Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma

Mathers, Marie E.; Pollock, Anne; Marsh, Colin; O’Donnell, Marie

doi:10.1046/j.1365-2559.2002.01397.x

Cited by 89 publications

(63 citation statements)

References 16 publications

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“…Cytokeratin 7 (CK7) has a firmly established role as a diagnostic marker in renal tumor histopathology, especially because of its distinct staining pattern which is characteristic for chromophobe carcinoma [13,31]. Only a subset (10-15%) of CCRCCs express CK7, and according to some reports, this expression may have an influence on prognosis.…”

Section: Discussionmentioning

confidence: 99%

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Hejnold¹,

Dyduch²,

Białas³

et al. 2014

pjp

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Renal clear cell carcinoma (CCRCC) is an aggressive tumor for which new prognostic factors are needed. It has been suggested that CCRCCs co-expressing P53 and MDM2 could represent a special subgroup; therefore the aim of this study was to explore their immunohistochemical features. The material studied consisted of 470 cases of CCRCC. Immunohistochemistry for MDM2, P53, Ki-67, VEGF-A, VEGF-C, VEGF-D, GLUT1, CA9, and CK 7 was performed on tissue microarrays and assessed semi-quantitatively. On average, 6.6% or 5.3% of cases were P53+/ MDM2+, depending on the P53 antibody used. The mean percentage of Ki-67 positive cells was 0.6% and p53-positive MDM2-positive cases showed significantly higher expression of Ki-67. The other immunohistochemical parameters studied did not differ between p53-positive MDM2-positive cases and the rest of the subtypes studied. Expression of almost all immunohistochemical markers differed with respect to pT stage; only for CA9 was the difference not significant. Furthermore, almost all immunohistochemical markers studied differed with respect to differences in grade; only for GLUT1 was the difference not significant. Our results suggest that with the exception of Ki-67, there are no significant associations between analyzed markers and the double P53+/MDM2+ phenotype.

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Section: Discussionmentioning

confidence: 99%

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Hejnold¹,

Dyduch²,

Białas³

et al. 2014

pjp

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“…Chromophobe RCC strongly and diffusely expresses CD117 in a membranous pattern and is negative for CA-IX expression; CK7 expression is typically diffuse in classic ChRCC but may be patchy, focal, or even negative in the eosinophilic variant. 7,8,83,84 Classic ChRCC is associated with multiple chromosomal losses, and recent molecular data indicate frequent mutations in tumor protein p53 (TP53) and phosphatase and tensin homolog (PTEN), as well as telomerase reverse transcriptase (TERT) promoter alterations 85,86 ; the molecular basis of the eosinophilic variant has not been fully explored, but these tumors typically show fewer chromosomal losses. 85 Genetic predisposition to the development of ChRCC, particularly so-called hybrid oncocytic/chromophobe tumors that show overlapping features of oncocytoma and ChRCC, is seen in patients with Birt-Hogg-Dubé syndrome, which is associated with germline folliculin (FLCN) mutations; these patients often develop multiple, bilateral, oncocytic renal neoplasms, including ChRCC, hybrid oncocytic/chromophobe tumors, and oncocytoma, and may also have characteristic skin (ie, fibrofolliculomas, trichodiscomas) and lung (ie, subpleural cystic blebs) findings.…”

Section: Rcc With Eosinophilic (Oncocytic) Cytoplasmmentioning

confidence: 99%

Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification

Udager

Mehra²

2016

Archives of Pathology &Amp; Laboratory Medicine

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Molecular and morphologic interrogation has driven a much-needed reexamination of renal cell carcinoma (RCC). Indeed, the recently released 2016 World Health Organization classification now recognizes 12 distinct RCC subtypes, as well as several other emerging/provisional RCC entities. From a clinical perspective, accurate RCC classification may have important implications for patients and their families, including prognostic risk stratification, targeted therapeutics selection, and identification for genetic testing. In this review, we provide a conceptual framework for approaching RCC diagnosis and classification by categorizing RCCs as tumors with clear cytoplasm, papillary architecture, and eosinophilic (oncocytic) cytoplasm. The currently recognized 2016 World Health Organization classification for RCC subtypes is briefly discussed, including new diagnostic entities (clear cell papillary RCC, hereditary leiomyomatosis and RCCassociated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, and acquired cystic disease-associated RCC) and areas of evolving RCC classification, such as transcription elongation factor B subunit 1 (TCEB1)-mutated RCC/RCC with angioleiomyoma-like stroma/ RCC with leiomyomatous stroma, RCC associated with anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangement, thyroidlike follicular RCC, and RCC in neuroblastoma survivors. For each RCC subtype, relevant clinical, molecular, gross, and microscopic findings are reviewed, and ancillary studies helpful for its differential diagnosis are presented, providing a practical approach to modern RCC classification.

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“…This is in concordance with other previous works, where in chRCC, there was diffuse cytoplasmic with peripheral enhancement expression while only weak patchy sporadic expression was reported in RO (Bing et al 2013;Mathers et al 2002). In addition, the CK7 expression was weak or absent in most of our ccRCC.…”

Section: Cytokeratinsupporting

confidence: 93%

“…This differential IHC result between positively-stained chRCC versus poorly-stained RO on our Australian cohort of patients provides further validation to other published results (Adley et al 2006a;Leroy et al 2000;Liu et al 2007;Mathers et al 2002). However, there were also some authors who had different results where RO had also prominent CK7 expression when compared to chRCC (Taki et al 1999;Wu et al 2002).…”

Section: Cytokeratinsupporting

confidence: 88%

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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Cytokeratin 7: a useful adjunct in the diagnosis of chromophobe renal cell carcinoma

Abstract: Immunohistochemical staining for cytokeratin 7 appears to be a useful adjunct in the diagnosis of chromophobe renal cell carcinoma, and in distinguishing this tumour from both oncocytoma and conventional renal cell carcinoma.

Cited by 89 publications

References 16 publications

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Selected immunohistochemical features of conventional renal cell carcinomas coexpressing P53 and MDM2

Morphologic, Molecular, and Taxonomic Evolution of Renal Cell Carcinoma: A Conceptual Perspective With Emphasis on Updates to the 2016 World Health Organization Classification

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

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