Displaying publications 1 - 20 of 39 in total

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  1. Chan VW, Tan WS, Leow JJ, Tan WP, Ong WLK, Chiu PK, et al.
    World J Urol, 2021 Dec;39(12):4295-4303.
    PMID: 34031748 DOI: 10.1007/s00345-021-03734-1
    PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era.

    METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared.

    RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p 

    Matched MeSH terms: Kidney Neoplasms/pathology
  2. Erman M, Biswas B, Danchaivijitr P, Chen L, Wong YF, Hashem T, et al.
    BMC Cancer, 2021 Sep 14;21(1):1021.
    PMID: 34521387 DOI: 10.1186/s12885-021-08738-z
    BACKGROUND: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.

    METHODS: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months. Secondary endpoints were ORR, PFS, safety and tolerability, and relative dose intensity (RDI).

    RESULTS: Overall, 190 patients with a median age of 61 years (range: 22.0-96.0) were included. Most patients were Asian (70%), clear-cell type RCC was the most common (81%), with a favourable (9%), intermediate (47%), poor (10%), and unknown (34%) MSKCC risk score. At the end of the observational period, 78 patients completed the observational period and 112 discontinued the study; 60% of patients had the starting dose at 800 mg. Median RDI was 82%, with 52% of patients receiving  10%) TEAEs related to pazopanib included diarrhoea (30%), palmar-plantar erythrodysesthesia syndrome (15%), and hypertension (14%).

    CONCLUSIONS: Results of the PARACHUTE study support the use of pazopanib in patients with advanced or mRCC who are naive to VEGF-TKI therapy. The safety profile is consistent with that previously reported by pivotal and real-world evidence studies.

    Matched MeSH terms: Kidney Neoplasms/pathology
  3. Marafi F, Sasikumar A, Aldaas M, Esmail A
    Clin Nucl Med, 2021 Jan;46(1):e65-e67.
    PMID: 33181733 DOI: 10.1097/RLU.0000000000003354
    A 46-year-old man with end-stage renal disease and renal cell carcinoma underwent F-FDG PET/CT for initial staging followed by F-PSMA-1007 PET/CT. Unlike F-FDG, which undergoes renal clearance, F-PSMA-1007 undergoes hepatobiliary clearance and thus generates superior quality images. F-PSMA-1007 PET/CT showed intense tracer-avid left renal mass lesion (FDG nonavid); lytic bone lesions (FDG avid) and single liver lesion (FDG nonavid). This case highlights the superiority of F-PSMA-1007 over F-FDG PET/CT in identifying primary lesion as well as metastatic sites in case of renal cell carcinoma even in the presence of end-stage renal disease.
    Matched MeSH terms: Kidney Neoplasms/pathology*
  4. Morais C, Rajandram R, Blakeney JS, Iyer A, Suen JY, Johnson DW, et al.
    PLoS One, 2021;16(3):e0248983.
    PMID: 33765016 DOI: 10.1371/journal.pone.0248983
    Expression of the protease sensing receptor, protease activated receptor-2 (PAR2), is elevated in a variety of cancers and has been promoted as a potential therapeutic target. With the development of potent antagonists for this receptor, we hypothesised that they could be used to treat renal cell carcinoma (RCC). The expression of PAR2 was, therefore, examined in human RCC tissues and selected RCC cell lines. Histologically confirmed cases of RCC, together with paired non-involved kidney tissue, were used to produce a tissue microarray (TMA) and to extract total tissue RNA. Immunohistochemistry and qPCR were then used to assess PAR2 expression. In culture, RCC cell lines versus primary human kidney tubular epithelial cells (HTEC) were used to assess PAR2 expression by qPCR, immunocytochemistry and an intracellular calcium mobilization assay. The TMA revealed an 85% decrease in PAR2 expression in tumour tissue compared with normal kidney tissue. Likewise, qPCR showed a striking reduction in PAR2 mRNA in RCC compared with normal kidney. All RCC cell lines showed lower levels of PAR2 expression than HTEC. In conclusion, we found that PAR2 was reduced in RCC compared with normal kidney and is unlikely to be a target of interest in the treatment of this type of cancer.
    Matched MeSH terms: Kidney Neoplasms/pathology*
  5. Shi T, Huang Q, Liu K, Du S, Fan Y, Yang L, et al.
    Eur Urol, 2020 10;78(4):592-602.
    PMID: 32305170 DOI: 10.1016/j.eururo.2020.03.020
    BACKGROUND: Robot-assisted thrombectomy (RAT) for inferior vena cava (IVC) thrombus (RAT-IVCT) is being increasingly reported. However, the techniques and indications for robot-assisted cavectomy (RAC) for IVC thrombus are not well described.

    OBJECTIVE: To develop a decision-making program and analyze multi-institutional outcomes of RAC-IVCT versus RAT-IVCT.

    DESIGN, SETTING, AND PARTICIPANTS: Ninety patients with renal cell carcinoma (RCC) with level II IVCT were included from eight Chinese urological centers, and underwent RAC-IVCT (30 patients) or RAT-IVCT (60 patients) from June 2013 to January 2019.

    SURGICAL PROCEDURE: The surgical strategy was based on IVCT imaging characteristics. RAT-IVCT was performed with standardized cavotomy, thrombectomy, and IVC reconstruction. RAC-IVCT was mainly performed in patients with extensive IVC wall invasion when the collateral blood vessels were well-established. For right-sided RCC, the IVC from the infrarenal vein to the infrahepatic veins was stapled. For left-sided RCC, the IVC from the suprarenal vein to the infrahepatic veins was removed and caudal IVC reconstruction was performed to ensure the right renal vein returned through the IVC collaterals.

    MEASUREMENTS: Clinicopathological, operative, and survival outcomes were collected and analyzed.

    RESULTS AND LIMITATIONS: All procedures were successfully performed without open conversion. The median operation time (268 vs 190 min) and estimated blood loss (1500 vs 400 ml) were significantly greater for RAC-IVCT versus RAT-IVCT (both p < 0.001). IVC invasion was a risk factor for progression-free and overall survival at midterm follow-up. Large-volume and long-term follow-up studies are needed.

    CONCLUSIONS: RAC-IVCT or RAT-IVCT represents an alternative minimally invasive approach for selected RCC patients with level II IVCT. Selection of RAC-IVCT or RAT-IVCT is mainly based on preoperative IVCT imaging characteristics, including the presence of IVC wall invasion, the affected kidney, and establishment of the collateral circulation.

    PATIENT SUMMARY: In this study we found that robotic surgeries for level II inferior vena cava thrombus were feasible and safe. Preoperative imaging played an important role in establishing an appropriate surgical plan.

    Matched MeSH terms: Kidney Neoplasms/pathology*
  6. Tan HCL, Tan JH, Vellusamy VM, Vasavan Y, Lim CS
    Malays J Pathol, 2020 Aug;42(2):267-271.
    PMID: 32860380
    INTRODUCTION: Majority of Wilms tumour (WT) responds well to pre-operative chemotherapy. In Malaysia, incidence of WT is rare with only two cases reported per one million populations yearly. This case report is to highlight on the awareness of WT in an Asian population and highlight two cases and challenges faced after pre-operative chemotherapy.

    CASE REPORT: In this case series, we report on two cases of WT which had poor response to pre-operative chemotherapy. Both cases underwent surgery after pre-operative chemotherapy and recovery was uneventful during a two-year follow-up.

    DISCUSSION: Both patients had chemotherapy prior planned surgery, but had unfortunate poor tumour response. The tumour progressed in size which required a radical nephrectomy. The histology report for the first case had more than 60% blastemal cells remaining despite giving pre-operative chemotherapy with no focal anaplasia. This showed poor response to chemotherapy evidenced by the high number of blastemal cells. The second case was a stromal type WT which is known for poor response and may lead to enhancement of growth and maturation induced by chemotherapy. These were the possible reason of poor response of WT in these two cases.

    Matched MeSH terms: Kidney Neoplasms/pathology
  7. Chen EJ, Tan TH, Chew MT, Chye PC
    Clin Nucl Med, 2020 Jul;45(7):e317-e319.
    PMID: 32404702 DOI: 10.1097/RLU.0000000000003053
    Recent case reports and series have demonstrated the usefulness of Ga/F-PSMA PET/CT in restaging recurrent renal cancer after nephrectomy. We presented a case of a patient with renal mass who had undergone both F-FDG and Ga-PSMA PET/CT for diagnosis and staging. Concordant tracer uptake in the primary tumor and metastatic lesions was demonstrated by both radiotracers. Final histopathological reports revealed clear cell renal cell carcinoma. Furthermore, unusual left metacarpal bone metastasis was also detected.
    Matched MeSH terms: Kidney Neoplasms/pathology
  8. Perumal K, Mun KS, Yap NY, Razack AHA, Gobe GC, Ong TA, et al.
    Biomed Res Int, 2020;2020:3682086.
    PMID: 32802842 DOI: 10.1155/2020/3682086
    Background: The mechanisms that link obesity and cancer development are not well-defined. Investigation of leptin and leptin receptor expressions may help define some of the mechanisms. These proteins are known for associating with the immune response, angiogenesis and, signalling pathways such as JAK2/STAT3, PI3K, and AKT pathways. Tissue proteins can be easily detected with immunohistochemistry (IHC), a technique widely used both in diagnostic and research laboratories. The identification of altered levels of leptin and leptin receptor proteins in tumour tissues may lead to targeted treatment for cancer.

    Objective: The objective of this study was to use IHC to compare leptin and leptin receptor expressions in clear cell renal cell carcinomas (ccRCC) in non-obese and obese patients to determine the association between these proteins with the clinicopathological features and prognosis of ccRCC. Patients and Methods. The study involved 60 patients who underwent nephrectomy of which 34 were obese, as assessed using body mass index (BMI). Nephrectomy samples provided tissues of ccRCC and adjacent non-cancerous kidney. The intensity and localization of leptin and leptin receptor protein expressions were evaluated using IHC and correlated with clinicopathological features and clinical outcomes. Aperio ImageScope morphometry and digital pathology were applied to assess the IHC results. The chi-square test was used to determine if there was any significant association between the proteins and the clinicopathological features. The Kaplan-Meier test was used to determine the overall survival, disease-free survival, and recurrence-free survival. A value of p < 0.05 was considered significant.

    Results: There was neither significant difference in the overall cellular and nuclear expressions of leptin and leptin receptor between non-cancerous kidney and ccRCC tissues nor in non-obese and obese individuals with ccRCC.

    Conclusion: In this present study, it was revealed that leptin and leptin receptor were not associated with tumour characteristics and progression of ccRCC patients. Interestingly, nuclear expression of leptin was significantly associated with overall survival. However, the significance of these proteins as biomarkers in other RCC histotypes is still unclear.

    Matched MeSH terms: Kidney Neoplasms/pathology
  9. Samberkar S, Rajandram R, Mun KS, Samberkar P, Danaee M, Zulkafli IS
    Malays J Pathol, 2019 Dec;41(3):233-242.
    PMID: 31901907
    INTRODUCTION: Tissue biomarker carbonic anhydrase IX (CAIX) is purported to have prognostic value for renal cell carcinoma (RCC) but contradicting findings from previous studies have also been documented. This study aims to perform a systematic review and meta-analysis on the role of CAIX in RCC disease progression.

    MATERIALS AND METHODS: Following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines, online searches of multiple databases were performed to retrieve articles from their inception until December 2017. Inclusion criteria included all English-based original articles of immunohistochemistry (IHC) studies investigating CAIX expression in human RCC tissue. Four articles were finally selected for meta-analysis with a total of 1964 patients. Standard meta-analysis methods were applied to evaluate the role of CAIX in RCC prognosis. The relative risk (RR) and its 95% confidence interval (CI) were recorded for the association between biomarker and prognosis, and data were analysed using MedCalc statistical software.

    RESULTS: The meta-analysis showed that high CAIX expression was associated with low tumour stage (RR 0.90%, 95% CI 0.849-0.969, p= 0.004), low tumour grade (RR 0.835%, 95% CI 0.732-0.983, p= 0.028), absence of nodal involvement (RR 0.814%, 95% CI 0.712-0.931, p= 0.003) and better ECOS-PS index (RR 0.888%, 95% CI 0.818-0.969, p= 0.007). The high tissue CAIX expression in RCC is hence an indication of an early malignancy with a potential to predict favourable disease progression and outcome.

    CONCLUSION: The measurement of this marker may be beneficial to determine the course of the illness. It is hoped that CAIX can be developed as a specific tissue biomarker for RCC in the near future.

    Matched MeSH terms: Kidney Neoplasms/pathology*
  10. Yap NY, Yap FN, Perumal K, Rajandram R
    Biomarkers, 2019 Sep;24(6):607-614.
    PMID: 31215811 DOI: 10.1080/1354750X.2019.1634763
    Context: Metabolic imbalance in renal cell carcinoma (RCC) can lead to abnormal adiponectin levels. Objective: To evaluate circulating adiponectin as a detection or predictive marker for RCC. Methods: A comprehensive literature search and meta-analysis was performed on studies reporting circulating adiponectin levels and RCC. The meta-analysis was performed using RevMan. Results: Seven studies compared the circulating adiponection levels between RCC cases and controls. Adiponectin level was significantly lower in RCC cases compared to controls at pre-diagnosis and pre-operative time-points. RCC stage, grade and subtype did not affect adiponectin levels. Conclusion: Low circulating adiponectin could be a predictive or risk factor for RCC.
    Matched MeSH terms: Kidney Neoplasms/pathology
  11. Nyanti L, Samsudin A, Tiong IK
    J Med Case Rep, 2019 Jun 21;13(1):188.
    PMID: 31221202 DOI: 10.1186/s13256-019-2122-8
    BACKGROUND: Leser-Trélat syndrome, which manifests as eruptive multiple seborrheic keratoses, is a rare paraneoplastic sign. Hyponatremia in the elderly population is an often overlooked but potentially sinister biochemical abnormality. Cancer-related causes of hyponatremia include syndrome of inappropriate antidiuretic hormone secretion, cerebral or renal salt wasting, and adrenal dysfunction. We report a case of an elderly man who presented with both syndrome of inappropriate antidiuretic hormone secretion and Leser-Trélat syndrome, and was eventually found to have renal malignancy.

    CASE PRESENTATION: A 74-year-old indigenous Malaysian man with underlying chronic kidney disease presented with recurrent admissions for hyponatremia with parameters indicative of syndrome of inappropriate antidiuretic hormone secretion, constitutional symptoms, and diffuse skin lesions suggestive of multiple seborrheic keratoses. A radiological workup revealed metastatic renal cell carcinoma with evidence of metastasis to the brain, adrenal glands, bone, and lungs.

    CONCLUSIONS: To the best of our knowledge, renal malignancy presenting as syndrome of inappropriate antidiuretic hormone secretion and Leser-Trélat concurrently is rare. The causes of hyponatremia in the elderly, approach to investigation, and value as a poor prognostic marker in malignancy are highlighted. We also discuss Leser-Trélat syndrome, its pathophysiology, and its possible implications on clinical practice.

    Matched MeSH terms: Kidney Neoplasms/pathology
  12. Yap NY, Ong TA, Morais C, Pailoor J, Gobe GC, Rajandram R
    Cell Biol Int, 2019 Jun;43(6):715-725.
    PMID: 31062478 DOI: 10.1002/cbin.11150
    Renal cell carcinoma (RCC) is one of the most lethal urogenital cancers and effective treatment of metastatic RCC remains an elusive target. Cell lines enable the in vitro investigation of molecular and genetic changes leading to renal carcinogenesis and are important for evaluating cellular drug response or toxicity. This study details a fast and easy protocol of establishing epithelial and fibroblast cell cultures or cell lines concurrently from renal cancer nephrectomy tissue. The protocol involves mechanical disaggregation, collagenase digestion and cell sieving for establishing epithelial cells while fibroblast cells were grown from explants. This protocol has been modified from previous published reports with additional antibiotics and washing steps added to eliminate microbial contamination from the surgical source. Cell characterisation was carried out using immunofluorescence and quantitative polymerase chain reaction. Eleven stable epithelial renal tumour cell lines of various subtypes, including rare subtypes, were established with a spontaneous immortalisation rate of 21.6% using this protocol. Eight fibroblast cell cultures grew successfully but did not achieve spontaneous immortalisation. Cells of epithelial origin expressed higher expressions of epithelial markers such as pan-cytokeratin, cytokeratin 8 and E-cadherin whereas fibroblast cells expressed high α-smooth muscle actin. Further mutational analysis is needed to evaluate the genetic or molecular characteristics of the cell lines.
    Matched MeSH terms: Kidney Neoplasms/pathology
  13. Syafruddin SE, Rodrigues P, Vojtasova E, Patel SA, Zaini MN, Burge J, et al.
    Nat Commun, 2019 03 11;10(1):1152.
    PMID: 30858363 DOI: 10.1038/s41467-019-09116-x
    Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.
    Matched MeSH terms: Kidney Neoplasms/pathology
  14. Mohtarrudin N, Ghazali R, Md Roduan MR
    Malays J Pathol, 2018 Dec;40(3):313-318.
    PMID: 30580362
    INTRODUCTION: Cyclooxygenase-2 (COX-2) promotes carcinogenesis by inducing proliferation and angiogenesis while decreasing apoptosis and immunosuppressive activity. It is overexpressed in many malignancies including renal cell carcinoma (RCC). The aim of this study was to investigate COX-2 expression in clear cell RCC and its association with tumour grades and demographic parameters.

    MATERIALS AND METHODS: Thirty-six clear cell RCC cases were selected. There were 21 (58.3%) men and 15 (41.7%) women with median age of 56.6 years (range: 16-74 years). Chinese constituted 16 (44.4%) of the cases; Malays 14 (38.9%) cases and Indian 6 (16.7%) cases. There were 6 (16.7%) grade 1, 20 (55.6%) grade 2, 10 (27.8%) grade 3 and none was grade 4. The paraffin embedded tissues were cut at 4 μm thick and stained with COX-2 monoclonal antibody.

    RESULTS: Eighteen (50%) of the RCC cases were immunopositive, of which all showed strong positivity. The immunopositive cases showed cytoplasmic membrane positivity.

    CONCLUSION: There was no significant association between COX-2 expression with grade, age, sex and ethnicity (p=0.457, p=0.054, p=0.389 and p=0.568 respectively). Strong positivity of COX-2 suggest that COX-2 may play a role in cell proliferation and in carcinogenesis.

    Matched MeSH terms: Kidney Neoplasms/pathology
  15. Ng KL, Yap NY, Rajandram R, Small D, Pailoor J, Ong TA, et al.
    Pathology, 2018 Aug;50(5):511-518.
    PMID: 29935727 DOI: 10.1016/j.pathol.2018.03.003
    Better characterisation and understanding of renal cell carcinoma (RCC) development and progression lead to better diagnosis and clinical outcomes. In this study, expression of nuclear factor-kappa B (NF-κB) subunits: p65 (RelA), p105/p50, p100/p52, and cRel in RCC tissue were compared with corresponding normal kidney, along with tumour characteristics and survival outcome. Ninety-six cases of RCC with paired normal kidney were analysed. Clinicopathological data, demographics and survival data were available. Immunohistochemistry (IHC) for NF-κB subtypes was analysed using the Aperio digital pathology system for overall cellular expression and localisation. The prognostic cancer-specific survival value of the subunits in RCC patients was analysed. Approximately 50% of patients had clinical stage T1, with 22 patients having metastases at presentation. RCC subtypes were: clear cell (n = 76); papillary (n = 11); chromophobe (n = 5); clear cell tubulopapillary (n = 3); and one multilocular cystic RCC. Median follow up was 54.5 months (0.2-135), with 28 deaths at time of analysis. NF-κB p65 had higher overall and nuclear expressions, with lower overall and nuclear expressions of p50, p52 and cRel in RCC compared with normal kidney. Higher expressions of p65 (nuclear), p52 (overall and nuclear) and p50 (overall) correlated significantly with worse cancer-specific survival. This is the first large series of analysis of expression of NF-κB subunits in RCC. Especially with regards to the less studied subunits (p52, p50, cRel), our results allow a better understanding the role of NF-κB in RCC development and progression, and may pave the way for future targeted NF-κB subunit specific therapies.
    Matched MeSH terms: Kidney Neoplasms/pathology
  16. Ng KL, Del Vecchio SJ, Samaratunga H, Morais C, Rajandram R, Vesey DA, et al.
    Pathology, 2018 Aug;50(5):504-510.
    PMID: 29970253 DOI: 10.1016/j.pathol.2018.01.007
    One of the challenges in differentiating chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) is overlapping morphology between the two subtypes. The aim of this study was to investigate the usefulness of expression of leptin (Ob) and its receptor (ObR) in discriminating chRCC from RO. Sections from paraffin-embedded, formalin-fixed tumour nephrectomy specimens of 45 patients, made up of 30 chRCC (15 eosinophilic variant and 15 non-eosinophilic variant) and 15 RO, were used in this study. Samples (30) of clear cell RCC (ccRCC), the most common histological subtype, were used to verify staining patterns found by others in our cohort of Australasian patients. Matched morphologically normal non-cancer kidney tissues were included for each specimen. Sections were batch-immunostained using antibodies against Ob and ObR. Stained sections were digitally scanned using Aperio ImageScope, and the expression pattern of Ob and ObR was studied. In this cohort, male to female ratio was 2:1; median age was 64 (45-88 years); and median tumour size was 3.8 cm (range 1.2-18 cm). There were 47 (62.7%) T1, seven T2, 20 T3 and one T4 stage RCC. Two patients with ccRCC presented with metastases. Nuclear expression of Ob was significantly higher in RO compared with chRCC. The increased nuclear expression of Ob in RO compared with chRCC may be a useful aid in the difficult histological differentiation of RO from chRCC, especially eosinophilic variants of chRCC.
    Matched MeSH terms: Kidney Neoplasms/pathology
  17. Rodrigues P, Patel SA, Harewood L, Olan I, Vojtasova E, Syafruddin SE, et al.
    Cancer Discov, 2018 Jul;8(7):850-865.
    PMID: 29875134 DOI: 10.1158/2159-8290.CD-17-1211
    Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states.Significance: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 850-65. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 781.
    Matched MeSH terms: Kidney Neoplasms/pathology
  18. Son HJ, Lee H, Kim JH, Yu IK, Han HY
    Malays J Pathol, 2018 Apr;40(1):73-78.
    PMID: 29704388
    Progressively transformed germinal centers (PTGC) is a benign process characterised by a morphological variant of reactive follicular hyperplasia in lymph nodes. It was recently shown that some cases of PTGC are associated with IgG4-related disease (IgG4-RD) or increased IgG4 plasma cells. Five years ago, a 57-year-old woman presented with enlargement of multiple lymph nodes in the left parotid, submandibular, and neck areas, pathologically diagnosed as PTGC after excisional biopsy. Since then, she has experienced numbness in her extremities, especially the left shoulder and arm, pruritus on the left side of the face and intermittent facial palsy, for which she has been receiving regular symptomatic treatment. Recently the patient developed diabetes mellitus (approximately seven months ago). In routine follow-up scans, a mass was detected in left kidney and magnetic resonance imaging of the abdomen prior to surgery revealed a slightly enhanced bulky mass replacing the pancreatic tail and uncinate process. The mass in left kidney was diagnosed as clear cell renal cell carcinoma, and the pathological features of the pancreatic lesion were those of IgG4-related chronic fibrosing pancreatitis. Retrograde examination of the neck lymph node diagnosed as PTGC showed increased deposition of IgG4-positive plasma cells.
    Matched MeSH terms: Kidney Neoplasms/pathology
  19. Tan GC, Prasad V
    Int. J. Surg. Pathol., 2018 Feb;26(1):34.
    PMID: 28508688 DOI: 10.1177/1066896917709946
    Matched MeSH terms: Kidney Neoplasms/pathology*
  20. Shepherd ARH, Hoh IMY, Goh EH, Cohen PA, Steele D
    ANZ J Surg, 2017 Dec;87(12):1054-1056.
    PMID: 25962888 DOI: 10.1111/ans.13155
    Matched MeSH terms: Kidney Neoplasms/pathology*
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