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Fulltext Decreased Expression of Inhibitor of Caspase-Activated DNase (ICAD) in Renal Cell Carcinoma - Tissue Microarray of Human Samples

Rajandram R, Razack AH, Ng KL, Gobe GC

J Kidney Cancer VHL, 2016;3(1):1-11.
PMID: 28326275 DOI: 10.15586/jkcvhl.2016.47

Although primary localised tumours of renal cell carcinoma (RCC) can be treated relatively successfully with surgery, metastatic RCC has poor prognosis because of late diagnosis and resistance to therapies. In the present study, we were interested in profiling the protein expression of "inhibitor of caspase-activated DNase" (ICAD), an apoptosis inhibitor, in kidney cancer and its paired normal kidney. Immunohistochemistry with automated batch staining and morphometry using digital pathology were used to compare ICAD in 121 RCC specimens with their paired normal kidney tissue. Tissue microarray of formalin-fixed, paraffin-embedded archival tissue was used. Intensity and localisation of ICAD were compared between normal and cancer samples, and against grading within the cancers. The results demonstrated that, in this cohort, ICAD was highly expressed in the proximal tubular epithelium of normal kidney, and significantly decreased in clear cell RCC tissue (p < 0.05) as well as other subtypes of RCC (p < 0.01) compared with normal kidney. There was a tendency towards nuclear localisation of ICAD in clear cell RCC, but not in other subtypes of RCC. No significant association was found between ICAD intensity and grade of RCC. In summary, down-regulation of ICAD occurs in RCC. ICAD normally inhibits DNA fragmentation and apoptosis; thus, its down-regulation was unexpected in a cancer known for its resistance to apoptosis. However, these RCC samples were from primary, not metastatic, RCC sites, and down-regulated ICAD may be part of a progressive pathway that promotes RCC metastasis.

Matched MeSH terms: Kidney Neoplasms
Fulltext Rapidly enlarging renal tumor during pregnancy: diagnostic and management dilemma

Tiang KW, Ng KL, Vega-Vega A, Wood S

J Kidney Cancer VHL, 2014;1(1):12-16.
PMID: 28326245 DOI: 10.15586/jkcvhl.2014.6

Urological tumors diagnosed during pregnancy are rare. However, the incidence seems to be increasing largely due to advancements in modern imaging techniques and improved antenatal care. The diagnosis and management of renal tumors during pregnancy poses a dilemma to clinicians. This case report highlights the challenges in managing a large chromophobe renal cell carcinoma in a young primigravida patient. Proper antenatal assessment, a multidisciplinary team approach and appropriate discussion with patient are important determinants to achieve the best clinical outcomes for both the mother and the baby.

Matched MeSH terms: Kidney Neoplasms
Fulltext An uncommon and insidious presentation of renal cell carcinoma with tumor extending into the inferior vena cava and right atrium: a case report

Lu HT, Chong JL, Othman N, Vendargon S, Omar S

J Med Case Rep, 2016 May 03;10(1):109.
PMID: 27142514 DOI: 10.1186/s13256-016-0888-5

BACKGROUND: Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and it tends to metastasize. Renal cell carcinoma involves the inferior vena cava in approximately 15% of cases and it rarely extends into the right atrium. A majority of renal cell carcinoma are detected as incidental findings on imaging studies obtained for unrelated reasons. At presentation, nearly 25% of patients either have distant metastases or significant local-regional disease with no symptoms that can be attributed to renal cell carcinoma.
CASE PRESENTATION: A 64-year-old Indian male with a past history of coronary artery bypass graft surgery, congestive heart failure, and diabetes mellitus complained of worsening shortness of breath for 2 weeks. Incidentally, a transthoracic echocardiography showed a "thumb-like" mass in his right atrium extending into his right ventricle through the tricuspid valve with each systole. Abdomen magnetic resonance imaging revealed a heterogenous lobulated mass in the upper and mid-pole of his right kidney with a tumor extending into his inferior vena cava and right atrium, consistent with our diagnosis of advanced renal cell carcinoma which was later confirmed by surgical excision and histology. Radical right nephrectomy, lymph nodes clearance, inferior vena cava cavatomy, and complete tumor thrombectomy were performed successfully. Perioperatively, he did not require cardiopulmonary bypass or deep hypothermic circulatory arrest. He had no recurrence during the follow-up period for more than 2 years after surgery.
CONCLUSIONS: Advanced extension of renal cell carcinoma can occur with no apparent symptoms and be detected incidentally. In rare circumstances, atypical presentation of renal cell carcinoma should be considered in a patient presenting with right atrial mass detected by echocardiography. Renal cell carcinoma with inferior vena cava and right atrium extension is a complex surgical challenge, but excellent results can be obtained with proper patient selection, meticulous surgical techniques, and close perioperative patient care.

Matched MeSH terms: Kidney Neoplasms/surgery
Fulltext Syndrome of inappropriate antidiuretic hormone secretion and Leser-Trélat syndrome as uncommon paraneoplastic manifestations of renal malignancy - a geriatric experience: a case report

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/complications*; Kidney Neoplasms/pathology
Superior vena caval syndrome secondary to metastatic renal cell carcinoma

Lim NK, Aik OT, Meng LL, Htun TH, Razack AH

J Coll Physicians Surg Pak, 2014 Mar;24 Suppl 1:S68-70.
PMID: 24718014 DOI: 03.2014/JCPSP.S68S70

Superior vena caval syndrome (SVCS) is a debilitating condition attributed to malignancy in more than 70% of cases. However, solitary head and neck metastases arising from renal cell carcinomas without evidence of disease elsewhere are rare. We report a case of renal cell carcinoma presenting as a rapidly growing right cervical lymph node with compression on the subclavian vein causing superior vena caval syndrome (SVCS). There was pulmonary embolism as well. Biopsy of the neck mass confirmed metastatic clear cell carcinoma with primary found in the (L) kidney. The patient had partial response to focussed radiotherapy to neck mass and Sunitinib (tyrosine kinase inhibitor) before succumbing to the disease.

Matched MeSH terms: Kidney Neoplasms/pathology*; Kidney Neoplasms/surgery
Secondary B-cell acute lymphoblastic leukemia following Wilms' tumor: clinical and in vitro chemosensitivity studies

Ariffin H, Muthukkumaran T, Stanslas J, Sabariah AR, Veerasekaran N, Lin HP

Leuk Lymphoma, 2005 Aug;46(8):1233-7.
PMID: 16085568

We report the clinical features and in vitro chemosensitivity assay findings of a 13-year-old girl who developed secondary B-cell acute lymphoblastic leukemia (ALL) 7 years after a diagnosis of Wilms' tumor. The patient was treated using the Berlin - Frankfurt - Muenster (BFM) ALL chemotherapy protocol with poor response to initial therapy before succumbing to sepsis. An in vitro chemosensitivity assay on her peripheral blood lymphoblasts was performed while she was undergoing induction therapy and showed a high level of resistance to drugs commonly used for ALL therapy, e.g. steroids, anthracyclines, vincristine and L-asparaginase. The mechanism of chemoresistance was not elicited, but was probably not related to P-glycoprotein (P-gp) over-expression. We believe that the in vitro chemosensitivity assay is a good indicator of cellular response to chemotherapy and may provide reliable information for the basis of the selection of drugs to be used for the treatment of similarly rare patients rather than relying on "standard" protocols.

Matched MeSH terms: Kidney Neoplasms/complications*; Kidney Neoplasms/diagnosis; Kidney Neoplasms/drug therapy
Role of leptin as a biomarker for early detection of renal cell carcinoma? No evidence from a systematic review and meta-analysis

Perumal K, Huin WK, Yap NY, Ong TA, Gobe GC, Rajandram R

Med Hypotheses, 2019 Aug;129:109239.
PMID: 31371068 DOI: 10.1016/j.mehy.2019.109239

Renal cell carcinoma (RCC) is the commonest from of renal neoplasm. Although surgery is a successful curative treatment for localized RCC, most patients are diagnosed with advanced or metastatic RCC, which has poor prognosis. RCC is classified by stage and grade using tissue samples. Whilst these provide good prognostic information, they are not very useful for early detection. Proteins that are dysregulated in patient's serum can be a valuable alternative and less invasive biomarker for early detection of the disease. For this reason, a hypothesis was formed that leptin is a possible biomarker for early detection and prognostication of RCC. The literature has disparate results on the usefulness of leptin as a biomarker for the early detection of RCC. Hence, a systematic review and a meta-analysis was carried out to investigate whether serum leptin could be a reliable diagnostic and prognostic factor in RCC patients. Literature on the available cohort and case-control studies on serum leptin in RCC was searched in electronic databases and included to evaluate this adipokine in the progression of RCC. The relevant studies were evaluated for the diagnostic and prognostic value of leptin in RCC patients. Overall, only 6 original research studies matched selection criteria and were included for meta-analysis. This study was hypothesised that; leptin might be a useful biomarker for early detection and prognostication of RCC. However, the data were presented in this study did not support our hypothesis. Serum leptin levels in RCC patients do not strongly associate with the development or progression of RCC, thus cannot act as a biomarker for early detection in RCC in patients. Extending our hypothesis further to include levels of obesity and RCC development may be worthwhile, but studies are currently limited.

Matched MeSH terms: Kidney Neoplasms
Probucol modulates iron nitrilotriacetate (Fe-NTA)-dependent renal carcinogenesis and hyperproliferative response: diminution of oxidative stress

Iqbal M, Okazaki Y, Okada S

Mol Cell Biochem, 2007 Oct;304(1-2):61-9.
PMID: 17487455

Probucol is a clinically used cholesterol-lowering drug, with pronounced antioxidant properties. We have reported previously, that dietary supplementation of probucol enhances NAD(P)H:quinone reductase (Iqbal M, Okada S (2003) Pharmacol Toxicol 93:259-263) and inhibits Fe-NTA induced lipid peroxidation and DNA damage in vitro (Iqbal M, Sharma SD, Oakada (2004) Redox Rep 9:167-172). Further to this, in the present study, we evaluated the modulatory effect of probucol on iron nitrilotriacetae (Fe-NTA) dependent renal carcinogenesis, hyperproliferative response and oxidative stress. In Fe-NTA alone treated group, a 20% renal cell tumor incidence was recorded whereas, in N-diethylnitrosamine (DEN)-initiated and Fe-NTA promoted animals, the percentage tumor incidence was increased to 70% as compared with untreated controls. No tumor incidence was recorded in DEN-initiated, nonpromoted group. Diet supplemented with 1.0% probucol fed prior to, during and after Fe-NTA treatment in DEN-initiated animals afforded >65% protection in renal cell tumor incidence. Probucol fed diet pretreatment also resulted a significant and dose dependent inhibition of Fe-NTA induced renal ornithine decarboxylase (ODC) activity. In oxidative stress studies, Fe-NTA alone treatment enhanced lipid peroxidation, accompanied by a decrease in the level of GSH, activities of antioxidants and phase II metabolizing enzymes in kidney concomitant with histolopathological changes. These changes were significantly and dose-dependently alleviated by probucol fed diet. From this data, it can be concluded that probucol can modulates toxic and tumor promoting effects of Fe-NTA and can serve as a potent chemopreventive agent to suppress oxidant induced tissue injury and carcinogenesis, in addition to being a cholesterol lowering and anti-atherogenic drug.

Matched MeSH terms: Kidney Neoplasms/chemically induced*; Kidney Neoplasms/pathology; Kidney Neoplasms/prevention & control
Fulltext A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma

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/genetics*; Kidney Neoplasms/pathology
Fulltext Brewers' Rice: A By-Product from Rice Processing Provides Natural Hepatorenal Protection in Azoxymethane-Induced Oxidative Stress in Rats

Tan BL, Norhaizan ME, Hairuszah I, Hazilawati H, Roselina K

Oxid Med Cell Longev, 2015;2015:539798.
PMID: 26257841 DOI: 10.1155/2015/539798

Brewers' rice, which is known locally as temukut, is a mixture of broken rice, rice bran, and rice germ. Our present study was designed to identify the effect of brewers' rice on the attenuation of liver and kidney damage induced by azoxymethane (AOM). Alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST), creatinine, and urea were evaluated to understand potential hepatoprotective effects and the ability of brewers' rice to attenuate kidney pathology induced by AOM treatment. Liver and kidney tissues were evaluated by hematoxylin and eosin (H&E) staining. Overall analyses revealed that brewers' rice improved the levels of serum markers in a manner associated with better histopathological outcomes, which indicated that brewers' rice could enhance recovery from hepatocyte and kidney damage. Taken together, these results suggest that brewers' rice could be used in future applications to combat liver and kidney disease.

Matched MeSH terms: Kidney Neoplasms/chemically induced; Kidney Neoplasms/pathology; Kidney Neoplasms/prevention & control*
Sorafenib in renal cell carcinoma

Davoudi ET, bin-Noordin MI, Javar HA, Kadivar A, Sabeti B

Pak J Pharm Sci, 2014 Jan;27(1):203-8.
PMID: 24374450

Cancer is among most important causes of death in recent decades. Whoever the renal cell carcinoma incidence is low but it seems it is more complicated than the other cancers in terms of pathophysiology and treatments. The purpose of this work is to provide an overview and also deeper insight to renal cell carcinoma and the steps which have been taken to reach more specific treatment and target therapy, in this type of cancer by developing most effective agents such as Sorafenib. To achieve this goal hundreds of research paper and published work has been overviewed and due to limitation of space in a paper just focus in most important points on renal cell carcinoma, treatment of RCC and clinical development of Sorafenib. The information presented this paper shows the advanced of human knowledge to provide more efficient drug in treatment of some complicated cancer such as RCC in promising much better future to fight killing disease.

Matched MeSH terms: Kidney Neoplasms/drug therapy*
Nuclear factor-kappa B subunits and their prognostic cancer-specific survival value in renal cell carcinoma patients

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/metabolism*; Kidney Neoplasms/mortality; Kidney Neoplasms/pathology
Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance

Rajandram R, Yap NY, Pailoor J, Razack AH, Ng KL, Ong TA, et al.

Pathology, 2014 Oct;46(6):518-22.
PMID: 25158810 DOI: 10.1097/PAT.0000000000000145

Renal cell carcinoma (RCC) generally has a poor prognosis because of late diagnosis and metastasis. We have previously described decreased tumour necrosis factor receptor-associated factor-1 (TRAF-1) in RCC compared with paired normal kidney in a patient cohort in Australia. In the present study, TRAF-1 expression in clear cell RCC (ccRCC) and normal kidney was again compared, but in a cohort from University Malaya Medical Centre. Serum TRAF-1 was also evaluated in RCC and normal samples.Immunohistochemistry with automated batch staining and Aperio ImageScope morphometry was used to compare TRAF-1 in 61 ccRCC with paired normal kidney tissue. Serum from 15 newly diagnosed and untreated ccRCC and 15 healthy people was tested for TRAF-1 using ELISA.In this cohort, TRAF-1 was highly expressed in proximal tubular epithelium of normal kidney, and significantly decreased in ccRCC tissue (p

Matched MeSH terms: Kidney Neoplasms
Clear cell sarcoma of kidney: report of the first Malaysian case

Looi LM, Cheah PL, Lin HP

Pathology, 1992 Jan;24(1):34-6.
PMID: 1374551

Clear cell sarcoma of kidney (CCSK) is a rare but distinct tumor of childhood frequently confused with Wilms' tumor (nephroblastoma). It has a characteristic histology, a marked predilection for metastasis to bone, and an aggressive clinical course with a high relapse rate in spite of surgical excision, chemotherapy and radiotherapy. We report the first histologically proven CCSK in a Malaysian patient. This was an 8-mth-old Malay boy who was clinically diagnosed to have stage I Wilms' tumor. Despite treatment, he developed multiple metastases 10 mths after initial presentation and died soon after. Emphasis is placed on recognizing this entity in view of (1) its naturally aggressive behaviour and (2) the prospect of improving prognosis with currently recommended intensified chemotherapeutic regimes. Its immunohistochemical profile of vimentin-positivity and negativity for epithelial membrane antigen, cytokeratin and Factor-8 related antigen is more in favour of a mesenchymal or glomerular origin than a tubular or vascular origin.

Matched MeSH terms: Kidney Neoplasms/diagnosis; Kidney Neoplasms/epidemiology*; Kidney Neoplasms/chemistry
Implications of p53 protein expression in clear cell sarcoma of the kidney

Cheah PL, Looi LM

Pathology, 1996 Aug;28(3):229-31.
PMID: 8912350

Eight histologically-confirmed cases of clear cell sarcoma of the kidney (CCSK) were studied for possible mutations in the p53 tumor suppressor gene by the immunohistochemical demonstration of mutant p53 proteins using a monoclonal (DO7: Dako) and a polyclonal (AB565: Chemicon) antibody to p53 protein. All cases exhibited p53 protein nuclear immunopositivity, although in varying numbers of tumor cells and with different staining intensities. p53 protein (DO7 or AB565) was expressed in < 25% of the tumor cells in four (50%) of the cases, including the one case with a known long term survival of 13 years from the time of diagnosis. The other tumors showed p53 protein immunopositivity in > 25% of the tumor cells when stained with either DO7 or AB565 or both. The intensity of staining, graded on visual impression into weak, moderate or strong, did not correlate well with the ratio of positive staining tumor cells. While this study is unable to clarify the relative prevalence and importance of p53 mutational events in the pathogenesis of this aggressive renal tumor of childhood, it is reasonably suggestive that alterations in the p53 tumor suppressor gene do occur in CCSK.

Matched MeSH terms: Kidney Neoplasms/genetics; Kidney Neoplasms/metabolism*; Kidney Neoplasms/pathology
An immunohistochemical study comparing clear cell sarcoma of the kidney and Wilms' tumor

Looi LM, Cheah PL

Pathology, 1993 Apr;25(2):106-9.
PMID: 8396229

This study explores immunohistochemical characteristics that may be of diagnostic value in differentiating clear cell sarcoma of the kidney (CCSK) from Wilms' tumor (WT) and may provide some insight into the histogenesis of CCSK. Formalin-fixed, paraffin-embedded sections of 8 CCSK and 9 WT were stained, using the standard avidin-biotin peroxidase complex method, for vimentin (VIM), Factor-8 related antigen (F8A), epithelial membrane antigen (EMA), desmin (DES), S-100 protein and Mac 387. CCSK cells consistently exhibited moderate to strong diffuse cytoplasmic positivity for VIM and were negative for F8A, EMA, DES, S-100 and Mac 387. In contrast, only patchy groups of stromal cells and primitive glomeruloid structures in WT exhibited VIM-positivity. Blastemal cells were VIM-negative. Stromal cells with rhabdomyomatous differentiation exhibited cytoplasmic positivity for DES. Epithelial cells of maturing tubular structures showed EMA-positivity whereas immature tubular structures were EMA-negative. Neither blastemal, stromal nor epithelial elements in WT were positive for F8A, S-100 or Mac 387. Podocytes and mesangial cells of glomeruli in 3 mid-trimester human abortuses (controls) exhibited moderate to strong VIM-positivity. The importance of differentiating CCSK from WT has been repeatedly emphasized because of its poorer prognosis and the necessity of adding Adriamycin to the chemotherapeutic regime. The consistent VIM-positivity of CCSK cells can be a useful feature in differentiating it from "blastemal-predominant" WT, with which it is often confused. Although vimentin expression by CCSK cells is consistent with a mesenchymal character, the possibility of a histogenetic link with glomerular podocytes or mesangial cells should also be considered.

Matched MeSH terms: Kidney Neoplasms/pathology*; Kidney Neoplasms/chemistry
Leptin and its receptor: can they help to differentiate chromophobe renal cell carcinoma from renal oncocytoma?

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/diagnosis; Kidney Neoplasms/metabolism*; Kidney Neoplasms/pathology
Fulltext Expression of protease activated receptor-2 is reduced in renal cell carcinoma biopsies and cell lines

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/genetics; Kidney Neoplasms/metabolism*; Kidney Neoplasms/pathology*
Fulltext Endobronchial metastasis from resected renal cell carcinoma causing total lung collapse

Poh ME, Liam CK, Pang YK, Chua KT

Respirol Case Rep, 2013 Dec;1(2):26-7.
PMID: 25473534 DOI: 10.1002/rcr2.16

We report a man presenting with dyspnea, cough, and hemoptysis due to left lung collapse from an endobronchial tumor obstructing the left main bronchus. Endobronchial biopsy of the tumor showed renal cell carcinoma, identical to a previous specimen of renal cell carcinoma removed by a radical left nephrectomy five years ago. The endobronchial tumor was removed by snare diathermy through a flexible bronchoscope, following which his symptoms resolved and the left lung re-expanded. Endobronchial metastasis from renal cell carcinoma is rare and can mimic obstruction from other endobronchial etiologies, such as bronchogenic carcinoma. Total lung collapse as a result is even more uncommon, although atelectasis is well described. Endobronchial techniques, such as snare diathermy, can relieve obstruction, providing symptom palliation even in advanced disease.

Matched MeSH terms: Kidney Neoplasms
Fulltext Metastatic neuroendocrine tumor of small cell type in a kidney transplant recipient

Mohd Kamil A, Draman CR, Seman MR, Kalavathy R, Mubarak MY

Saudi J Kidney Dis Transpl, 2016 Jul-Aug;27(4):787-90.
PMID: 27424699 DOI: 10.4103/1319-2442.185259

Malignancy is a significant long-term complication of successful renal transplantation. Not only the rate is higher but also cases are highly aggressive. We report a case of metastatic, small cell, neuroendocrine tumor in a post-renal transplant patient with progressive left inguinal nodes and right lumbar swellings. He had a remarkably elevated serum lactate dehydrogenase levels with multiple metastatic masses in the left inguinal, left iliac fossa, and right lower abdominal wall on abdominal computed tomography scan. Excisional biopsy of a left inguinal node revealed extensive infiltration with malignant cells in it. Immunohistochemistry staining was positive for synaptophysin, prostatic specific antigen, and CD56. While the primary small cell carcinoma of genitourinary organs is rare, the case illustrates the highly aggressive nature of the disease in a kidney transplant recipient.

Matched MeSH terms: Kidney Neoplasms

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