Cd70: A New Tumor Specific Biomarker for Renal Cell Carcinoma

Junker, Kerstin; Hindermann, Winfried; Eggeling, Ferdinand von; Diegmann, Julia; Haessler, Kirstin; Schubert, Jöerg

doi:10.1097/01.ju.0000158121.49085.ba

Cited by 75 publications

(47 citation statements)

References 16 publications

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“…Our studies showed a high-level expression of CD70 on RCC cells that might be expected to induce a strong immune response against the tumour. Frequent expression of CD70 on RCC was recently also reported by Junker et al (2005). Although RCC is known to be a highly immunogenic tumour, it is also a very aggressive cancer that is clearly able to escape immune surveillance.…”

Section: Discussionmentioning

confidence: 62%

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

Pj¹,

Ja²,

Steers

et al. 2006

Br J Cancer

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In order to identify potential markers of renal cancer, the plasma membrane protein content of renal cell carcinoma (RCC)-derived cell lines was annotated using a proteomics process. One unusual protein identified at high levels in A498 and 786-O cells was CD70 (TNFSF7), a type II transmembrane receptor normally expressed on a subset of B, T and NK cells, where it plays a costimulatory role in immune cell activation. Immunohistochemical analysis of CD70 expression in multiple carcinoma types demonstrated strong CD70 staining in RCC tissues. Metastatic tissues from eight of 11 patients with clear cell RCC were positive for CD70 expression. Immunocytochemical analysis demonstrated that binding of an anti-CD70 antibody to CD70 endogenously expressed on the surface of A498 and 786-O cell lines resulted in the rapid internalisation of the antibody -receptor complex. Coincubation of the internalising anti-CD70 antibody with a saporin-conjugated secondary antibody before addition to A498 cells resulted in 50% cell killing. These data indicate that CD70 represents a potential target antigen for toxin-conjugated therapeutic antibody treatment of RCC.

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Section: Discussionmentioning

confidence: 62%

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

Pj¹,

Ja²,

Steers

et al. 2006

Br J Cancer

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“…CD5 can focally be expressed in type B3 thymoma, urothelial carcinoma, malignant mesothelioma, and adenocarcinoma of various organs; 33 CD70 may be positive in renal cell carcinoma, nasopharyngeal carcinoma, and Hodgkin lymphoma. 34 Clear cell carcinoma of the thymus is exceedingly rare; [35][36][37][38] we have only seen two cases in our database of B120 thymic carcinomas. In addition to renal clear cell carcinomas, metastatic germ cell tumors (particularly seminoma), large B cell lymphoma, clear cell sarcoma or melanoma, and clear cell paraganglioma should be considered in the differential diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Extrathoracic metastases of thymic origin: a review of 35 cases

et al. 2012

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Thymic tumors are categorized as types A, AB, B1, B2, B3, and thymic carcinoma under the World Health Organization (WHO) classification. Thymomas are typically slow growing tumors that predominantly involve the surrounding structures through direct invasion, while thymic carcinomas tend to be more aggressive. A significant number of patients are asymptomatic and can present with metastases as the first presentation. The exact incidence of extrathoracic metastases from thymoma is not known. This study describes a series of 35 cases of histologically documented metastatic thymomas and thymic carcinomas at extrathoracic sites. These cases were classified according to the current World Health Organization (WHO) classification criteria, and we present their clinical data as well as discuss the differential diagnoses of these lesions. Our study shows that all types of thymic tumors, regardless of histologic type, can be associated with invasion and metastases to thoracic and extrathoracic sites. It is the most aggressive variant invading surrounding structures with metastases, 2 although embolic metastases of thymic carcinoma leading to extrathoracic metastases are very rare. 4 Since, thymic cancers invade locally, diagnoses of metastases are difficult. Locally advanced thymic tumors often present as pleural plaques, which can be misdiagnosed as lung metastases on imaging studies. Thus, it becomes very important to appropriately define metastases in these tumors. For this reason, we defined only lesions outside the thorax that were histologically similar to the primary thymic tumors as metastases.Although the exact incidence of extrathoracic metastases from thymoma is not known, in 1983, Ichino et al 5 documented 83 cases in the literature. However, most of the metastatic sites were not biopsied and histology was not available. In addition, the older literature does not make a distinction between epithelial lesions (true thymic tumors) and other neoplasms arising in the region of thymus. In any event, these studies suggest liver, bone, and lymph nodes as common sites of extrathoracic metastases of malignant thymoma. [4][5][6] Moreover,

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“…Altered CD70 expression was found in hematologic malignancies and also in solid tumors, such as nasopharyngeal carcinoma, thymic carcinoma, and brain tumors (9). The most frequent expression was reported in RCC (10)(11)(12)(13), but the mechanism that leads to the upregulation of CD70 in this tumor type is still unclear. Interestingly, CD70 expression is less prevalent in VHL unrelated RCC subtypes.…”

Section: Introductionmentioning

confidence: 99%

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

Ruf

Mittmann

Nowicka

et al. 2015

Clinical Cancer Research

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Purpose: CD70, a member of the TNF ligand superfamily, has been shown frequently overexpressed in clear cell renal cell carcinoma (ccRCC). The mechanisms of CD70's upregulation and its role in ccRCC are unknown.Experimental Design: CD70 expression was immunohistochemically analyzed in 667 RCCs and RCC metastases. Von Hippel-Lindau gene (VHL) mutations, expression patterns of VHL protein (pVHL), hypoxia-inducible factor (HIF) a, and several HIF targets were studied in tissues and cell lines and correlated with CD70 overexpression. Gene promoter analysis was performed to confirm CD70 as HIF target gene. Consecutive tissue sections were immunostained to reveal the relation between CD70-expressing RCCs and tumor-infiltrating lymphocytes positive for the CD70 receptor (CD27). CD70-mediated release of soluble CD27 in RCC was assessed by coculture experiments and sera analysis of patients with RCC.

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Cd70: A New Tumor Specific Biomarker for Renal Cell Carcinoma

Cited by 75 publications

References 16 publications

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

CD70 (TNFSF7) is expressed at high prevalence in renal cell carcinomas and is rapidly internalised on antibody binding

Extrathoracic metastases of thymic origin: a review of 35 cases

pVHL/HIF-Regulated CD70 Expression Is Associated with Infiltration of CD27+ Lymphocytes and Increased Serum Levels of Soluble CD27 in Clear Cell Renal Cell Carcinoma

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