Publications (25)83.23 Total impact
-
Article: Prognostic value of CXCR4 expression in patients with clear cell renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: Introduction: The expression of CXCR4 is implicated in the metastatic dissemination of different cancers. The information on its prognostic value has been very limited in clear cell renal cell carcinoma (ccRCC). Our objective was to explore the prognostic value of CXCR4 in ccRCC. Materials and methods: 104 patients with a ccRCC were studied. There were 69 men and 35 women with an average age of 64.5 years old (range: 34-86 years). The CXCR4 expression was evaluated by immunohistochemistry. The follow-up varied from 12 to 184 months with a mean of 79.5 months. Kaplan-Meier with a log rank test was performed to compare overall survival and cancer-specific survival after surgery. Univariate and multivariate analyses were performed according to the Cox regression model. Results: CXCR4 expression was found in 68/104 (65.4%) of tumor samples. CXCR4 expression was located in the nucleus in 55/68 (80.8%) cases while cytoplasm or membrane location was found in 13/68 (19.2%) cases. High expression was found in 25/68 (36.8%) cases. During follow-up, 39 patients died, of which 26 died of cancer. Kaplan-Meier analysis revealed that a high expression of CXCR4 was associated with a reduced overall survival (p=0.017) and cancer-specific survival (p=0.022). Univariate analysis indicated that a high expression of CXCR4 was a significant factor for a poorer overall survival (p=0.020) and cancer-specific survival (p=0.027). By multivariate analysis, a high expression of CXCR4 appeared to be an independent factor of overall survival (p=0.024) and cancer-specific survival (p=0.028). Conclusion: This study suggested that a high CXCR4 expression was correlated with a worse outcome for ccRCC patients.Histology and histopathology 04/2013; · 2.48 Impact Factor -
Article: Prognostic Value of Serum CA9 in Patients with Metastatic Clear Cell Renal Cell Carcinoma under Targeted Therapy.
[show abstract] [hide abstract]
ABSTRACT: Aim: Carbonic anhydrase 9 (CA9) has been found to be one of most powerful biomarkers for clear-cell renal cell carcinoma (RCC). The serum CA9 is detectable. The aim of this study was to evaluate the potential prognostic role of serum CA9 in patients with metastatic clear-cell RCC patients under targeted therapy. Serum samples came from the randomized phase 2 TORAVA trial. All patients received a targeted therapy (arm A designed as experimental group: temsirolimus and bevacizumab combination; arm B: sunitinib; arm C: interferon-alfa and bevacizumab). Seventy cases of metastatic clear-cell RCC were analyzed. There were 49 males and 21 females. The age ranged from 33.5 to 79.1 years with a median of 61.2 years. Serum samples were collected before treatment. Serum CA9 was quantified by enzyme-linked immunosorbent assay (ELISA). The correlation of the serum CA9 levels with the clinical parameters, treatment response and overall survival was analyzed. Overall survival estimates were calculated using the Kaplan-Meier method and compared by the log-rank test. Serum concentrations of CA9 ranged between 0 and 897.3 pg/ml, with an average of 94.4±176.6 pg/ml. There was no association between serum CA9 and clinical parameters such as Eastern Cooperative Oncology Group (ECOG) Performance Status (p=0.367) or Motzer classification (p=0.431). The serum CA9 levels were lower in the response group (64.7±104.7 pg/ml) than the no-response group (108.2±203.8 pg/ml), but the difference was not statisticlly significant (p=0.366). For the patient group overall, the Kaplan-Meier survival curve showed that high serum CA9 levels were significantly associated with shorter overall survival (hazard ratio=2.65, 95% confidence interval=1.19-5.92, log-rank test p=0.0136). For the major group of patients treated with temsirolimus and bevacizumab, the Kaplan-Meier survival curve showed that high serum CA9 levels were significantly associated with shorter overall survival (p=0.0006). Serum CA9 levels may be of clinical interest to predict the outcome for patients under targeted therapy for metastatic clear-cell RCC. CA9 may be used to select patients with metastatic clear cell RCC for clinical trials.Anticancer research 12/2012; 32(12):5447-51. · 1.73 Impact Factor -
Article: Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: OBJECTIVE: Our objective was to evaluate the levels of miR-210 in tumor and serum samples of conventional renal cell cancer (cRCC) patients to explore whether circulating miR-210 in serum can be used as a biomarker for the detection of cRCC. METHODS: The paired samples from primary cRCC tumors and adjacent non-tumoral renal parenchyma were collected from 32 patients with cRCC. Serum samples were obtained from 68 patients with a cRCC before surgery, 10 samples after one week of surgery, and 42 healthy individuals were included in this study. Real-time PCR was used to measure the microRNA level. The expression of miRNAs was normalized using the dCT method. Expression levels of miR-210 were compared using the Mann-Whitney U test or Wilcoxon test. Diagnostic performance of serum miR-210 level was calculated by using the receiver operating characteristic (ROC) curve. RESULTS: The average miR-210 level was higher in primary cRCC tissues than in normal tissue (p=0.004). For serum samples, the average level of miR-210 was significantly higher in cRCC patients than in controls (p<0.001). The serum miR-210 level yielded an AUC (the areas under the ROC curve) of 0.874 with a sensitivity of 81.0% and a specificity of 79.4%. Furthermore, the average serum level of miR-210 was significantly decreased in the patients one week after the operation (p=0.001). CONCLUSION: Serum mi-210 may have a potential as a novel noninvasive biomarker for the detection of cRCC.Experimental and Molecular Pathology 10/2012; · 2.42 Impact Factor -
Article: Combination of core biopsy and fine-needle aspiration increases diagnostic rate for small solid renal tumors.
[show abstract] [hide abstract]
ABSTRACT: Our aim was to evaluate the performance of combination of fine-needle aspiration (FNA) and core biopsy (CB) as a method for the diagnosis of small solid renal tumors. Ninety patients with a radiologically detected small solid renal tumor (≤ 4 cm) underwent a biopsy. Patient underwent FNA (FNA group, n=32) or CB (CB group, n=30) or combination of both FNA and CB (combination group, n=28). The diagnostic rate and accuracy of both techniques were assessed. The diagnostic rate of the combination group (92.9%) was superior to that of the FNA group (62.5%) and CB group (76.7%) (p=0.006, and p=0.147, respectively). In the combination group, 11 CBs were diagnostic with 13 nondiagnostic FNAs, while 4 FNAs were diagnostic with 6 nondiagnostic CBs. For tumors ≤ 2 cm, the combination of FNA and CB significantly increased the diagnostic rate, compared with FNA alone (p=0.033) and CB alone (p=0.044). The accuracy for FNA, CB and the combination of FNA and CB was 88%, 100% and 100%, respectively. The combination of FNA and CB increased the diagnostic rate of renal biopsy for the small solid renal tumors.Anticancer research 08/2012; 32(8):3463-6. · 1.73 Impact Factor -
Article: Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment.
[show abstract] [hide abstract]
ABSTRACT: Carbonic anhydrase 9 (CA9) is a transmembrane member of the carbonic anhydrase family. It catalyses the reversible hydration of carbon dioxide into bicarbonate and a proton, thus enabling tumour cells to maintain a neutral pH despite an acidic microenvironment. CA9 is not expressed in healthy renal tissue but is expressed in most clear cell renal cell carcinomas (CCRCC) through HIF-1α accumulation driven by hypoxia and inactivation of the VHL gene. CA9 expression can be detected in the tumour by immunohistochemistry (IHC), in blood and tissue by ELISA assay and RT-PCR. It has a 100% diagnostic specificity in solid renal tumours, while ELISA assays on aspiration fluids may help in atypical cysts. Blood-based assays, ELISA for CA9 antigen and RT-PCR for CA9 mRNA are promising for the prognosis and follow-up of localised CCRCC. In metastatic disease, high CA9 expression by IHC was reported to be a powerful prognostic marker with better survival and sensitivity to IL-2, but this is still debated. Almost no data are currently available on the association of CA9 expression and outcome to targeted drugs. The prognostic value of CA9 in CCRCC could be explained by the frequent VHL gene inactivation driving an early activation of the HIF pathway. The poorer prognosis associated with low CA9 expressing tumours could be due to the simultaneous overexpression of EGFR contributing to the activation of AkT and mTOR pathways. Targeting CA9 by inhibitors, radioimmunotherapy, monoclonal antibodies or vaccination is promising and offers new avenues for clinical research.European journal of cancer (Oxford, England: 1990) 12/2010; 46(18):3141-8. · 4.12 Impact Factor -
Article: CA9 as a molecular marker for differential diagnosis of cystic renal tumors.
[show abstract] [hide abstract]
ABSTRACT: CA9 is proven to be a powerful marker for clear cell renal cell carcinoma. The studies on CA9 have been limited to solid renal cell carcinomas (RCC). We have conducted a study of CA9 expression in renal cystic tumors. The purpose of the present study was to extend the utility of CA9 for cystic renal tumors. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to detect CA9 expression in cystic renal tumors. Forty-three cystic renal tumors (22 benign and 21 malignant) were included for the immunohistochemical staining. Thirty-six patients with a cystic renal mass (20 malignant and 16 benign cystic tumors) were studied to measure CA9 level in the fluid by ELISA. Sixteen cysts (9 malignant and 7 benign cysts) were subjected both to immunohistochemistry and CA9 measurement in the fluid. Using immunohistochemical staining, all the benign cystic renal tumors including the 18 simple cyst and 4 benign multilocular cystic nephromas did not express CA9. All 13 cystic clear cell RCC were scored as strong staining for CA9. For 8 multilocular clear cell RCC, 7 were scored as strong staining for CA9 and the other one was negative. There was a significant difference in positive percentage (P < 0.001) between the 2 groups of malignant and benign cysts. For the 16 benign cysts, the mean concentration of CA9 in the fluid of cyst was 162 ± 133 pg/ml (median: 0 pg/ml; range: 0-2140 pg/ml). For the 20 malignant renal cystic tumors, the mean concentration of CA9 in the fluid of cyst was 2043 ± 62 pg/ml (median: 2,140 pg/ml; range: 1,112-2,140 pg/ml). There was a significant difference in mean concentration of CA9 between the two groups of malignant and benign cysts (P < 0.001). The presence or absence of CA9 expression measured by immunohistochemistry and ELISA test was concordant in 14 out of 16 cases (88%). Malignant cystic renal tumors expressed strongly CA9 while the benign renal cysts did not express CA9. CA9 can be detected in the fluid of malignant cystic renal tumors. CA9 is a promising molecular marker to differentiate the malignant cystic renal tumors from the benign cysts.Urologic Oncology 09/2010; 30(4):463-8. · 3.22 Impact Factor -
Article: CA9 level in renal cyst fluid: a possible molecular diagnosis of malignant tumours.
[show abstract] [hide abstract]
ABSTRACT: The preoperative differentiation of malignant renal cystic tumours from benign lesions is critical, and it remains a common diagnostic problem. The aim was to examine if the Carbonic anhydrase 9 (CA9) level in cyst fluid can provide a molecular diagnosis of malignant cyst. Twenty-eight patients with a cystic renal mass were included. Fine-needle aspiration was performed to obtain the fluid. Postoperative pathology confirmed that there were 16 cystic renal cell carcinomas. Twelve benign cystic tumours were used as controls. One hundred microlitres of supernatant of cyst fluid was used to measure the CA9 protein level, which was measured by an enzyme-linked immunosorbent assay technique. CA9 was strongly detected and considered as positive in the cyst fluid of all 16 cystic malignant tumours (>1000 pg/ml), whereas its expression was negative in 11/12 benign cystic tumours (<300 pg/ml). The difference in percentages of positive CA9 between malignant and benign renal cystic tumours was significant (P < 0.001). The fluid of malignant cystic renal tumours contains a high level of CA9 protein. The measurement of CA9 level in cyst fluid may be used as a molecular diagnosis for differentiation between malignant and benign renal cystic masses.Histopathology 05/2009; 54(7):880-4. · 3.08 Impact Factor -
Article: Tissue compartment analysis for biomarker discovery by gene expression profiling.
[show abstract] [hide abstract]
ABSTRACT: Although high throughput technologies for gene profiling are reliable tools, sample/tissue heterogeneity limits their outcomes when applied to identify molecular markers. Indeed, inter-sample differences in cell composition contribute to scatter the data, preventing detection of small but relevant changes in gene expression level. To date, attempts to circumvent this difficulty were based on isolation of the different cell structures constituting biological samples. As an alternate approach, we developed a tissue compartment analysis (TCA) method to assess the cell composition of tissue samples, and applied it to standardize data and to identify biomarkers. TCA is based on the comparison of mRNA expression levels of specific markers of the different constitutive structures in pure isolated structures, on the one hand, and in the whole sample on the other. TCA method was here developed with human kidney samples, as an example of highly heterogeneous organ. It was validated by comparison of the data with those obtained by histo-morphometry. TCA demonstrated the extreme variety of composition of kidney samples, with abundance of specific structures varying from 5 to 95% of the whole sample. TCA permitted to accurately standardize gene expression level amongst >100 kidney biopsies, and to identify otherwise imperceptible molecular disease markers. Because TCA does not require specific preparation of sample, it can be applied to all existing tissue or cDNA libraries or to published data sets, inasmuch specific operational compartments markers are available. In human, where the small size of tissue samples collected in clinical practice accounts for high structural diversity, TCA is well suited for the identification of molecular markers of diseases, and the follow up of identified markers in single patients for diagnosis/prognosis and evaluation of therapy efficiency. In laboratory animals, TCA will interestingly be applied to central nervous system where tissue heterogeneity is a limiting factor.PLoS ONE 01/2009; 4(11):e7779. · 4.09 Impact Factor -
Article: Serum carbonic anhydrase 9 level is associated with postoperative recurrence of conventional renal cell cancer.
[show abstract] [hide abstract]
ABSTRACT: We explored the clinical usefulness of serum carbonic anhydrase 9 as a potential biomarker for conventional renal cell cancer. This study included 91 patients with conventional renal cell cancer and 32 healthy individuals. Enzyme linked immunosorbent assay was used to measure the carbonic anhydrase 9 level. A followup (median 38 months) was performed to track early recurrence after surgery for patients with localized disease. Recurrence-free survival curves were calculated by the Kaplan-Meier method and compared using the log rank test. The mean serum carbonic anhydrase 9 level in patients with metastatic conventional renal cell cancer (216.68 +/- 67.02 pg/ml) or localized conventional renal cell cancer (91.65 +/- 13.29 pg/ml) was significantly higher than in healthy individuals (14.59 +/- 6.22 pg/ml, p <0.001 and p = 0.001, respectively). The mean serum carbonic anhydrase 9 level in patients with metastatic conventional renal cell cancer was significantly higher than in those with localized disease (p = 0.004). Of patients with localized disease those with recurrence had a significantly higher serum carbonic anhydrase 9 than those without recurrence (p = 0.001). On univariate analysis serum carbonic anhydrase 9, tumor stage, tumor grade and tumor size were associated with recurrence. The recurrence-free survival curve indicates that patients with a high serum carbonic anhydrase 9 level had a significantly higher recurrence rate than those with a low serum carbonic anhydrase 9 (p = 0.001). Our data suggest that serum carbonic anhydrase 9 is increased as the tumor progression occurs. A high carbonic anhydrase 9 level is associated with postoperative recurrence.The Journal of urology 08/2008; 180(2):510-3; discussion 513-4. · 4.02 Impact Factor -
Article: Differential expression of prognostic markers in histological subtypes of papillary renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: To assess the expression of the tumour markers stromelysin 3, MUC1, p53 and cytokeratin-7 in papillary renal cell carcinoma (pRCC, for which two histological subtypes are distinguished, i.e. type 1 and type 2, the latter appearing to be associated with a poorer prognosis) and to determine whether any of these markers might be of prognostic value. In a retrospective study of 50 patients, the type and nuclear grade of tumours was determined by histological analyses, the presence of microvascular emboli detected, and the markers assessed by immunohistochemical analysis using anti-stromelysin 3, anti-MUC1, anti-p53 and anti-cytokeratin-7 antibodies. Twenty-five patients each had a type 1 or type 2 tumour. MUC1 and cytokeratin-7 were principally expressed in type 1 tumours, being detected in 76% and 84%, respectively. By contrast, p53 accumulated principally in type 2 tumours (36%); the accumulation of p53 was also associated with poorer survival. In patients with type 2 tumours with a more unfavourable development, stromelysin-3 expression was associated with a more advanced stage and a higher risk of metastases. Subtyping pRCC according to the recommended morphological criteria appears to be worthwhile, and can be reinforced by immunohistochemical tests capable of detecting cytokeratin-7 and MUC1 expression. Immunohistochemical detection of p53 is of prognostic value, as accumulation of this factor is associated with poorer survival.BJU International 08/2008; 102(2):183-7. · 2.84 Impact Factor -
Article: MN/CA9 as a novel molecular marker for the detection of cancer.
[show abstract] [hide abstract]
ABSTRACT: A major challenge in cancer detection is the limited sensitivity of techniques for the initial diagnosis and subsequent monitoring of tumour evolution. Recently, many studies have focused on the discovery of molecular markers for cancer diagnosis and prognosis. One promising molecular marker for cancer detection is MN/CA9. MN/CA9 is expressed in cancers of the kidney, breast, cervix, uterus, ovary, lung, oesophagus, stomach, colon, liver, pancreas, head and neck, bladder and skin, whereas its expression in normal tissues is limited to the gastrointestinal tract, gallbladder and pancreatic ducts. MN/CA9 can be detected in cytological samples, as well as in bodily fluids, to aid in cancer diagnosis. The usefulness of MN/CA9 is also demonstrated for the detection of distant metastasis after surgery. As molecular techniques become routinely available, MN/CA9 is a powerful molecular marker in cancer diagnosis and prognosis.Expert Opinion on Medical Diagnostics 09/2007; 1(1):91-97. -
Article: CA9 gene expression in conventional renal cell carcinoma: a potential marker for prediction of early metastasis after nephrectomy.
[show abstract] [hide abstract]
ABSTRACT: About 30-40% of patients with renal cell carcinoma (RCC) will develop metastasis after curative nephrectomy. There is a strong need to identify the early metastasis with conventional and molecular risk factors. The present study aimed to test if analysis of the CA9 gene can provide useful information to predict early metastasis after nephrectomy. This study included 63 patients with a conventional RCC. Ten tumors were N+ or/and M+ at diagnosis. The mean follow-up was 43 months (range, 4-67 months). About 11 M0N0 patients were found to have a metastasis during the follow-up. Quantitative RT-PCR of CA9 gene expression was performed. The metastasis-free survival curve was established according to the Kaplan-Meier method with comparison by the Log-Rank test. At diagnosis, the average of CA9 gene expression was significantly lower (p = 0.004) in metastatic tumors (N+ or/and M+) than in non-metastatic tumors (N0M0). For the follow-up of M0N0 patients, the metastasis-free survival rate was significantly higher (p = 0.005) in the high CA9 group than in the low-CA9 group. When combined with CA9, the metastasis-free survival rates, in terms of stage (p = 0.015) or grade (p = 0.010) were significantly different. When the stage, grade, and CA9 were combined, there was a significant difference (p = 0.004) in metastasis-free survival rates (T1T2 + G1G2 + high expression of CA9 versus T3 + G3G4 + low expression of CA9). Finally, the multivariate regression analysis identified CA9 expression (p = 0.036) as an independent predictor of early metastasis. Our study confirms that the expression level of CA9 gene in conventional RCC is related to metastasis. CA9 may be a potential marker for the prediction of early metastasis after nephrectomy and to guide post-operative follow-up and treatment.Clinical and Experimental Metastasis 01/2007; 24(3):149-55. · 3.52 Impact Factor -
Article: The use of MN/CA9 gene expression in identifying malignant solid renal tumors.
[show abstract] [hide abstract]
ABSTRACT: Small solid renal tumors are increasingly encountered. It is important to determine the malignancy of solid renal tumors for the choice of treatment. MN/CA9 is expressed in malignant renal cells but absent in normal cells. MN/CA9 is one of the most powerful gene markers available for RCC. The objective of this pilot study is to utilize MN/CA9 gene expression in FNA biopsy to determine the malignancy of imaging-indeterminate solid renal tumors. A total of 35 patients with an imaging-indeterminate solid renal mass entered into this study. The molecular protocol consisted of a rapid column extraction of RNA and one-step RT-PCR for the detection of MN/CA9 gene expression. The preoperative molecular diagnosis was compared with postoperative pathology. There were 28 RCCs (19 clear cell carcinomas, 7 papillary carcinomas and 2 chromophobe carcinomas) and 7 benign tumors proved by postoperative pathology. The overall sensitivity and specificity for MN/CA9 were respectively 68% and 100%. MN/CA9 was positive in 16/19 (84%) FNA biopsies of clear cell RCCs. No false positive appeared for MN/CA9 gene expression. Moreover, MN/CA9 gene expression was positive in 8/13 (62%) of false negative or suspect cytology. Detection of MN/CA9 gene expression in FNA biopsy is possible. Its detection can be helpful in identifying the malignancy among renal tumors.European Urology 03/2006; 49(2):401-5. · 8.49 Impact Factor -
Article: Proposal for revision of the TNM classification system for renal cell carcinoma
[show abstract] [hide abstract]
ABSTRACT: BACKGROUND The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system.METHODS The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model.RESULTSThe mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5–6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring ≤ 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with ≤ 5.5-cm incidentally detected RCC; 2) patients with ≤ 5.5-cm symptomatic RCC; and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age.CONCLUSIONS The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint. Cancer 2005. © 2005 American Cancer Society.Cancer 11/2005; 104(10):2116 - 2123. · 4.77 Impact Factor -
Article: Evaluation of a panel of molecular markers for the diagnosis of malignant serous effusions.
[show abstract] [hide abstract]
ABSTRACT: Our main goal was to evaluate a panel of molecular markers for the detection of cancer cells in serous effusions and to determine their value as an adjunctive reverse transcription-PCR (RT-PCR) test to cytologic examination. One hundred fourteen serous effusions from 71 patients with tumors and 43 patients with benign diseases were subjected to RT-PCR for expression of carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (Ep-CAM), E-cadherin, mammaglobin, mucin 1 (MUC1) isoforms MUC1/REP, MUC1/Y, and MUC1/Z, calretinin, and Wilms' tumor 1 susceptibility gene. CEA, Ep-CAM, E-cadherin, and mammaglobin were specifically expressed in malignant effusions. The sensitivity of RT-PCR in cytologically negative malignant effusions was 63.1% combining CEA and Ep-CAM (with 100% specificity) and reached 78.9% adding MUC1/Y or MUC1/Z (with 93% specificity). In the whole population of effusions, the combination of cytology with RT-PCR of CEA and Ep-CAM yielded a 90.1% sensitivity, a specificity and a positive predictive value of 100%, and a 86% negative predictive value for malignancy. Adding MUC1/Y or MUC1/Z to the panel, the sensitivity was 94.5% with 93% specificity, 95.7% PPV, and 90.9% negative predictive value. Moreover, CEA and mammaglobin were specifically expressed in epithelial malignancies, and mammaglobin was mainly expressed in effusions from breast carcinoma (97.3% of specificity). A combination of cytology and RT-PCR analysis of CEA and Ep-CAM significantly improved the detection sensitivity of tumor cells in serous effusions. RT-PCR analysis of CEA, Ep-CAM, and mammaglobin in serous effusions could be a beneficial adjunct to cytology for the diagnosis of malignancy.Clinical Cancer Research 11/2005; 11(19 Pt 1):6862-7. · 7.74 Impact Factor -
Article: Proposal for revision of the TNM classification system for renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: The current study defined an optimal tumor size breakpoint to stratify localized renal cell carcinoma (RCC) into groups with significantly different cancer-related outcomes and proposed a revision of the TNM classification system. The authors analyzed the data from 1138 patients who had undergone partial or radical nephrectomy for localized RCC at 7 European urologic centers. The optimal pathologic size breakpoint was calculated using the martingale residuals from a Cox proportional hazards regression model. The mean follow-up time was 87 months. The scatterplot of tumor size versus expected risk of death per patient suggested that an interval of 5-6 cm was appropriate. A total of 720 (63.3%) and 418 (36.7%) patients had tumors measuring < or = 5.5-cm and tumors measuring > 5.5-cm, respectively. Significant cancer-specific survival differences between the two groups of patients were reported in the series by all the centers participating in the study. On univariate analysis, the other variables found to be associated with cancer-specific survival were the patient's age, symptomatic tumor presentation, and the Fuhrman nuclear grade. On multivariate analysis, the pathologic stage of the primary tumor defined according to the 5.5-cm breakpoint was found to be an independent predictor of cancer-specific survival, as well as age, mode of presentation, and nuclear grade. According to the multivariate analysis, the authors clustered patients into 3 groups with statistically significant outcome differences: 1) patients with < or = 5.5-cm incidentally detected RCC; 2) patients with < or = 5.5-cm symptomatic RCC; and 3) patients with > 5.5-cm RCC. This cancer-related outcome stratification was valid regardless of the patient's age. The 5.5-cm breakpoint was found to be the optimal tumor size breakpoint with which to stratify patients with organ-confined RCC. The study supported the upgrade of the TNM classification system according to this breakpoint.Cancer 11/2005; 104(10):2116-23. · 4.77 Impact Factor -
Article: Multiinstitutional European validation of the 2002 TNM staging system in conventional and papillary localized renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: The current study validated the 2002 edition of the TNM staging system in a multicenter, multinational European series of localized renal cell carcinoma (RCC). The authors analyzed the clinical data of 2217 patients who had undergone radical or partial nephrectomy for localized RCC in 7 urologic centers. In the current study, 1065 patients (48%) were classified as having pT1a disease, 771 (34.8%) were classified as having pT1b disease, and 381 (17.2%) were classified as having pT2 disease. Tumor histotype was conventional RCC in 1886 patients (85%), papillary in 182 (8.2%) patients, chromophobe in 64 (2.9%) patients, and unclassified in 85 (3.8%) patients. The mean follow-up time was 65.36 +/- 52.09 months. The 5 and 10-year disease-specific survival probabilities were 95.3% and 91.4% in patients with pT1a disease, 91.4% and 83.4% in patients with pT1b disease, and 81.6% and 75.2% in patients with pT2 disease (log-rank test P value = 0.0000). The disease-specific survival rates of patients with pT1a RCC were significantly higher than those recorded in patients with pT1b and pT2 RCC. Similarly, the disease-specific survival probabilities of patients with pT1b RCC were significantly better than those of patients with pT2 RCC. Analyzing the seven series individually, the 2002 TNM staging system provided appropriate stratification for only one series. The 2002 TNM staging system allowed significant stratification of the cancer-related outcomes in the subgroup of patients with conventional RCC but not in those with papillary carcinomas. The application of the 2002 TNM staging system in the current multicenter series enabled the authors to demonstrate optimal stratification of patients with localized RCC. Stratifying by tumor histotype, the data coming from the whole group analysis were reconfirmed for clear cell RCC only.Cancer 10/2005; 104(5):968-74. · 4.77 Impact Factor -
Article: Different DNA ploidy patterns for the differentiation of common subtypes of renal tumors.
[show abstract] [hide abstract]
ABSTRACT: The common subtypes of renal tumors are conventional or clear cell carcinoma, papillary carcinoma, chromophobe carcinoma and oncocytoma. Each subtype has its distinct histogenesis and clinical evolution. DNA ploidy is viewed as a marker of gross genomic aberrations. The aim of this study is to evaluate the DNA ploidy in the common subtypes of renal tumors to increase our understanding of renal tumor biology and to broaden clinical application of DNA ploidy. 38 renal tumor samples (13 clear cell RCCs, 12 papillary RCCs, 7 chromophobe RCCs, and 6 oncocytomas) were studied. Five biopsies of different parts of each fresh tumor were subjected to a flow cytometric analysis of DNA ploidy. All tumors except one papillary RCC generated interpretable DNA histograms. Flow cytometric analysis of oncocytomas showed the diploid pattern (29/30 frequencies) while the chromophobe RCC never showed the diploid pattern (0/55 frequencies) (p<0.01). 3/7 chromopbobe RCCs possessed the hypodiploid stemline. The hypodiploid stemline appeared neither in conventional RCCs (0/63 frequencies) nor in papillary RCCs (0/50 frequencies). The diploid pattern was dominant in conventional and papillary RCCs. 10/13 (76.9%) of clear cell RCCs and 9/11 (81.8%) of papillary RCCs possessed a homogeneous DNA ploidy pattern while only 1/7 (14.3%) has a homogeneous DNA ploidy pattern. 6/7 chromophobe RCCs had multiple aneuploid stemlines. Flow cytometric analysis reveals that conventional and papillary RCCs are more homogeneous than chromophobe RCC. Each subtype of renal tumors possesses a specific DNA ploidy pattern. The analysis of DNA ploidy is useful for the differentiation of common subtypes of renal tumors in morphologically difficult cases.Cellular oncology: the official journal of the International Society for Cellular Oncology 02/2005; 27(1):51-6. · 4.17 Impact Factor -
Article: Characteristics of image-detected solid renal masses: implication for optimal treatment.
[show abstract] [hide abstract]
ABSTRACT: Solid renal masses are found increasingly. Further analysis of the characteristics of solid renal masses is useful for optimal treatment. A retrospective analysis of all solid renal masses was conducted from December 1998 to May 2003 at the Urology Department, Central University Hospital of Saint-Etienne, France. A total of 162 solid renal masses were treated. The preoperative imaging diagnosis of ultrasound and computed tomography, and final pathological results were reviewed. One hundred and forty-five tumors were pathologically confirmed to be renal cell carcinomas (RCC); 17 tumors (10.5%) were benign. There were eight renal oncocytomas, eight renal angiomyolipomas and one benign mixed epithelial/stroma tumor. Three oncocytomas and five angiomyolipomas were strongly suspected before surgery. The majority of the benign tumors were < or =4 cm. The percentage of small benign tumors (< or =4 cm) was significantly higher than large benign tumors (>4 cm). Although it is possible to use imaging to detect some benign tumors, the majority of benign tumors cannot be diagnosed definitively by imaging before surgery. Malignancy in solid renal masses is tumor-size related. Benign solid renal tumors appear mainly as small-sized tumors. The preoperative differentiation between an RCC and a benign tumor can be difficult. Our data suggest that a biopsy is necessary in selected patients to achieve the maximum accuracy in order to provide optimal treatment.International Journal of Urology 03/2004; 11(2):63-7. · 1.75 Impact Factor -
Article: Rapid and sensitive detection of messenger RNA expression for molecular differential diagnosis of renal cell carcinoma.
[show abstract] [hide abstract]
ABSTRACT: The aim of this study was to develop a practical technique to detect mRNA expression and to validate a panel of mRNA markers for molecular differential diagnosis of renal cell carcinoma (RCC). The renal cancer cell line SKRC-52 was used to set up the technique, which consisted of column extraction of RNA and one-step reverse transcription-PCR. We validated a panel of gene markers, including MN/CA9, cadherin-6, vimentin, mucin1, and parvalbumin, and studied 50 renal tumors (30 conventional, 9 papillary, and 5 chromophobe RCCs and 6 oncocytomas), 10 normal tissues, and 10 normal blood samples. We mimicked fine needle aspiration (FNA) biopsy in 10 kidneys with conventional RCC and applied this technique to 10 preoperative FNA samples from imaging-indeterminate renal tumors. The technique could detect as few as 10 SKRC-52 cells with MN/CA9 as mRNA marker and was less time consuming and labor intensive. MN/CA9 was a sensitive and rather specific gene marker for conventional RCC. Cadherin-6 gene expression was a sensitive marker for conventional and papillary RCC. Vimentin was highly specific for conventional RCC. Mucin1 mRNA was sensitive for papillary and chromophobe RCC and oncocytoma. Parvalbumin mRNA was a sensitive and highly specific marker for both chromophobe RCC and oncocytoma. Thus, these mRNA markers represent the biomarker genes for the subtypes of renal tumors. Finally, we successfully applied the technique to FNA specimens. Five preoperative FNA samples were MN/CA9 gene positive, suggesting a RCC, whereas the routine cytology was positive in only three cases. A rapid and sensitive assay of mRNA markers was developed for molecular differential diagnosis of RCC. This molecular assay can be used as a powerful ancillary to surgical pathological diagnosis and cytological diagnosis of RCC.Clinical Cancer Research 01/2004; 9(17):6441-6. · 7.74 Impact Factor
Top co-authors
Top Journals
- Cancer (2)
- Anticancer research (2)
- Clinical Cancer Research (2)
- Progrès en Urologie (2)
- Anticancer research (2)
Institutions
-
2009–2013
-
Université Jean Monnet
Saint-Étienne, Rhone-Alpes, France
-
-
2005
-
Università degli studi di Verona
- Section of Cardiology
Verona, Veneto, Italy -
Centre Hospitalier Universitaire de Dijon
Dijon, Bourgogne, France
-
