarenal TCCs) seen over 5 years at three university hospitals were reviewed by five specialty-trained radiologists who were blinded to the final diagnosis. Multiple CT features and global impression were graded on a 4-point score. The sensitivity and specificity of each feature and of global assessment were calculated and compared using receiver operating characteristic (ROC) analysis. Interobserver agreement (kappa values) was also calculated for each parameter.
RESULTS: All five readers recognized intrarenal TCCs with a high diagnostic accuracy (sensitivity, 90%; specificity, 90%; area under ROC curve [AUC], 0.80-0.95 for global assessment) with moderate-to-excellent interobserver agreement (κ = 0.72-1). Six CT features were most diagnostically specific for identifying intrarenal TCCs: tumor centered within the collecting system; focal filling defect in the pelvicalyceal system; preserved renal shape; absence of cystic or necrotic change; homogeneous tumor enhancement; and tumor extension toward the ureteropelvic junction (sensitivity, 68-82%; specificity, 79-89%; AUC, 0.75-0.84). There was moderate-to-good agreement among the readers over all these features (κ = 0.44-0.69).
CONCLUSION: Intrarenal TCC can be recognized with a high accuracy on CT; global impression showed the best diagnostic performance. A solid, homogeneously enhancing mass that is centered on the collecting system and extends toward the ureteropelvic junction combined with a focal pelvicalyceal filling defect and preserved renal outline is more likely to be an intrarenal TCC than a centrally located RCC.
Department of Clinical Radiology, St. George's Hospital, London


Gerlinger M, Rowan AJ, Horswell S, et al.
Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
N Engl J Med. 2012; 366(10):883-92 [PubMed]
BACKGROUND: Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.
METHODS: To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression.
RESULTS: Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors.
CONCLUSIONS: Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.).
Cancer Research UK London Research Institute, London
Research funded by:


O'Mahony FC, Faratian D, Varley J, et al.
The use of automated quantitative analysis to evaluate epithelial-to-mesenchymal transition associated proteins in clear cell renal cell carcinoma.
PLoS One. 2012; 7(2):e31557 [PubMed] Free Access to Full Article
BACKGROUND: Epithelial-to-mesenchymal transition (EMT) has recently been implicated in the initiation and progression of renal cell carcinoma (RCC). Some mRNA gene expression studies have suggested a link between the EMT phenotype and poorer clinical outcome from RCC. This study evaluated expression of EMT-associated proteins in RCC using in situ automated quantitative analysis immunofluorescence (AQUA) and compared expression levels with clinical outcome.
METHODS/PRINCIPAL FINDINGS: Unsupervised hierarchical cluster analysis of pre-existing RCC gene expression array data (GSE16449) from 36 patients revealed the presence of an EMT transcriptional signature in RCC [E-cadherin high/SLUG low/SNAIL low]. As automated immunofluorescence technology is dependent on accurate definition of the tumour cells in which measurements take place is critical, extensive optimisation was carried out resulting in a novel pan-cadherin based tumour mask that distinguishes renal cancer cells from stromal components. 61 patients with ccRCC and clinical follow-up were subsequently assessed for expression of EMT-associated proteins (WT1, SNAIL, SLUG, E-cadherin and phospho-β-catenin) on tissue microarrays. Using Kaplan-Meier analysis both SLUG (p = 0.029) and SNAIL (p = 0.024) (log rank Mantel-Cox) were significantly associated with prolonged progression free survival (PFS). Using Cox regression univariate and multivariate analysis none of the biomarkers were significantly correlated with outcome. 14 of the 61 patients expressed the gene expression analysis predicted EMT-protein signature [E-cadherin high/SLUG low/SNAIL low], which was not found to be associated to PFS when measured at the protein level. A combination of high expression of SNAIL and low stage was able to stratify patients with greater significance (p = 0.001) then either variable alone (high SNAIL p = 0.024, low stage p = 0.029).
CONCLUSIONS: AQUA has been shown to have the potential to identify EMT related protein targets in RCC allowing for stratification of patients into high and low risk groups, as well the ability to assess the association of reputed EMT signatures to progression of the disease.
Edinburgh Urological Cancer Group, Division of Pathology, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh
Research funded by:


Raj V, Alpendurada F, Christmas T, et al.
Cardiovascular magnetic resonance imaging in assessment of intracaval and intracardiac extension of renal cell carcinoma.
J Thorac Cardiovasc Surg. 2012; 144(4):845-51 [PubMed]
OBJECTIVES: About 1 in 5 patients with renal cell carcinoma have intravascular tumoral extension at presentation. Level of tumoral extension within inferior vena cava determines surgical approach, with higher extension requiring cardiopulmonary bypass. Tumoral invasion of inferior vena caval wall is associated with poor prognosis. We evaluated accuracy of magnetic resonance imaging (MRI) in assessing level of intravascular extension of renal cell carcinoma and predicting vessel wall invasion.
METHODS: MRIs and surgical database were reviewed from January 1999 to December 2008. Sixty-four patients with suspected intravascular extension of renal cell carcinoma underwent MRI. Forty-one underwent curative or palliative surgery at our institution and were included in final analysis. MRI scans were reviewed to determine intravascular extension and tumoral adherence to the vessel wall, as assessed by circumferential flow around the intravascular tumor and its mobility during different phases of cardiac cycle. MRI findings were correlated with surgical findings to assess accuracy.
RESULTS: There was 87.8% agreement (P < .001; κ = 0.82) between MRI and surgical findings regarding level of intravascular extension of tumor. MRI was highly sensitive and specific (93%) in assessing supradiaphragmatic extension (negative predictive value, 96%). Depending on sign used, sensitivities and negative predictive values in assessing tumoral adherence to vessel wall ranged from 86% to 95% and 81% to 91%, respectively.
CONCLUSIONS: MRI is highly accurate in staging intravascular and intracardiac extension, aiding in accurate preoperative surgical planning. MRI may help determine prognosis of renal cell carcinoma by accurately assessing tumoral adherence to the vessel wall.
Department of Radiology, Glenfield Hospital, University Hospitals of Leicester NHS Trust, Leicester


Nieto M, Borregaard J, Ersbøll J, et al.
The European Medicines Agency review of pazopanib for the treatment of advanced renal cell carcinoma: summary of the scientific assessment of the Committee for Medicinal Products for Human Use.
Clin Cancer Res. 2011; 17(21):6608-14 [PubMed]
On June 14, 2010, the European Commission issued a conditional marketing authorization valid throughout the European Union for pazopanib for the treatment of advanced renal cell carcinoma. Pazopanib is an antineoplastic agent that inhibits multiple receptor tyrosine kinases. The recommended oral dose is 800 mg once daily. The benefit of pazopanib is an increased progression-free survival. In the pivotal trial VEG105192, the median progression-free survival was 9.2 months (95% confidence interval, 7.4-12.9) in the pazopanib arm compared with 4.2 months (95% confidence interval, 2.8-4.2) in the placebo arm. The most common side effects include diarrhea, hair color change, hypertension, nausea, fatigue, anorexia, vomiting, dysgeusia, elevated alanine aminotransferase, elevated aspartate aminotransferase, and abdominal pain. The objective of this article is to summarize the scientific review of the application that led to approval in the European Union.
European Medicines Agency, London


Patel U, Ramachandran N, Halls J, et al.
Synchronous renal masses in patients with a nonrenal malignancy: incidence of metastasis to the kidney versus primary renal neoplasia and differentiating features on CT.
AJR Am J Roentgenol. 2011; 197(4):W680-6 [PubMed]
OBJECTIVE: The purpose of this study was to establish the contemporaneous frequency of metastases within the kidney as opposed to primary renal tumors in patients with an active primary nonrenal malignancy and to identify the differentiating features.
MATERIALS AND METHODS: We retrospectively identified all patients with an active primary nonrenal malignancy (group 1) who had also undergone at least 2 contrast-enhanced abdominal CT examinations spaced 1 year apart. The radiologic and pathologic data of these cases were reviewed and the incidence of metastasis to the kidney versus primary renal tumors established. These data were compared with a separate group who presented with primary renal malignancy from the outset (group 2).
RESULTS: In the study were 2340 patients with primary nonrenal malignancy (group 1) and 231 patients with a primary renal malignancy (group 2). For group 1, the mean age was 63 years and 51% were men; for group 2, the mean age was 59 years, and 58% were men. The differences were not statistically significant. Thirty-six patients in group 1 had a malignant renal mass; 21 were a result of kidney metastasis and the remaining 15 were a synchronous primary renal tumor (0.9% vs 0.6%). The kidney was the eighth most common site of metastatic spread. Metastases to the kidney were statistically more likely with higher tumor stage of the primary nonrenal malignancy (68% vs 46%, p = 0.0006) and in those with other sites of metastasis (p = 0.012, positive likelihood ratio [LR+] = 6.75). Compared with primary renal tumors, metastases to the kidney were more often solid (86% vs 53%, p = 0.019, LR+ = 3.7) and endophytic (76% vs 33%, p = 0.017, LR+ = 2.29). There were too few cases with calcification and bilateral tumors to reach a statistically significant conclusion. Tumor size, polar predominance, and enhancement pattern were similar in the two groups. The primary renal tumors seen in group 1 versus group 2 were similar regarding age and sex distribution, cell type, median size, and tumor stage.
CONCLUSION: Metastases to the kidney are uncommon in modern radiologic practice (0.9%, 21/2340 in this study), and a renal mass seen in a patient with nonrenal malignancy is nearly as likely to be an incidental primary renal tumor. Metastasis is more likely in those with higher tumor stage or if other viscera are also affected and is usually an asymptomatic, small, endophytic, and solid mass. If a renal mass seen in a patient with primary nonrenal malignancy proves to be a synchronous primary renal tumor, its cell type and stage will be similar to sporadic primary renal tumors.
Department of Radiology, St. George's Hospital and Medical School, Blackshaw Rd, London SW17 0QT


McGregor S
Surviving cancer without compromising aspirations.
Eur J Oncol Nurs. 2011; 15(3):201-3 [PubMed]
This short paper is a reflection of how one person coped, survived and grew following numerous metastatic incidences over a 20 year period. Surviving cancer is a complex process but coping with the threat of regular recurrence has required a coping strategy that embraced the disease, set it aside and refused to compromise hopes, dreams and future life. Central to this personal journey has been the need to redefine normality, live with and set aside the fear of future metastases and death and find an answer and meaning in a changing biology, increased morbidity and possible mortality. This paper contends that not compromising the direction of travel and being able to focus on a career has ensured that survival was valuable and valued. A working environment in which students' problems have been immediate has produced different stressors. These have ultimately forced personal worries to be set aside, while living with cancer has become normal and accepted.
University of Glasgow


Rudman SM, Jameson MB, McKeage MJ, et al.
A phase 1 study of AS1409, a novel antibody-cytokine fusion protein, in patients with malignant melanoma or renal cell carcinoma.
Clin Cancer Res. 2011; 17(7):1998-2005 [PubMed] Free Access to Full Article
PURPOSE: AS1409 is a fusion protein comprising a humanized antibody BC1 linked to interleukin-12 (IL-12). It is designed to deliver IL-12 to tumor-associated vasculature using an antibody targeting the ED-B variant of fibronectin.
EXPERIMENTAL DESIGN: We conducted a phase 1 trial of weekly infusional AS1409 in renal carcinoma and malignant melanoma patients. Safety, efficacy, markers of IL-12-mediated immune response, and pharmacokinetics were evaluated.
RESULTS: A total of 11 melanoma and 2 renal cell carcinoma patients were treated. Doses of 15 and 25 μg/kg were studied. Most drug-related adverse events were grade 2 or less, and included pyrexia, fatigue, chills, headache, vomiting, and transient liver function abnormalities. Three dose limiting toxicities of grade 3 fatigue and transaminase elevation were seen at 25 μg/kg. IFN-γ and interferon-inducible protein-10 (IP-10) were elevated in all patients, indicating activation of cell-mediated immune response; this was attenuated at subsequent cycles. Antidrug antibody responses were seen in all patients, although bioassays indicate these do not neutralize AS1409 activity. Plasma half-life was 22 hours and not dose-dependent. Five patients received 6 cycles or more and a best response of at least stable disease was seen in 6 (46%) patients. Partial response was seen in a melanoma patient, and disease shrinkage associated with metabolic response was maintained beyond 12 months in another melanoma patient despite previous rapid progression.
CONCLUSIONS: The maximum tolerated dose was established at 15 μg/kg weekly. AS1409 is well tolerated at this dose. Evidence of efficacy assessed by RECIST, functional imaging, and biomarker response warrants the planned further investigation using this dose and schedule in malignant melanoma.
King's College London, London
Research funded by:


Sonoda LI, Halim MY, Balan KK
Solitary phalangeal metastasis of renal cell carcinoma on bone scintigram.
Clin Nucl Med. 2011; 36(3):237-9 [PubMed]
Renal cell carcinoma is known to cause lytic metastasis at various sites including axial and appendicular skeleton. However, it is unusual to find an isolated metastasis of renal cell carcinoma in the distal extremity on bone scintigraphy. A 70-year-old woman with renal cell carcinoma was referred to the Nuclear Medicine Department for a bone scintigram to exclude metastasis. The whole-body planar images were unremarkable, but the local views of the hands demonstrated a solitary metastasis in the middle phalanx of the finger. This rare experience illustrates the need for including local views of extremities in a standard whole-body study.
Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge, England


Lu X, Wei W, Fenton J, et al.
Therapeutic targeting the loss of the birt-hogg-dube suppressor gene.
Mol Cancer Ther. 2011; 10(1):80-9 [PubMed]
Brit-Hogg-Dubé (BHD) syndrome, an autosomal dominant familial cancer, is associated with increased risk of kidney cancer. BHD syndrome is caused by loss-of-function mutations in the folliculin (FLCN) protein. To develop therapeutic approaches for renal cell carcinoma (RCC) in BHD syndrome, we adopted a strategy to identify tumor-selective growth inhibition in a RCC cell line with FLCN inactivation. The COMPARE algorithm was used to identify candidate anticancer drugs tested against the NCI-60 cell lines that showed preferential toxicity to low FLCN expressing cell lines. Fifteen compounds were selected and detailed growth inhibition (SRB) assays were done in paired BHD RCC cell lines (UOK257 derived from a patient with BHD). Selective sensitivity of FLCN-null over FLCN-wt UOK257 cells was observed in seven compounds. The most selective growth-inhibitory sensitivity was induced by mithramycin, which showed an approximately 10-fold difference in GI(50) values between FLCN-null (64.2 ± 7.9 nmol/L, n = 3) and FLCN-wt UOK257 cells (634.3 ± 147.9 nmol/L, n = 4). Differential ability to induce caspase 3/7 activity by mithramycin was also detected in a dose-dependent manner. Clonogenic survival studies showed mithramycin to be approximately 10-fold more cytotoxic to FLCN-null than FLCN-wt UOK257 cells (200 nmol/L). Following mithramycin exposure, UOK257-FLCN-null cells were mainly arrested and blocked in S and G(2)-M phases of the cell cycle and low dose of rapamycin (1 nmol/L) potentiated mithramycin sensitivity (1.5-fold in G(2)-M population and 2-fold in G(2)-M period time, 2xGI(50), 48 hours). These results provide a basis for further evaluation of mithramycin as a potential therapeutic drug for RCC associated with BHD.
Department of Medical and Molecular Genetics, School of Clinical and Experimental Medicine, University of Birmingham; Edgbaston, Birmingham B15 2TT, The United Kingdom.


Venugopal S, Hamid B, Doyle G, Pettersson BA
Renal angiomyoadenomatoid tumor.
Urology. 2011; 78(2):327-8 [PubMed]
Renal angiomyoadenomatoid tumor is a distinct pathologic entity that can mimic clear cell renal adenocarcinoma in presentation. The nature and behavior of these tumors are not well understood, and they require long-term follow-up to clarify their neoplastic potential.
Department of Urology, Countess of Chester Foundation NHS Foundation Trust, Cheshire


Hamdoon Z, Jerjes W, Upile T, et al.
Metastatic renal cell carcinoma to the orofacial region: A novel method to alleviate symptoms and control disease progression.
Photodiagnosis Photodyn Ther. 2010; 7(4):246-50 [PubMed]
Head and neck metastatic tumours are uncommon. The primary tumors most likely to metastasize are those of the thyroid, breast, and lungs. The management of metastatic carcinoma in the orofacial region is variable. Palliative and symptomatic approaches are the mainstay in the management. The purpose of this case report is to highlight the feasibility of using PDT to alleviate nasal and visual symptoms and control the growth of metastatic renal cell carcinoma to the orofacial region.
UCLH Head and Neck Centre, London


Begent J, Sebire NJ, Levitt G, et al.
Pilot study of F(18)-Fluorodeoxyglucose Positron Emission Tomography/computerised tomography in Wilms' tumour: correlation with conventional imaging, pathology and immunohistochemistry.
Eur J Cancer. 2011; 47(3):389-96 [PubMed]
Wilms' tumour is the second most common paediatric solid tumour. Prognosis is good although higher stage disease carries significant mortality and treatment related morbidity. In the UK, risk stratification is based on histological response to pre-operative chemotherapy. F(18)-Fluorodeoxyglucose Positron Emission Tomography (F(18)FDG-PET) is an emerging functional imaging technique in paediatric oncology. Little is known about the relationship between F(18)FDG-PET images and the disease process of Wilms' tumour. We performed F(18)FDG-PET/CT scans in seven children with Wilms' tumour after induction chemotherapy, immediately before surgery. The standard uptake values (SUV) of F(18)FDG-PET/CT images were related to conventional imaging and histopathological findings. In total seven children were studied. F(18)FDG-PET/CT was consistently safely performed. All tumours showed F(18)FDG activity. Four tumours had activity with SUV/bw max >5 g/ml. Histological examination of these active areas revealed viable anaplastic Wilms' tumour. Furthermore, in these four tumours GLUT-1 and Ki67 immunostaining was strongly positive. Three further tumours demonstrated lower uptake (SUV/bw max <5 g/ml), which represented areas of microscopic foci of residual viable tumour mixed with post chemotherapy change. Metastatic disease was F(18)FDG avid in two of four children with stage four diseases. In conclusion, following chemotherapy, active Wilms' tumour is F(18)FDG avid and higher SUV was seen in histologically high risk disease.
Department of Paediatrics and Adolescents, University College Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PQ


Powis M
Neonatal renal tumours.
Early Hum Dev. 2010; 86(10):607-12 [PubMed]
Neonatal renal tumours are rare, with only 7% of all neonatal tumours arising from the kidney. Presentation is usually as a flank mass or as a coincidental finding on either antenatal or postnatal ultrasound. Mesoblastic nephroma is the most common tumour to be found at this age, but Wilms' tumour and other malignant and benign tumours occur. Cross sectional imaging is useful to delineate the extent of the disease. Given the low malignant potential of these tumours, treatment is by radical nephroureterctomy, except in cases with bilateral disease or syndromic patients with a high incidence of metachronous tumours. Chemotherapy is rarely indicated. Survival is generally excellent for all tumour types in this age group, the exception being malignant rhabdoid tumour of the kidney which may have metastases at presentation.
Department of Paediatric Surgery, Leeds Teaching Hospitals NHS Trust, Leeds, LS1 3EX


Gore ME, Hariharan S, Porta C, et al.
Sunitinib in metastatic renal cell carcinoma patients with brain metastases.
Cancer. 2011; 117(3):501-9 [PubMed]
BACKGROUND: In a broad patient population with metastatic renal cell carcinoma (RCC), enrolled in an open-label, expanded access program (EAP), the safety profile of sunitinib was manageable, and efficacy results were encouraging. Here, the authors report results for patients with baseline brain metastases participating in this global EAP.
METHODS: Previously treated and treatment-naive metastatic RCC patients ≥18 years received sunitinib 50 mg orally, once daily, on Schedule 4/2. Safety was assessed regularly, tumor measurements done per local practice, and survival data collected where possible. Analyses were done in the modified intention-to-treat (ITT) population, consisting of all patients who received ≥1 dose of sunitinib.
RESULTS: As of December 2007, 4564 patients had enrolled in 52 countries. Of these enrollees, 4371 were included in the modified ITT population, of whom 321 (7%) had baseline brain metastases and had received a median of 3 treatment cycles (range 1-25). Reasons for their discontinuation included lack of efficacy (32%) and adverse events (8%). The most common grade 3-4 treatment-related adverse events were fatigue and asthenia (both 7%), thrombocytopenia (6%), and neutropenia (5%), the incidence of which were comparable to that for the overall EAP population. Of 213 evaluable patients, 26 (12%) had an objective response. Median progression-free survival and overall survival were 5.6 months (95% CI, 5.2-6.1) and 9.2 months (95% CI, 7.8-10.9), respectively.
CONCLUSIONS: In patients with brain metastases from RCC, the safety profile of sunitinib was comparable to that in the general metastatic RCC population, and sunitinib showed evidence of antitumor activity.
Royal Marsden Hospital NHS Trust, London


Bozas G, Roy A, Ramasamy V, Maraveyas A
Osteonecrosis of the jaw after a single bisphosphonate infusion in a patient with metastatic renal cancer treated with sunitinib.
Onkologie. 2010; 33(6):321-3 [PubMed]
BACKGROUND: Osteonecrosis of the jaw (ONJ) is recognised as an important adverse effect of intravenous bisphosphonates. Recent reports have suggested that antiangiogenic agents may promote the development of this condition.
CASE REPORT: We report a case of ONJ occurring within days after the first infusion of zoledronic acid in a patient being treated with sunitinib for metastatic renal cancer. No dental procedure contributed to the occurrence of ONJ. The patient had previously experienced oral mucositis caused by sunitinib. ONJ improved with conventional oral hygiene measures, zoledronic acid discontinuation, and hyperbaric oxygen treatment.
CONCLUSIONS: Sunitinib-induced mucosal injury and inhibition of angiogenic signalling pathways, also involved in bone repair and remodelling, may have precipitated the phenomenon. A possible synergistic effect may need to be increasingly addressed in the clinical setting since the concomitant use of sunitinib with bisphosphonates is becoming common.
Academic Department of Medical Oncology, Castle Hill Hospital, Cottingham, Hull and East Yorkshire Hospitals NHS Trust


Chetcuti K, Barnard J, Loggos S, et al.
Massive hemothorax secondary to metastatic renal carcinoma.
Ann Thorac Surg. 2010; 89(6):2014-6 [PubMed]
We present the case of a 78-year-old man with a past history of nephrectomy for renal cell carcinoma who was brought to the emergency room in hypovolemic shock after suddenly collapsing at home. A chest roentgenogram taken on admission showed a large pleural effusion on the right with a mediastinal shift to the left. A contrast computed tomographic scan of his chest excluded aortic dissection. An emergency right thoracotomy was performed, which revealed a chest wall tumor that was bleeding profusely. The tumor was biopsied after the bleeding was controlled. The histologic report revealed metastatic renal cell carcinoma, which is a rare cause for a spontaneous massive hemothorax.
Lancashire Cardiac Centre, Victoria Hospital, Whinney Heys Road, Blackpool, Lancashire


Timpson NJ, Brennan P, Gaborieau V, et al.
Can lactase persistence genotype be used to reassess the relationship between renal cell carcinoma and milk drinking? Potentials and problems in the application of Mendelian randomization.
Cancer Epidemiol Biomarkers Prev. 2010; 19(5):1341-8 [PubMed]
BACKGROUND: Increased risk of renal cell carcinoma (RCC) with milk consumption has been reported from observational studies. Whether this represents a causal association or is a result of confounding or bias is unclear. We assessed the potential for using genetic variation in lactase persistence as a tool for the study of this relationship.
METHODS: Using a large, hospital-based case-control study, we used observational, phenotypic, and genetic data to determine whether the MCM6 -13910 C/T(rs4988235) variant may be used as a nonconfounded and unbiased marker for milk consumption.
RESULTS: Consumption of milk during adulthood was associated with increased risk of RCC [odds ratio (OR), 1.35; 95% confidence interval (95% CI), 1.03-1.76; P=0.03]. Among controls, consumption of milk was associated with the lactase persistence genotype at rs4988235 (OR, 2.39; 95% CI, 1.81-3.15; P=6.9x10(-10)); however, the same genotype was not associated with RCC (OR, 1.01; 95% CI, 0.83-1.22; P=0.9). In controls, milk consumption was associated with confounding factors, including smoking and educational attainment, whereas genotypes at rs4988235 showed negligible association with confounding factors.
CONCLUSION: The absence of an association between the MCM6 genotype and RCC suggests that observational associations between milk consumption and RCC may be due to confounding or bias.
IMPACT: Although these data suggest that associations between milk consumption and RCC may be spurious, if the association between genotype and behavioral exposure is weak, then the power of this test may be low. The nature of intermediate risk factor instrumentation is an important consideration in the undertaking and interpretation of this type of causal analysis experiment.
MRC Centre for Causal Analysis in Translational Epidemiology, Department of Social Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN
Research funded by:


Crow P, Keeley FX
Prevention and handling of complications of renal focal therapies.
J Endourol. 2010; 24(5):765-7 [PubMed]
Small renal lesions often confer relatively low oncologic risk and, as such, dictate for treatment strategies with low morbidity. Minimally invasive ablative techniques have been developed and can deliver good outcomes where used judiciously. The potential risks of treatment relate to the method of ablation, the route by which it is delivered, together with patient and tumor factors. The complications associated with radiofrequency ablation and cryoablation, delivered via percutaneous and laparoscopic approaches, are considered in this review. Percutaneous ablation appears to be associated with lower rates of morbidity but higher rates of recurrence when compared with laparoscopic ablation. The ability to dissect the lesion away from surrounding structures is limited with the percutaneous approach, which can lead to poor outcomes when treating lesions close to the ureter or hilum. Hemorrhagic complications that are seen with laparoscopic cryoablation are most often associated with tumor fracture during the freeze-thaw cycle. This is encountered most frequently in larger, peripheral lesions but may be mitigated by slowing the freeze rate. Postablation inpatient stays are often short, and early signs of complication are often nonspecific. This combination can lead to significant delay in the recognition of postablative problems with a resultant increase in morbidity. A high index of suspicion together with appropriate use of imaging allows for earlier detection and management of complications.
Bristol Urological Institute, Southmead Hospital, Bristol


Williams RD, Al-Saadi R, Chagtai T, et al.
Subtype-specific FBXW7 mutation and MYCN copy number gain in Wilms' tumor.
Clin Cancer Res. 2010; 16(7):2036-45 [PubMed]
PURPOSE: Wilms' tumor (WT), the most common pediatric renal malignancy, is associated with mutations in several well-characterized genes, most notably WT1, CTNNB1, WTX, and TP53. However, the majority of cases do not harbor mutations in these genes. We hypothesized that additional drivers of tumor behavior would be contained within areas of consistent genomic copy number change, especially those associated with the WT risk groups defined by the International Society of Paediatric Oncology (SIOP).
EXPERIMENTAL DESIGN: We analyzed high-resolution (Affymetrix 250K single nucleotide polymorphism array) genomic copy number profiles of over 100 tumors from selected risk groups treated under the SIOP protocols, further characterizing genes of interest by sequencing, Multiplex Ligation-dependent Probe Amplification, or fluorescence in situ hybridization.
RESULTS: We identified FBXW7, an E3 ubiquitin ligase component, as a novel Wilms' tumor gene, mutated or deleted in approximately 4% of tumors examined. Strikingly, 3 of 14 (21%) of tumors with epithelial type histology after neoadjuvant chemotherapy had FBXW7 aberrations, whereas a fourth WT patient had germline mutations in both FBXW7 and WT1. We also showed that MYCN copy number gain, detected in 9 of 104 (8.7%) of cases, is relatively common in WT and significantly more so in tumors of the high risk diffuse anaplastic subtype (6 of 19, 32%).
CONCLUSIONS: Because MYCN is itself a target of FBXW7-mediated ubiquitination and degradation, these results suggest that a common pathway is dysregulated by different mechanisms in various WT subtypes. Emerging therapies that target MYCN, which is amplified in several other pediatric cancers, may therefore be of value in high risk Wilms' tumor.
Section of Paediatric Oncology, Institute of Cancer Research, Sutton, Surrey
Research funded by:


El-Hariry I, Powles T, Lau MR, et al.
Amplification of epidermal growth factor receptor gene in renal cell carcinoma.
Eur J Cancer. 2010; 46(5):859-62 [PubMed]
Expression of epidermal growth factor receptor (EGFR) may be of prognostic value in renal cell cancer (RCC). Gene amplification of EGFR was investigated in a cohort of 315 patients with advanced RCC from a previously reported randomised study. Using fluorescent in situ hybridisation, only 2 patients (0.6%) had gene amplification; therefore gene amplification is of no prognostic value in RCC.
Oncology Business Unit, GlaxoSmithKline, London UB11 1BT


Bhatia S, Ng S, Hodder SC
Metastatic cutaneous head and neck renal cell carcinoma with no known primary: case report.
Br J Oral Maxillofac Surg. 2010; 48(3):214-5 [PubMed]
Renal cell carcinoma represents 2-3% of all adult malignancies, and metastasis to the head and neck is a presenting complaint in 8% of these patients. Cutaneous facial renal cell carcinoma with no known primary renal tumour is unusual. We report a case of renal cell carcinoma of the nose with no known primary.
Morriston Hospital, ABM NHS Trust, Morriston Swansea


Pwint TP, Macaulay V, Roberts IS, et al.
An adult Xp11.2 translocation renal carcinoma showing response to treatment with sunitinib.
Urol Oncol. 2011 Nov-Dec; 29(6):821-4 [PubMed]
A rare variant of renal cell carcinoma (RCC) with a translocation involving Xp11.2 has become increasingly recognized as a separate entity in the 2004 World Health Organization (WHO) kidney carcinoma classification. These tumors predominantly affect children and young adults and tend to present with advanced stage disease. Although reported to be indolent in children, adult cases run a more aggressive course. Little is known about their natural history, prognosis and response to therapy. We report a case of Xp11 translocation renal cancer in a 33-year-old male patient who presented with widespread rapidly progressive metastatic disease involving extensive intra-thoracic lymph nodes, supra-clavicular, retroperitoneal lymph nodes, lung nodules, and peritoneal mass. He had failed to respond to treatment with high dose interleukin 2, but showed a significant clinical response to treatment with the multikinase inhibitor sunitinib. CT scan performed after 3 cycles (18 weeks) of therapy revealed more than 65% reduction of measurable disease by response evaluation criteria in solid tumors (RECIST) criteria, resolution of other assessable lesions, and a clinical benefit that lasted for over 13 months. But unfortunately, this was subsequently followed by a rapidly progressive course. The well-recognized clinical efficacy of multikinase inhibitors such as sunitinib and sorafenib is based on the outcomes in patients with clear cell histology. There is limited data on efficacy in non-clear cell RCC, but activity in translocation RCC has not been reported. To our knowledge, this is the first documented case of Xp11 translocation carcinoma to have demonstrated an objective durable response to sunitinib. It remains unclear how resistance to sunitinib develops, but the results to date support further evaluation of sunitinib in cases of translocation RCC.
Medical Oncology Unit, Churchill Hospital, Oxford


Noon AP, Smith DJ, McAndrew P
Magnetic resonance imaging characterization of a mucinous tubular and spindle cell carcinoma of the kidney detected incidentally during an ectopic pregnancy.
Urology. 2010; 75(2):247-8 [PubMed]
Mucinous tubular and spindle cell carcinoma is an extremely rare variant of renal cell carcinoma, with only 47 cases reported previously. To our knowledge, this is the first time that contrast-enhanced magnetic resonance imaging reconstructive appearances and characteristics of this tumor have been published. This tumor presented incidentally in a 35-year-old woman with an ectopic pregnancy.
Department of Urology, Royal Hallamshire Hospital, South Yorkshire


Dallosso AR, Hancock AL, Szemes M, et al.
Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms' tumor.
PLoS Genet. 2009; 5(11):e1000745 [PubMed] Free Access to Full Article
Wilms' tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to alpha-, beta-, and gamma-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms' tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA-induced reduction of PCDHG@ encoded proteins leads to elevated beta-catenin protein, increased beta-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses beta-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling.
Cancer and Leukaemia in Childhood-Sargent Research Unit, Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol


Miller RE, Larkin JM
Combination systemic therapy for advanced renal cell carcinoma.
Oncologist. 2009; 14(12):1218-24 [PubMed]
Outcomes for patients with advanced renal cell carcinoma (RCC) have improved significantly in recent years with the development of novel noncytotoxic systemic therapies. The multitargeted kinase inhibitors sunitinib and sorafenib have been approved for the treatment of advanced RCC, and bevacizumab, a monoclonal anti-vascular endothelial growth factor antibody, has shown significant clinical activity, both as a single agent and in combination with interferon-alpha. The mammalian target of rapamycin inhibitors temsirolimus and everolimus have led to longer overall survival times in poor-risk patients in the first-line setting and longer progression-free survival times in kinase inhibitor refractory patients in the second-line setting, respectively. Despite these advances, almost all patients develop resistance to treatment and cure is rarely seen. There is therefore a need to overcome resistance, induce longer lasting remissions, and improve survival. A potential approach to this is to combine active agents, and the clinical data for combination therapy with novel targeted agents in advanced RCC are reviewed here.
Department of Medicine, Royal Marsden Hospital, London, SW3 6JJ


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