Cell heterogeneity in clear cell renal cell carcinoma

López, José I.; Guarch, Rosa; Larrinaga, Gorka; Corominas-Cishek, Alexandra; Orozco, Roberto

doi:10.1111/apm.12073

Cited by 17 publications

(9 citation statements)

References 17 publications

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“…The most common histological type of RCC with rhabdoid change is clear cell RCC and up to 35% of Fuhrman grade 4 clear cell RCCs displays rhabdoid features [2][3][4][5][6][7]. Rhabdoid morphology can be seen in 9.8% of cases with clear cell RCC consisting of all grades [24]. One case of hereditary leiomyomatosis and RCC with sarcomatoid change and rhabdoid features has been described [25].…”

Section: Microscopic Findingsmentioning

confidence: 99%

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

Karashima¹,

Inoue²,

Kasajima³

et al. 2015

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Section: Microscopic Findingsmentioning

confidence: 99%

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

Karashima¹,

Inoue²,

Kasajima³

et al. 2015

pjp

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“…Focal sarcomatoid cell change was found in one case. Rhabdoid and syncytial cells [14] were not detected. Grade heterogeneity was detected in 20 cases of the series (42 %) and always included high grade areas (grades 3 or 4) (Fig.…”

Section: Resultsmentioning

confidence: 89%

“…Recent studies, however, have demonstrated that more extensive tumour sampling of CCRCC yields data significantly different in terms of tumour grade and tumour cellularity in comparison to conventional sampling [13,14]. For instance, in a recent study, 28 CCRCCs were fully sampled and 17 tumour heterogeneities were found in terms of the presence of high grade areas while conventional sampling of the same tumours did show heterogeneity in 17 cases but high grade areas only in seven [13].…”

Section: Discussionmentioning

confidence: 95%

“…Pathologists have known for a long time that CCRCC is frequently microscopically heterogeneous, but studies trying to quantify this issue are rare [12][13][14]. Clinical and molecular data [12][13][14][15] suggest that conventional sampling of kidney tumours [16] probably allows only a partial and insufficient perception of tumour histology. In this context, minor foci of high grade as well as tumour areas with different genetic/epigenetic alterations [17] with impact on tumour behaviour could eventually be missed in some cases.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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Heterogeneity is an inherent event to tumour development that is lately receiving much attention in oncologic research. The topic is being addressed primarily at the molecular level, and results are promising. However, translation to practical medicine is still pending. Our intention in this study is to approach the problem in a series of clear cell renal cell carcinomas with the tools that pathologists use in routine practice. Three randomly selected areas of 48 clear cell renal cell carcinomas prospectively collected in two different institutions were analysed for intratumour heterogeneity. The evaluated parameters were tumour size, cell type (clear vs. eosinophilic), Fuhrman's grade and immunohistochemical expression of carbonic anhydrase IX, BRCA1-associated protein-1 (BAP-1), cyclooxygenase-2 (COX-2) and Ki67. Intratumour heterogeneity was detected in 26 cases (54 %). Cell type, grade and Ki67 index were the parameters more frequently heterogeneous amounting, respectively, 44, 42 and 38 %. Tumour size was a significantly discriminative factor to predict tumour heterogeneity, with a cut-off of 3.8 cm (p < 0.001). Aside from tumour size, the most relevant parameters related with intratumour heterogeneity were cell type (clear vs. eosinophilic), Fuhrman's grade and Ki67 and COX-2 expression patterns. Carbonic anhydrase 9 and BAP-1 did not show statistical relevance. We conclude that heterogeneity is a common event in clear cell renal cell carcinomas that may be overlooked in cases insufficiently sampled. Tumour size appears as a reliable tool in identifying this situation since clear cell renal cell carcinomas under 3.8 cm in diameter are always homogeneous. This point may help the pathologist to make decisions in tumour sampling.

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“…Previous studies on total samplings assays performed in two short series have shown very concerning data 11, 12 that are not acceptable in modern clinical practice. Being aware of the limitations provided by current protocols in unveiling ITH, both clinicians involved in patient treatment and basic researchers are appealing for urgent solutions 25 .…”

Section: The Problemmentioning

confidence: 96%

A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma

López

Cortés

2016

F1000Res

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Intratumor heterogeneity (ITH) is an inherent process in cancer development which follows for most of the cases a branched pattern of evolution, with different cell clones evolving independently in space and time across different areas of the same tumor. The determination of ITH (in both spatial and temporal domains) is nowadays critical to enhance patient treatment and prognosis. Clear cell renal cell carcinoma (CCRCC) provides a good example of ITH. Sometimes the tumor is too big to be totally analyzed for ITH detection and pathologists decide which parts must be sampled for the analysis. For such a purpose, pathologists follow internationally accepted protocols. In light of the latest findings, however, current sampling protocols seem to be insufficient for detecting ITH with significant reliability. The arrival of new targeted therapies, some of them providing promising alternatives to improve patient survival, pushes the pathologist to obtain a truly representative sampling of tumor diversity in routine practice. How large this sampling must be and how this must be performed are unanswered questions so far. Here we present a very simple method for tumor sampling that enhances ITH detection without increasing costs. This method follows a divide-and-conquer (DAC) strategy, that is, rather than sampling a small number of large-size tumor-pieces as the routine protocol (RP) advises, we suggest sampling many small-size pieces along the tumor. We performed a computational modeling approach to show that the usefulness of the DAC strategy is twofold: first, we show that DAC outperforms RP with similar laboratory costs, and second, DAC is capable of performing similar to total tumor sampling (TTS) but, very remarkably, at a much lower cost. We thus provide new light to push forward a shift in the paradigm about how pathologists should sample tumors for achieving efficient ITH detection.

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Cell heterogeneity in clear cell renal cell carcinoma

Cited by 17 publications

References 17 publications

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

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

A divide-and-conquer strategy in tumor sampling enhances detection of intratumor heterogeneity in routine pathology: A modeling approach in clear cell renal cell carcinoma

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