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

Ng, Keng Lim; Morais, Christudas; Bernard, Anne; Saunders, Nicholas A.; Samaratunga, Hemamali; Gobé, Glenda C.; Wood, Simon

doi:10.1136/jclinpath-2015-203585

Cited by 49 publications

(46 citation statements)

References 56 publications

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“…Altogether, accumulating evidences consistently support that CAV1 plays an important role in cancer progression – the specific nature of which seems to depend on several factors, including cancer type and stage, lesions on CAV1 or its associated genes, its protein expression level and subcellular localisation. The fact that CAV1 could serve as a clinical biomarker [45, 46] further emphasizes its importance in cancer. However, despite knowledge of its expression pattern and roles in different cancers, it is still unclear whether CAV1 expression is a property that accompanies or directly drives altered metabolism, or if changes in energy balance modulate CAV1 level towards or against cancer progression.…”

Section: Relevance Of Caveolin-1 In Cancermentioning

confidence: 99%

Caveolin-1 in the regulation of cell metabolism: a cancer perspective

Nwosu¹,

Ebert²,

Dooley³

et al. 2016

Mol Cancer

182

128

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Caveolin-1 (CAV1) is an oncogenic membrane protein associated with endocytosis, extracellular matrix organisation, cholesterol distribution, cell migration and signaling. Recent studies reveal that CAV1 is involved in metabolic alterations – a critical strategy adopted by cancer cells to their survival advantage. Consequently, research findings suggest that CAV1, which is altered in several cancer types, influences tumour development or progression by controlling metabolism. Understanding the molecular interplay between CAV1 and metabolism could help uncover druggable metabolic targets or pathways of clinical relevance in cancer therapy. Here we review from a cancer perspective, the findings that CAV1 modulates cell metabolism with a focus on glycolysis, mitochondrial bioenergetics, glutaminolysis, fatty acid metabolism, and autophagy.

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Section: Relevance Of Caveolin-1 In Cancermentioning

confidence: 99%

Caveolin-1 in the regulation of cell metabolism: a cancer perspective

Nwosu¹,

Ebert²,

Dooley³

et al. 2016

Mol Cancer

182

128

View full text Add to dashboard Cite

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“…Although several existing prognostic systems and models have been established with considerable prognostic ability, they still need to be improved. In recent years, there has been a growing interest in identifying novel tumor markers not only for diagnostic purposes but also to improve the prediction of prognosis 3,4. Combining the molecular biomarkers with conventional models might provide more individualized diagnosis and treatment based on molecular characteristics of the tumor 5–7…”

Section: Introductionmentioning

confidence: 99%

High expression of Aldolase A predicts poor survival in patients with clear-cell renal cell carcinoma

Na¹,

Li²,

Xu³

et al. 2017

TCRM

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BackgroundAldolase A (ALDOA) is a glycolytic enzyme that drives the glycolytic metabolic pathway in mammalian cells. The overexpression of ALDOA was observed in a variety of cancers including clear-cell renal cell carcinoma (ccRCC). However, little was known about the clinicopathological significance and prognostic value of ALDOA in ccRCC patients.MethodsThe expression of ALDOA was detected using immunohistochemical staining in 162 formalin-fixed, paraffin-embedded ccRCC sections. Prognostic outcomes correlated with ALDOA were examined using Kaplan–Meier analysis and the Cox proportional hazards model.ResultsIn patients with ccRCC, increased cytoplasmic ALDOA expression was positively associated with tumor size (P=0.021), TNM stages (P=0.034), lymph node metastasis (P=0.020), and overall survival (OS) (P<0.001). Kaplan–Meier analysis showed that high cytoplasmic expression of ALDOA was associated with a statistically significant lower OS (P<0.001). Multivariate analysis demonstrated that ALDOA expression was an independent and significant prognostic factor (HR =3.561, 95% CI =1.715–7.396, P=0.001). ALDOA expression was not associated with significant prognostic deference in the subgroups of TNM stage I patients or pT1 patients.ConclusionOur results suggest that ALDOA expression is an independent prognostic factor for OS in patients with ccRCC.

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“…Nevertheless, the CK7 IHC study provided similar results as revealed by our meta-analysis where CK7 has been identified as the most studied IHC biomarker in the differentiation between chRCC and RO (Ng et al 2016). From this meta-analysis, we also recommended CK7 as part of our panel of IHC biomarkers than can be useful in differentiating chRCC from RO.…”

Section: Cytokeratinsupporting

confidence: 72%

“…Therefore, a metaanalysis was conducted to answer this question. This meta-analysis has been published (Ng et al 2016) (Appendix 6).…”

Section: Meta-analysis Of Immunohistochemical Biomarkers That Differementioning

confidence: 99%

“…Therefore, S100A1 is another reproducible IHC biomarker from a panel of IHC biomarkers,that can differentiate RO from chRCC (Ng et al 2016). Other authors have suggested a panel of CK7, S100A1 and claudin 8 (Kim et al 2009) and the utility of cluster analysis of S100A1 and CK7 (Carvalho et al 2011) which could discriminate the two entities.…”

Section: S100 Calcium-binding Protein A1mentioning

confidence: 99%

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Identification of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma through molecular profiling of renal tumours

Ng¹

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There is increasing detection of renal tumours, especially small renal masses largely due to widespread availability of radiological imaging modalities. However, imaging techniques and renal lesion biopsies cannot accurately define malignant from benign renal tumours.Therefore such indeterminate renal tumours undergo surgical resection. Unfortunately a significant proportion of resected renal tumours turn out to be benign on histopathological diagnosis. The impact of this scenario is the morbidities of unnecessary surgery and loss of valuable nephrons with the associated increased risk of chronic kidney disease and cardiovascular complications. Reduction of unnecessary surgeries would also translate into decreased costs, and allow for more efficient utilisation of health budgets.Another diagnostic dilemma faced by pathologists is the occasional difficulty in distinguishing some renal tumour subtypes, due to overlapping morphological and histological features. Differentiating malignant chromophobe renal cell carcinoma (chRCC) from benign renal oncocytoma (RO) is one such dilemma. Their correct diagnosis is crucial as prognosis, management and surveillance protocols differ between the two tumour subtypes. Therefore effective and reproducible immunohistochemistry (IHC) biomarkers need to be identified, together with novel biomarkers, through molecular profiling of these tumour subtypes.In Chapter 1, the relevant background, significance of the research topic, literature review, hypothesis and aims of this PhD research were presented. Contents of this chapter have also been published as a review article. The review article provided the clinical presentation, ii explained the diagnostic dilemma, and described the value of current molecular markers to assist in differentiation between chRCC and RO.The aims of this research project were to: 1) identify a panel of IHC biomarkers which can effectively differentiate chRCC from RO through a comprehensive literature search and meta-analysis approach, as well as using some of the research results from my laboratory; 2) analyse the molecular profiles of renal cancers via IHC and morphometry techniques using Biobank. This work involved a significant amount of time and resources throughout the PhD research project, achieved Aim 4 of the thesis, and will be a legacy of this PhD research.Chapter 3 examined the existing IHC biomarkers that have been reported as useful in differentiating chRCC from RO. A meta-analysis and systematic review was conducted in iii this chapter to assess the most effective IHC biomarkers, and it has been published. In summary, we recommended a selection from a panel of IHC biomarkers, namely, amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.In Chapter 4, we investigated the molecular profiles of nuclear factor-κB (NF-κB) subunits in RCC disease. Our results represent the first and largest study to report on the IHC expression of NF-κB subunits (p65, p50, p52, cRel)...

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

Abstract: We recommend a panel of IHC biomarkers of amylase α1A, Wnt-5a, FXYD2, ARPP, CD63, TGFβ1, CK7, S100A1, caveolin-1 and claudin-7 to aid in the differentiation of chRCC and RO.

Cited by 49 publications

References 56 publications

Caveolin-1 in the regulation of cell metabolism: a cancer perspective

Caveolin-1 in the regulation of cell metabolism: a cancer perspective

High expression of Aldolase A predicts poor survival in patients with clear-cell renal cell carcinoma

Identification of immunohistochemical biomarkers that differentiate chromophobe renal cell carcinoma from renal oncocytoma through molecular profiling of renal tumours

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