Relationship between VHL mutation status, tumor VEGF expression and plasma VEGF measurement in sporadic renal cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4602-4602 ◽  
Author(s):  
P. Fergelot ◽  
N. Rioux-Leclercq ◽  
S. Zerrouki ◽  
K. Bensalah ◽  
J. Patard
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Vegf Expression ◽  
Fuhrman Grade ◽  
Mutation Status ◽  
Mutational Status

4602 Background: The relationship between VHL mutation status and prognosis in renal cell carcinoma (RCC) remains controversial. The aim of this study was to evaluate prospectively the association between VHL status, tumor VEGF expression, plasma VEGF levels and usual prognostic parameters in RCC. Methods: 70 patients with clear cell RCCs were included in this study. Genomic DNA was extracted using the QIAmp DNA mini kit (Qiagen) from frozen tumor samples. Four amplimers covering the whole coding sequence and exon/intron junctions of the VHL gene were synthetized by PCR followed by Big Dye sequencing (Applied Biosystems). Mutation bearing sequences were confirmed in a second round of PCR and sequencing reactions. Tumor VEGF expression was determined by immunohistochemistry and plasma VEGF was measured by enzyme-linked immunosorbent assay (Quantikine immunoassay, R&D systems). Results were expressed in pg/ml. Qualitative and quantitative variables were compared by using Chi-square (Fischer exact test) and Student t tests, respectively. Results: A VHL mutation was found in 46 cases (65.7%). VHL mutations were localized in exon 1, 2 and 3 in 23, 16 and 7 cases respectively. Median tumor VEGF expression was 45% (5–100). Median plasma VEGF was 104 pg/ml (13–1430). A significant association was found between VHL mutation and N stage (p: 0.01), Fuhrman grade, symptoms at presentation (p: 0.02) or tumor size (p: 0.007). A VHL mutation was found in 83.5% of low grade (G1–2) and 80% of incidental tumors respectively. A trend towards more frequent VHL mutations was observed in T1 tumors (87% mutation rate, p: 0.07) and in good performance status patients. Interestingly, VEGF tumor expression and plasma VEGF levels were not significantly different among patients with tumors having or not mutated VHL (p: 0.7). Conclusion: VHL mutations are more frequent in small incidental low stage or low grade tumors. Although VHL inactivation was not specifically determined in this study, we failed to show any association between VHL mutational status and VEGF tumor or plasma expression suggesting that other pathways than the VHL/HIF axis are required for explaining the angiogenic phenotype of RCC. No significant financial relationships to disclose.

373: Relationship Between VHL Mutation Status, Tumor VEGF Expression and Serum VEGF Measurement in Sporadic Renal Cell Carcinoma

2006 ◽  
Vol 175 (4S) ◽  
pp. 122-122
Author(s):  
Patricia Fergelot ◽  
Nathalie Rioux-Leclercq ◽  
Bernard Lobel ◽  
Francois Guille ◽  
Jean-Jacques Patard
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Vegf Expression ◽  
Mutation Status ◽  
Sporadic Renal Cell Carcinoma

Biological significance of serum VEGF measurement in renal cell carcinoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4596-4596
Author(s):  
J. Patard ◽  
N. Rioux-Leclercq ◽  
K. Bensalah ◽  
P. Fergelot
Keyword(s):  
Renal Cell Carcinoma ◽  
Platelet Count ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
Enzyme Linked Immunosorbent Assay ◽  
Alkaline Phosphatases ◽  
Fuhrman Grade ◽  
Histologic Subtype

4596 Background: VEGF plays an important role in Renal Cell Carcinoma (RCC) tumor angiogenesis and is a relevant molecular target. Our objective was to correlate serum VEGF measurement to clinical, biological and pathological variables in renal tumors. Methods: 206 patients who were operated for a renal tumor at our institution were prospectively assessed for serum VEGF measurement (enzyme-linked immunosorbent assay, R&D systems). Informed consent was obtained in all cases. Symptoms at presentation, pre-operative biology (haemoglobin, WBC count, platelet count, serum creatinin, calcemia, CRP, ASAT, ALAT, gamma-glutamyltransferase (γGT), Alkaline Phosphatases), TNM stage, Fuhrman grade and final pathology (benign vs malignant histology, histologic subtype) were systematically recorded. Qualitative and quantitative variables were compared by using Chi-square (Fischer exact test) and Student t tests, respectively. Results: There were 128 males (62.1%) and 78 females (37.9%). 185 tumors were malignant at histology (89.8%) including 155 tumors with clear cell histology (83.8%). Median serum VEGF level was 361 ng/ml (41–3090). Mean serum VEGF was not significantly different between benign and malignant tumors as well as between clear cell and non clear cell carcinomas (p: 0.4 and 0.8 respectively). Serum VEGF was strongly associated with symptoms, T Stage (p: 0.0001), N Stage (p: 0.004), Fuhrman grade (p: 0.007) and tumor necrosis (p: 0.004) but not with M Stage (p: 0.3). Serum VEGF was also found to be strongly associated with: haemoglobin, CRP, platelet count (p: 0.0001) and Alkaline phosphatases (p: 0.001). A weaker association was found between serum VEGF and γGT, ASAT (p: 0.05) or ALAT (p: 0.09). Finally serum VEGF was associated with cancer specific survival (p: 0.01). Conclusion: Serum VEGF is strongly associated with most usual clinical, biological and pathological prognostic parameters in RCC. Serum VEGF measurement should be further evaluated for prognostic purpose as well as for treatment monitoring. No significant financial relationships to disclose.

scholarly journals Differentiation of low and high grade renal cell carcinoma on routine MRI with an externally validated automatic machine learning algorithm

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Subhanik Purkayastha ◽  
Yijun Zhao ◽  
Jing Wu ◽  
Rong Hu ◽  
Aidan McGirr ◽  
...  
Keyword(s):  
Machine Learning ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clinical Decision Making ◽  
External Validation ◽  
Automatic Machine ◽  
Low Grade ◽  
High Grade ◽  
Fuhrman Grade

Abstract Pre-treatment determination of renal cell carcinoma aggressiveness may help guide clinical decision-making. We aimed to differentiate low-grade (Fuhrman I–II) from high-grade (Fuhrman III–IV) renal cell carcinoma using radiomics features extracted from routine MRI. 482 pathologically confirmed renal cell carcinoma lesions from 2008 to 2019 in a multicenter cohort were retrospectively identified. 439 lesions with information on Fuhrman grade from 4 institutions were divided into training and test sets with an 8:2 split for model development and internal validation. Another 43 lesions from a separate institution were set aside for independent external validation. The performance of TPOT (Tree-Based Pipeline Optimization Tool), an automatic machine learning pipeline optimizer, was compared to hand-optimized machine learning pipeline. The best-performing hand-optimized pipeline was a Bayesian classifier with Fischer Score feature selection, achieving an external validation ROC AUC of 0.59 (95% CI 0.49–0.68), accuracy of 0.77 (95% CI 0.68–0.84), sensitivity of 0.38 (95% CI 0.29–0.48), and specificity of 0.86 (95% CI 0.78–0.92). The best-performing TPOT pipeline achieved an external validation ROC AUC of 0.60 (95% CI 0.50–0.69), accuracy of 0.81 (95% CI 0.72–0.88), sensitivity of 0.12 (95% CI 0.14–0.30), and specificity of 0.97 (95% CI 0.87–0.97). Automated machine learning pipelines can perform equivalent to or better than hand-optimized pipeline on an external validation test non-invasively predicting Fuhrman grade of renal cell carcinoma using conventional MRI.

Renal biopsy cell cycle proliferation (CCP) score to predict adverse surgical pathology in renal cell carcinoma.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 747-747
Author(s):  
Jeffrey J. Tosoian ◽  
Adam S. Feldman ◽  
Madeline Abbott ◽  
Rohit Mehra ◽  
Placede Tiemeny ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Multivariable Analysis ◽  
Surgical Pathology ◽  
Patient Specific ◽  
Low Grade ◽  
Discriminative Performance ◽  
Fuhrman Grade

747 Background: The role of renal mass biopsy (RMB) in risk stratifying patients with renal cell carcinoma (RCC) is unclear. We sought to determine whether the cell cycle proliferation (CCP) score from RMB can improve risk stratification of localized RCC. Methods: We identified patients with RCC who underwent RMB and subsequent partial/radical nephrectomy from 2000-2014. We used multivariable logistic regression to determine the association of patient-level variables and biopsy CCP score with adverse surgical pathology (Fuhrman grade 3-4, pT stage≥3, papillary type II histology, or evidence of metastasis at surgery). Effect size was estimated with odds ratios (OR) and discriminative performance with AUC. Results: Overall, 94 of 202 patients (46%) had adverse surgical pathology. On multivariable analysis, CCP score >0 was associated with 2.38-fold increased odds of adverse pathology (Table). Relative to the model omitting CCP score (AUC=0.70), the addition of CCP score as a continuous (AUC=0.731) or binary (AUC=0.730) variable yielded increased discriminative performance. Similar associations were observed in an analysis limited to patients with low-grade tumors on biopsy (bCCP: OR 2.44, p=0.024; cCCP: OR 1.57, p=0.11). In both models, increased lesion size on imaging was consistently associated with adverse pathology. Conclusions: Among patients with RCC, biopsy CCP score >0 was independently associated with adverse pathology, suggesting this classifier provides prognostic information beyond conventional pathologic data. Biopsy CCP score could be used to better guide patient-specific management.[Table: see text]

215: Combining VHL Mutation Status, Tumor and Plasma VEGF Expression for Predicting Progression in Sporadic Clear Cell Renal Cell Carcinoma

2007 ◽  
Vol 177 (4S) ◽  
pp. 72-72
Author(s):  
Jean-Jacques Patard ◽  
Nathalie Rioux-Leclercq ◽  
Selim Zerrouki ◽  
Marc Denis ◽  
Patricia Fergelot
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Vegf Expression ◽  
Cell Renal Cell Carcinoma ◽  
Mutation Status

scholarly journals Small Renal Masses With Tumor Size 0 to 2 cm: A SEER-Based Study and Validation of NCCN Guidelines

2020 ◽  
Vol 18 (10) ◽  
pp. 1340-1347
Author(s):  
Angela Pecoraro ◽  
Giuseppe Rosiello ◽  
Stefano Luzzago ◽  
Marina Deuker ◽  
Franciska Stolzenbach ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Low Grade ◽  
Fuhrman Grade ◽  
Histologic Subtype ◽  
Renal Lesions ◽  
Synchronous Metastases ◽  
Histologic Subtypes

Background: The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce. Methods: Within the SEER database (2002–2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1–2 vs FG3–4), age category, and sex. In addition, rates of synchronous metastases were quantified. Results: Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1–2 clear cell histologic subtype (70.8%–50.3%) but higher rates of FG1–2 papillary (11.1%–23.9%) and chromophobe histologic subtypes (6.2%–8.5%). Overall, 14.5% individuals harbored FG3–4 clear cell (9.8%) or FG3–4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3–4 clear-cell and FG3–4 papillary histologic subtypes increased with age, more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3–4 papillary histologic subtype, respectively, except for 13.8% in the sarcomatoid dedifferentiation histologic subtype. Conclusions: Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3–4 minority. Even in patients with the FG3–4 histologic subtype, rates of synchronous metastases are virtually zero.

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma

2021 ◽  
pp. 107815522110055
Author(s):  
Ruggero Lasala ◽  
Fiorenzo Santoleri ◽  
Alessia Romagnoli ◽  
Felice Musicco ◽  
Paolo Abrate ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Relevant Literature ◽  
Real Life ◽  
Ecog Performance Status ◽  
Target Therapies ◽  
Baseline Characteristics

Introduction Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. Materials and Methods Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. Results We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS. Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

scholarly journals Identification of miR-20a-5p as Robust Normalizer for Urine microRNA Studies in Renal Cell Carcinoma and A Profile of Dysregulated microRNAs

2021 ◽  
Vol 22 (15) ◽  
pp. 7913
Author(s):  
Julia Oto ◽  
Raquel Herranz ◽  
Emma Plana ◽  
José Vicente Sánchez-González ◽  
Javier Pérez-Ardavín ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Diagnostic Value ◽  
Diagnostic Model ◽  
Low Grade ◽  
Non Invasive ◽  
Good Expression ◽  
Independent Cohort

Renal cell carcinoma (RCC) is the third most frequent urinary malignancy and one of the most lethal. Current diagnostic and follow-up techniques are harmful and unspecific in low-grade tumors. Novel minimally invasive markers such as urine microRNAs (miRNAs) are under study. However, discrepancies arise among studies in part due to lack of consent regarding normalization. We aimed to identify the best miRNA normalizer for RCC studies performed in urine samples together with a miRNA profile with diagnostic value and another for follow-up. We evaluated the performance of 120 candidate miRNAs in the urine of 16 RCC patients and 16 healthy controls by RT-qPCR followed by a stability analysis with RefFinder. In this screening stage, miR-20a-5p arose as the most stably expressed miRNA in RCC and controls, with a good expression level. Its stability was validated in an independent cohort of 51 RCC patients and 32 controls. Using miR-20a-5p as normalizer, we adjusted and validated a diagnostic model for RCC with three miRNAs (miR-200a-3p, miR-34a-5p and miR-365a-3p) (AUC = 0.65; Confidence Interval 95% [0.51, 0.79], p = 0.043). let-7d-5p and miR-205-5p were also upregulated in patients compared to controls. Comparing RCC samples before surgery and fourteen weeks after, we identified let-7d-5p, miR-152-3p, miR-30c-5p, miR-362-3p and miR-30e-3p as potential follow-up profile for RCC. We identified validated targets of most miRNAs in the renal cell carcinoma pathway. This is the first study that identifies a robust normalizer for urine RCC miRNA studies, miR-20a-5p, which may allow the comparison of future studies among laboratories. Once confirmed in a larger independent cohort, the miRNAs profiles identified may improve the non-invasive diagnosis and follow-up of RCC.

scholarly journals Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jazmine Arévalo ◽  
David Lorente ◽  
Enrique Trilla ◽  
María Teresa Salcedo ◽  
Juan Morote ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Independent Manner ◽  
Fuhrman Grade ◽  
Transcription 3 ◽  
Aggressive Subtype

AbstractClear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0.002; 95% CI 1.004–1.026) or the cytosol (p = 0.040; 95% CI 1.003–1.042), significantly correlate with patients’ survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.

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