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A systematic review and meta-analysis of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma

Ng KL, Morais C, Bernard A, Saunders N, Samaratunga H, Gobe G, et al.

J Clin Pathol, 2016 Aug;69(8):661-71.
PMID: 26951082 DOI: 10.1136/jclinpath-2015-203585

Numerous immunohistochemical (IHC) biomarkers have been employed to aid in the difficult differentiation between chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (RO). A systematic review and meta-analysis of the published literature was carried out to summarise and analyse the evidence for discriminatory IHC biomarkers to differentiate the two entities.

Matched MeSH terms: Carcinoma, Renal Cell/diagnosis*
Carbonic anhydrase IX immunohistochemistry has potential to predict renal cell carcinoma outcomes: A systematic review and meta-analyses

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: Carcinoma, Renal Cell/diagnosis
Fulltext Metastasis within a metastasis to the thyroid: A rare phenomenon

Wong YP, Affandi KA, Tan GC, Muhammad R

Indian J Pathol Microbiol, 2017 9 25;60(3):430-432.
PMID: 28937391 DOI: 10.4103/IJPM.IJPM_287_16

Metastatic disease involving the thyroid gland is uncommon. Solitary thyroid metastases from various primary sites particularly kidney, lung, and breast had been previously described. To the best of our knowledge, metastases from two topographically separate primary malignancies to the thyroid have never been documented hitherto. This is the first reported case of cancer-to-cancer metastasis involving an invasive breast carcinoma metastasized within a metastatic renal cell carcinoma in the nonneoplastic thyroid in a 58-year-old woman. Distinguishing a secondary thyroid metastases from a primary thyroid malignancy is utmost crucial as treatment differs. The possibility of tumor metastases from two separated primaries should always be considered in a tumor exhibiting malignant cell populations with two distinctive histomorphological appearances. The role of immunohistochemistry stains in equivocal cases cannot be overemphasized.

Matched MeSH terms: Carcinoma, Renal Cell/diagnosis*
Fulltext Renal cell carcinoma with proliferative lupus nephritis

Wong KW

BMJ Case Rep, 2015 Jan 16;2015.
PMID: 25596289 DOI: 10.1136/bcr-2014-208060

We report a case of renal cell carcinoma diagnosed after a patient was treated successfully with intravenous cyclophosphamide for her active proliferative lupus nephritis (classes III and V). After the intravenous cyclophosphamide regimen, the patient was asymptomatic with persistent microscopic haematuria, and no proteinuria. The renal cell carcinoma was located on the left kidney; incidentally, this was where the initial renal biopsy was done to diagnose lupus nephritis.

Matched MeSH terms: Carcinoma, Renal Cell/diagnosis
Circulating adiponectin as a biomarker in renal cell carcinoma: a systematic review and meta-analysis

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: Carcinoma, Renal Cell/diagnosis*
Fulltext KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study

Scelo G, Muller DC, Riboli E, Johansson M, Cross AJ, Vineis P, et al.

Clin Cancer Res, 2018 Nov 15;24(22):5594-5601.
PMID: 30037816 DOI: 10.1158/1078-0432.CCR-18-1496

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis.Experimental Design: KIM-1 concentrations were measured in prediagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to 5 years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival.Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 [95% confidence interval (CI), 1.44-2.03, P = 4.1 × 10-23], corresponding to an IRR of 63.3 (95% CI, 16.2-246.9) comparing the 80th to the 20th percentiles of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index, and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver-operating characteristic curve of 0.8 compared with 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (P = 0.0053).Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival. Clin Cancer Res; 24(22); 5594-601. ©2018 AACR.

Matched MeSH terms: Carcinoma, Renal Cell/diagnosis
Fulltext Proptosis: a rare presentation of metastatic renal cell carcinoma

Ho CC, Krishna KK, Praveen S, Goh EH, Lee BC, Zulkifli MZ

Med J Malaysia, 2010 Sep;65(3):229-30.
PMID: 21939176

We present a case of a middle-aged man who was incidentally found to have right renal solid mass while investigating for his left eye proptosis. Computerised tomography (CT) scan confirmed the diagnosis of renal cell carcinoma and the tumour was successfully excised via open surgery. The histopathology examination revealed the 10x7x8 cm mass to be a clear cell type renal cell carcinoma. The rare presentation of this metastatic renal cell carcinoma, its diagnosis and management will be discussed.

Matched MeSH terms: Carcinoma, Renal Cell/diagnosis*
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: Carcinoma, Renal Cell/diagnosis
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: Carcinoma, Renal Cell/diagnosis