Clear cell renal cell carcinoma with wild-type von Hippel-Lindau gene: a non-existent or new tumour entity?

2018 ◽  
Vol 74 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Aashil A Batavia ◽  
Peter Schraml ◽  
Holger Moch
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Wild Type ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Tumour Entity

scholarly journals Rho-associated kinase 1 inhibition is synthetically lethal with von Hippel-Lindau deficiency in clear cell renal cell carcinoma

Oncogene ◽  
2016 ◽  
Vol 36 (8) ◽  
pp. 1080-1089 ◽  
Author(s):  
J M Thompson ◽  
Q H Nguyen ◽  
M Singh ◽  
M W Pavesic ◽  
I Nesterenko ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Synthetically Lethal

scholarly journals Clear Cell Renal Cell Carcinoma Growth Correlates with Baseline Diffusion-weighted MRI in Von Hippel–Lindau Disease

Radiology ◽  
2020 ◽  
Vol 295 (3) ◽  
pp. E10-E10
Author(s):  
Faraz Farhadi ◽  
Moozhan Nikpanah ◽  
Anna K. Paschall ◽  
Ahmad Shafiei ◽  
Ashkan Tadayoni ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Diffusion Weighted Mri ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Diffusion Weighted ◽  
Von Hippel Lindau Disease

scholarly journals Targeting β2-Adrenergic Receptors Shows Therapeutical Benefits in Clear Cell Renal Cell Carcinoma from Von Hippel–Lindau Disease

2020 ◽  
Vol 9 (9) ◽  
pp. 2740
Author(s):  
Virginia Albiñana ◽  
Eunate Gallardo-Vara ◽  
Isabel de Rojas-P ◽  
Lucia Recio-Poveda ◽  
Tania Aguado ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau ◽  
Gene And Protein Expression ◽  
Ici 118,551

Von Hippel–Lindau (VHL), is a rare autosomal dominant inherited cancer in which the lack of VHL protein triggers the development of multisystemic tumors such us retinal hemangioblastomas (HB), CNS-HB, and clear cell renal cell carcinoma (ccRCC). ccRCC ranks third in terms of incidence and first in cause of death. Standard systemic therapies for VHL-ccRCC have shown limited response, with recurrent surgeries being the only effective treatment. Targeting of β2-adrenergic receptor (ADRB) has shown therapeutic antitumor benefits on VHL-retinal HB (clinical trial) and VHL-CNS HB (in vitro). Therefore, the in vitro and in vivo antitumor benefits of propranolol (ADRB-1,2 antagonist) and ICI-118,551 (ADRB-2 antagonist) on VHL−/− ccRCC primary cultures and 786-O tumor cell lines have been addressed. Propranolol and ICI-118,551 activated apoptosis inhibited gene and protein expression of HIF-2α, CAIX, and VEGF, and impaired partially the nuclear internalization of HIF-2α and NFĸB/p65. Moreover, propranolol and ICI-118,551 reduced tumor growth on two in vivo xenografts. Finally, ccRCC patients receiving propranolol as off-label treatment have shown a positive therapeutic response for two years on average. In summary, propranolol and ICI-118,551 have shown antitumor benefits in VHL-derived ccRCC, and since ccRCCs comprise 63% of the total RCCs, targeting ADRB2 becomes a promising drug for VHL and other non-VHL tumors.

Significance of PI3K signalling pathway in clear cell renal cell carcinoma in relation to VHL and HIF status

2020 ◽  
pp. jclinpath-2020-206693
Author(s):  
Raviprakash Tumkur Sitaram ◽  
Maréne Landström ◽  
Göran Roos ◽  
Börje Ljungberg
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumour Progression ◽  
Recent Decade ◽  
Signalling Pathway ◽  
Signalling Pathways ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau

Renal cell carcinoma (RCC) includes diverse tumour types characterised by various genetic abnormalities. The genetic changes, like mutations, deletions and epigenetic alterations, play a crucial role in the modification of signalling networks, tumour pathogenesis and prognosis. The most prevalent RCC type, clear cell RCC (ccRCC), is asymptomatic in the early stages and has a poorer prognosis compared with the papillary and the chromophobe types RCCs. Generally, ccRCC is refractory to chemotherapy and radiation therapy. Loss of von Hippel-Lindau (VHL) gene and upregulation of hypoxia-inducible factors (HIF), the signature of most sporadic ccRCC, promote multiple growth factors. Hence, VHL/HIF and a variety of pathways, including phosphatase and TEnsin homolog on chromosome 10/phosphatidylinositol-3-kinase (PI3K)/AKT, are closely connected and contribute to the ontogeny of ccRCC. In the recent decade, multiple targeting agents have been developed based on blocking major signalling pathways directly or indirectly involved in ccRCC tumour progression, metastasis, angiogenesis and survival. However, most of these drugs have limitations; either metastatic ccRCC develops resistance to these agents, or despite blocking receptors, tumour cells use alternate signalling pathways. This review compiles the state of knowledge about the PI3K/AKT signalling pathway confined to ccRCC and its cross-talks with VHL/HIF pathway.

scholarly journals Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma

2016 ◽  
Vol 14 (3) ◽  
pp. 2785-2790 ◽  
Author(s):  
Ziyi Zhao ◽  
Changjin Chen ◽  
Junzhi Lin ◽  
Wentong Zeng ◽  
Juan Zhao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau

scholarly journals Mutant versions of von Hippel-Lindau (VHL) can protect HIF1α from SART1-mediated degradation in clear-cell renal cell carcinoma

Oncogene ◽  
2015 ◽  
Vol 35 (5) ◽  
pp. 587-594 ◽  
Author(s):  
Á Ordóñez-Navadijo ◽  
E Fuertes-Yebra ◽  
B Acosta-Iborra ◽  
E Balsa ◽  
A Elorza ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Von Hippel Lindau

scholarly journals Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 123
Author(s):  
Francesca Giunchi ◽  
Tania Franceschini ◽  
Elisa Gruppioni ◽  
Annalisa Altimari ◽  
Elisa Capizzi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Mutational Analysis ◽  
Papillary Renal Cell Carcinoma ◽  
Tumor Type ◽  
Wild Type ◽  
Cell Renal Cell Carcinoma

Background: Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC). Methods: We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade. Results: All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting results. Among the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored VHL mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected VHL mutations; two (33%) harbored pathogenic mutations in the p53 or the CKIT genes; and one (16%) was wild type. Conclusion: We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least VHL mutations.

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