scholarly journals Intra-tumour molecular heterogeneity of clear cell renal cell carcinoma reveals the diversity of the response to targeted therapies using patient-derived xenograft models

Oncotarget ◽  
2017 ◽  
Vol 8 (30) ◽  
pp. 49839-49850 ◽  
Author(s):  
Baoan Hong ◽  
Yong Yang ◽  
Sheng Guo ◽  
Shayiremu Duoerkun ◽  
Xiaohu Deng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Patient Derived Xenograft ◽  
Xenograft Models

scholarly journals Economic Burden of Metastatic Clear-Cell Renal Cell Carcinoma for French Patients Treated With Targeted Therapies

2019 ◽  
Vol 17 (1) ◽  
pp. e227-e234 ◽  
Author(s):  
Tiphaine Cholley ◽  
Antoine Thiery-Vuillemin ◽  
Samuel Limat ◽  
Marion Hugues ◽  
Fabien Calcagno ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Economic Burden ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

2013 ◽  
Vol 137 (4) ◽  
pp. 467-480 ◽  
Author(s):  
Rajen Goyal ◽  
Elizabeth Gersbach ◽  
Ximing J. Yang ◽  
Stephen M. Rohan
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumor ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Immunohistochemical Stains

Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. Data Sources.—Published literature and personal experience. Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.

Intratumoural heterogeneity may hinder precision medicine strategies in patients with clear cell renal cell carcinoma

2018 ◽  
Vol 71 (5) ◽  
pp. 467-471 ◽  
Author(s):  
Maria Rosaria Raspollini ◽  
Ilaria Montagnani ◽  
Rodolfo Montironi ◽  
Francesca Castiglione ◽  
Guido Martignoni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Precision Medicine ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Precision Oncology ◽  
Cell Renal Cell Carcinoma ◽  
Renal Sinus ◽  
The Moment

Clear cell renal cell carcinoma (ccRCC) is an heterogeneous tumour at architectural, cellular and molecular level, a reason why the 2014 International Society of Urological Pathology consensus recommended wide sampling of RCC masses to include at least 1 block/cm of tumour together with perpendicular sections of the tumour/perinephric fat interface and the tumour/renal sinus interface. Intratumoural molecular heterogeneity may be a limitation at the moment of defining precision medicine strategies based on gene mutation status. This study analyses the presence of any mutation of KRAS, NRAS, BRAF, PIK3CA, ALK, ERBB2, DDR2, MAP2K1, RET and EGFR genes in 20 tissue blocks from a case of ccRCC and its metastasis. We observed the presence of the mutation at pH1047R of PIK3CA gene in five samples of the tumour, while the remaining 15 samples did not show any mutation at PIK3CA or any other investigated gene. There is a great need to develop novel RCC sampling strategies to overcome tumour heterogeneity prior to define precision oncology strategies.

Dynamic contrast-enhanced MRI to predict intratumoral molecular heterogeneity in clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4580-4580
Author(s):  
Durga Udayakumar ◽  
Ze Zhang ◽  
Durgesh Dwivedi ◽  
Yin Xi ◽  
Tao Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Molecular Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Post Contrast ◽  
Dce Mri ◽  
Dynamic Contrast Enhanced ◽  
Contrast Enhanced

4580 Background: Mutation/inactivation of VHL in clear cell renal cell carcinoma (ccRCC) leads to upregulation of hypoxia inducible factors ( HIFs) and angiogenesis. However, ccRCC is characterized by high intra-tumor heterogeneity (ITH). Random small samples such as those in percutaneous biopsies are likely limited for characterization of molecular alterations in heterogeneous ccRCCs. We hypothesize that whole-tumor dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is useful to noninvasively identify ITH in ccRCC. Methods: This IRB-approved, prospective, HIPAA-compliant study, included 62 ccRCCs. 3T DCE MRI was obtained prior to nephrectomy. Surgical specimens were sectioned to match MRI acquisition plane. 182 snap frozen samples (49 tumors) and adjacent uninvolved renal parenchyma (URP) were collected. RNA isolations, cDNA library preparation and mRNA sequencing were performed using standard protocols. RNA expression in 81 tumor samples were correlated (Spearman ranked) with % enhancement in a region of interest (ROI) drawn in the same location of the tumor on pre- and 3 different post-contrast DCE MRI phases. Gene function overrepresentation (OR) analyses were done on top positively and negatively correlated genes. False discovery rate (FDR) < 0.1 was considered statistically significant. Results: Principal component analysis of > 20,000 genes indicated distinct gene expression in tumors from URP. Unsupervised clustering showed enrichment of ccA samples (better prognosis) compared to ccB samples (worse prognosis). Importantly, ccA and ccB samples coexisted in 25% of tumors. DCE-MRI % enhancement correlated with expression of > 300 genes (p < 0.003, FDR < 0.1). OR analyses placed angiogenic pathway gene processes and the immune/inflammatory response processes within the top 5 positively- and negatively-correlated gene functions, respectively. HIF2 target genes correlated positively with % enhancement. Conclusions: DCE MRI detects specific molecular signatures and may help overcome the challenges of ITH in ccRCC. Further research is needed to explore the potential role of DCE MRI to assess response to antiangiogenic and immune-based therapies.

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