Prospective assessment of circulating endothelial cells (CECs) as early markers of clear cell renal cell carcinoma (CCRCC) progression in first line setting: The Circles study (SOGUG 2011-01).

TPS4685 Background: Since the identification of Von Hippel Lindau (VHL) gene mutations as a critical step in the development of most Clear Cell Renal Cell Carcinomas (CCRCC), neoangionesis inhibition has become a cornerstone in their treatment. Despite the proven efficacy of antiangiogenic drugs, most patients will not achieve partial response by RECIST criteria. Thus, to accurately determine tumor progression is a challenging question incompletely answered by traditional radiological assessment. In recent years CECs counts have been proposed as surrogate biomarkers of angiogenesis that could be used for monitoring tumor evolution while on targeted therapies. We aim to figure out if CECs elevations could anticipate radiological progression in CCRCC. Methods: An observational prospective study is being performed in 10 institutions members of the Spanish Oncology Genitourinary group (SOGUG). Patients older than 18 years with histologically proven CCRCC on first line treatment with any targeted drug who have not progressed after 3 months of therapy are considered elegible. Recruitment begun on August the 1st 2011 and 15 of the 75 scheduled patients have been included so far. CECs are periodically collected in peripheral blood every 6 weeks for 15 months or radiological tumor progression, whatever occurs first. Median CEC values will be calculated and stated by descriptive statistics (Cellsearch, VERIDEX). To explore the evolution of CECs counts along treatment a linear model will be constructed. An association among CECs counts changes and time to progression will be analyzed with Cox model.

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Prospective assessment of circulating endothelial cells (CECs) as early markers of clear cell renal cell carcinoma (CCRCC) progression in first-line setting: The Circles study (SOGUG 2011-01).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.436 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 436-436

Author(s):

Victor Oyarvides ◽

Daniel Castellano ◽

Luis Leon Mateos ◽

Emilio Esteban ◽

Laura Basterretxea ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Endothelial Cells ◽

Tumor Progression ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Circulating Endothelial Cells ◽

First Line ◽

Cell Renal Cell Carcinoma ◽

Significant Difference

436 Background: Angiogenesis inhibitors have become a cornerstone in the management of clear cell renal cell carcinoma (CCRCC). Since circulating endothelial cells (CECs) counts have been proposed as surrogate biomarkers of angiogenesis, they could potentially be used to assess the activity of such drugs. Methods: An observational prospective study is being performed in 11 institutions members of the SOGUG group. Patients with confirmed CCRCC on first-line treatment who have not progressed after 3 months of therapy are considered eligible. CECs (CD 105+,CD 45-, DAPI + cells assessed by the Cell Search system), are determined every 6 weeks for 15 months or radiological tumor progression. Results: Up to 64 of the 75 scheduled patients have already been recruited. Mean age was 64 years, 73% were men and 27% women. Distribution upon MSKCC risk cathegories was: good 30%, intermediate 58%, poor 3% and not available (N/A) 9%. 57 (90%) patients received sunitinib, 3 (5%) pazopanib, 1 (2%) temsirolimus and was N/A in 3 (5%). The CECs counts were determined in 60 patients. At baseline median was 47 cells/4 ml (range 4-480). When comparing patients who experienced tumor progression while on study (11 cases) with patients who did not (28 CECs/4 ml vs. 73 CECs/4ml respectively), a significant difference was found (p = 0.002, t-student). Several exploratory analysis regarding concomitant conditions and patients and tumor characteristics showed that cases with heavily treated hypertension (8 in 60 patients) had lower baseline CECs counts, though without statistical significance (p = 0.068, t-student). Conclusions: Our data point to a different behaviour of CECs counts among CCRCC patients tretated with anitangiogenic drugs that could lead to identify specific subpopulations. Mature results will be presented at the meeting.

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C137 VON HIPPEL-LINDAU GENE MUTATIONS IN PATIENTS WITH CLEAR CELL RENAL CELL CARCINOMA WITHIN THE POPULATION OF GREATER POLAND

European Urology Supplements ◽

10.1016/s1569-9056(13)60136-0 ◽

2012 ◽

Vol 11 (4) ◽

pp. 114

Author(s):

A. Ida ◽

E. Zodro ◽

J. Wesoly ◽

Z. Kwias

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Mutations ◽

Cell Renal Cell Carcinoma ◽

Von Hippel Lindau

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Von Hippel-Lindau Gene Mutations and Vascular Endothelial Growth Factor Immunoexpression in Clear Cell Renal Cell Carcinoma

Myanmar Health Sciences Research Journal ◽

10.34299/mhsrj.00943 ◽

2019 ◽

Vol 31 (2) ◽

pp. 170-175

Keyword(s):

Renal Cell Carcinoma ◽

Targeted Therapy ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Mutations ◽

Cell Renal Cell Carcinoma ◽

Vhl Gene ◽

Von Hippel Lindau ◽

Clear Cell Rcc

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults representing about 3% of all newly diagnosed cancers in the United States. Clear cell RCC is the most common subtype (70-80%) of RCC. Clear cell RCC can be familial, but 95% of cases are sporadic resulting from the germline or acquired mutation of Von Hippel-Lindau (VHL) gene. VHL tumor suppressor gene functions as a down regulator of vascular endothelial growth factor (VEGF). Mutations of VHL gene result in overexpression of VEGF, neoangiogenesis and tumor metastasis. Nowadays, anti-VEGF targeted therapy is used for treating metastasis clear cell RCC. However, drug resistance occurs over time. VHL gene targeted therapy combined with anti-VEGF therapy should be considered and detection of VHL gene mutations status becomes essential in these cases. The present study was aimed to detect the VHL gene mutations status and VEGF immunoexpression in 62 clear cell RCC patients by conventional polymerase chain reaction and immunohistochemistry. Three primer pairs were used to detect the mutations of 3 exons in VHL gene. The positive cases for VHL exon 1 mutation, exon 2 mutation and exon 3 mutation were checked by 2% agarose gel electrophoresis. Tumor grading was done by Fuhrman nuclear grading system and staging was done by pathologic TNM staging system. Fifty cases (80.65%) were VHL gene mutation positive and 12 cases (19.35%) were negative. VHL gene mutations were significantly associated with histological grades (p=0.005). Out of 62 cases, 24 cases were weakly positive (1+) and 38 cases were strongly positive (2+) VEGF immuno-reactivity. There was statistically significant association between VEGF immunoexpression and histological grades of clear cell renal cell carcinoma (p=0.00) as well as tumor stage (p=0.01). It was also found that VEGF immunoexpression of clear cell RCC was significantly associated with VHL gene mutation positive tumours (p=0.00). These results can be helpful in further invention of molecular targeted therapy for drug-resistant clear cell RCC patients.

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