Large (&gt;3.8 cm) clear cell renal cell carcinomas are morphologically and immunohistochemically heterogeneous

Zaldumbide, Laura; Erramuzpe, Asier; Guarch, Rosa; Cortés, Jesús M.; López, José I.

doi:10.1007/s00428-014-1673-8

Cited by 19 publications

(13 citation statements)

References 35 publications

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“…This fact makes difficult to quantify the nature and extent of ITH, if present, in most CCRCC. Although pathologists recognize by naked eye whitish hard areas related to sarcomatoid transformation, as well as hemorrhagic and/or necrotic foci, there is a significant amount of ITH hidden in apparently homogeneous areas, as recently reported [ 10 – 12 ]. Furthermore, an incomplete tumor sampling may justify the unexpected aggressive behavior that some low-grade CCRCC show [ 12 ].…”

Section: Discussionmentioning

confidence: 95%

“…Although pathologists recognize by naked eye whitish hard areas related to sarcomatoid transformation, as well as hemorrhagic and/or necrotic foci, there is a significant amount of ITH hidden in apparently homogeneous areas, as recently reported [ 10 – 12 ]. Furthermore, an incomplete tumor sampling may justify the unexpected aggressive behavior that some low-grade CCRCC show [ 12 ]. The present work has shown the relationship between cell type and Grade in CCRCC, since a mixture of conventional clear and granular cells determines high tumor Grade (G3/G4) in more than 83 % of cases.…”

Section: Discussionmentioning

confidence: 95%

“…CCRCC ITH has been specifically studied in the last years from a molecular perspective [ 3 , 4 , 7 – 9 ]. However, there are few studies addressing the problem from a clinical routine approach [ 10 – 12 ].…”

Section: Introductionmentioning

confidence: 99%

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Snail heterogeneity in clear cell renal cell carcinoma

et al. 2016

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BackgroundIntratumor heterogeneity may be responsible of the unpredictable aggressive clinical behavior that some clear cell renal cell carcinomas display. This clinical uncertainty may be caused by insufficient sampling, leaving out of histological analysis foci of high grade tumor areas. Although molecular approaches are providing important information on renal intratumor heterogeneity, a focus on this topic from the practicing pathologist’ perspective is still pending.MethodsFour distant tumor areas of 40 organ-confined clear cell renal cell carcinomas were selected for histopathological and immunohistochemical evaluation. Tumor size, cell type (clear/granular), Fuhrman’s grade, Staging, as well as immunostaining with Snail, ZEB1, Twist, Vimentin, E-cadherin, β-catenin, PTEN, p-Akt, p110α, and SETD2, were analyzed for intratumor heterogeneity using a classification and regression tree algorithm.ResultsCell type and Fuhrman’s grade were heterogeneous in 12.5 and 60 % of the tumors, respectively. If cell type was homogeneous (clear cell) then the tumors were low-grade in 88.57 % of cases. Immunostaining heterogeneity was significant in the series and oscillated between 15 % for p110α and 80 % for Snail. When Snail immunostaining was homogeneous the tumor was histologically homogeneous in 100 % of cases. If Snail was heterogeneous, the tumor was heterogeneous in 75 % of the cases. Average tumor diameter was 4.3 cm. Tumors larger than 3.7 cm were heterogeneous for Vimentin immunostaining in 72.5 % of cases. Tumors displaying negative immunostaining for both ZEB1 and Twist were low grade in 100 % of the cases.ConclusionsIntratumor heterogeneity is a common event in clear cell renal cell carcinoma, which can be monitored by immunohistochemistry in routine practice. Snail seems to be particularly useful in the identification of intratumor heterogeneity. The suitability of current sampling protocols in renal cancer is discussed.

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Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

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Snail heterogeneity in clear cell renal cell carcinoma

et al. 2016

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“…Mathematical analysis of the data obtained has demonstrated that the most relevant parameters for predicting intratumor heterogeneity in CCRCC are tumor size, eosinophilic cellularity, Fuhrman grade, and the expression of Ki67 and COX2 (20). Neither CAIX nor BAP-1 have been found to be significantly associated with heterogeneity in this study (20), despite the two markers being directly involved in tumor aggressiveness (24,25).…”

Section: Immunohistochemical Heterogeneitymentioning

confidence: 92%

Intratumor heterogeneity in clear cell renal cell carcinoma: a review for the practicing pathologist

López

2016

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Intertumor heterogeneity, defined as the spectrum of morphological differences found in similar tumors in different patients, is a well-known event for pathologists. However, recent molecular studies have pointed to intratumor heterogeneity as one of the most important issues in human neoplasia in the next years. Clear cell renal cell carcinoma is an example of an intrinsically heterogeneous neoplasm, and some of the most salient advances in the knowledge of intratumor heterogeneity have been developed on it. This review intends to analyze this phenomenon in this tumor from the practicing pathologist's point of view. A careful study of the surgical specimen and an exhaustive tumor sampling are mandatory to keep relevant information. Currently accepted protocols designed for renal tumor sampling may be insufficient. As a result, a different approach to tumor sampling is advisable to ascertain that intratumor heterogeneity, if present, will be well represented in the selected material.

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“…Andere interessante prognostische Marker existieren im KNK, wie zum Beispiel Ki-67, ein Marker für den Proliferationsindex, BAP-1 und COX-2 [36]. Eine Überexpression dieser Proteine könnte ein Zeichen für ein schlechtes Überleben sein.…”

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Die Rolle von Biomarkern in Diagnose, Prognose und Therapie von Patienten unter immunonkologischer Therapie mit urologischen Malignomen

et al. 2018

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In recent years, fundamental research has yielded new insights into tumour biology, and new treatments have been developed. This review highlights the role of the pathologist and how he can support clinicians to find the right treatment for each patient. We explain the problems of the molecular subgroups of bladder cancer, the role of neo-adjuvant chemotherapy in the context of these findings, and show the important role of checkpoint inhibitors. Furthermore we focus on kidney cancer, with the clear cell carcinoma as the most frequent tumour type. We briefly consider prostate cancer, which as a hormone-dependent tumour probably requires different therapies. We also try to show the feasibility and the limits of pathology with the emerging tumour markers.

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Large (>3.8 cm) clear cell renal cell carcinomas are morphologically and immunohistochemically heterogeneous

Cited by 19 publications

References 35 publications

Snail heterogeneity in clear cell renal cell carcinoma

Snail heterogeneity in clear cell renal cell carcinoma

Intratumor heterogeneity in clear cell renal cell carcinoma: a review for the practicing pathologist

Die Rolle von Biomarkern in Diagnose, Prognose und Therapie von Patienten unter immunonkologischer Therapie mit urologischen Malignomen

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