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1.
Urol Oncol ; 32(8): 1272-6, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24996774

ABSTRACT

INTRODUCTION: A disintegrin and metalloproteinase-17 (ADAM17) plays an important role in biological activity in different cancers. Its expression and prognostic value have not been studied in clear cell renal cell carcinoma (cRCC). The objective of this study was to explore the prognostic value of ADAM17 in patients with cRCC. MATERIALS AND METHODS: A total of 131 patients with cRCC were studied. There were 90 men and 41 women, with an average age of 67 years (range: 34-93 y). There were 110 patients with localized disease and 21 patients with metastatic disease. The expression of ADAM17 was evaluated by immunohistochemistry with a monoclonal antibody. The follow-up varied from 4.2 to 184 months, with a median of 72 months for patients with localized disease. Kaplan-Meier with a log-rank test was performed to compare the progression-free survival after surgery. The univariate and multivariate analyses were performed to examine the significance of ADAM17 expression for the patient's progression-free survival. RESULTS: The ADAM17 expression was found in 109/131 tumors. The ADAM17 expression was found in 20/21 metastatic tumors and in 89/110 localized tumors. Regarding patients with localized tumors, 31 patients experienced a recurrence or death during follow-up. The Kaplan-Meier analysis revealed that the high expression of ADAM17 was associated with a reduced progression-free survival (P = 0.005). The univariate logistic regression analysis indicated that the high expression of ADAM17 was associated with the disease progression (hazard ratio = 2.826; 95% CI: 1.324-6.034; P = 0.007). The high expression of ADAM17 remained a significant factor for decreased progression-free survival in multivariate analysis. CONCLUSION: ADAM17 was frequently expressed in cRCC. The high expression of ADAM17 was correlated with a worse outcome for patients with cRCC. ADAM17 is a new biomarker for the management of patients with cRCC.


Subject(s)
ADAM Proteins/metabolism , Biomarkers, Tumor/metabolism , Carcinoma, Renal Cell/enzymology , Kidney Neoplasms/enzymology , ADAM17 Protein , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kidney Neoplasms/pathology , Male , Middle Aged , Prognosis
2.
Histol Histopathol ; 28(9): 1217-22, 2013 09.
Article in English | MEDLINE | ID: mdl-23609324

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.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/metabolism , Gene Expression Regulation, Neoplastic , Kidney Neoplasms/diagnosis , Kidney Neoplasms/metabolism , Receptors, CXCR4/metabolism , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/metabolism , Female , Humans , Immunohistochemistry , Male , Middle Aged , Multivariate Analysis , Prognosis , Time Factors
3.
Urol Oncol ; 30(4): 463-8, 2012.
Article in English | MEDLINE | ID: mdl-20822935

ABSTRACT

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSIONS: 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.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Carbonic Anhydrases/metabolism , Carcinoma, Renal Cell/enzymology , Cysts/enzymology , Kidney Diseases, Cystic/enzymology , Kidney Neoplasms/enzymology , Adult , Aged , Aged, 80 and over , Carbonic Anhydrase IX , Carcinoma, Renal Cell/diagnosis , Cyst Fluid/enzymology , Cysts/diagnosis , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Kidney/enzymology , Kidney/pathology , Kidney Diseases, Cystic/diagnosis , Kidney Neoplasms/diagnosis , Male , Middle Aged
4.
Ann Pathol ; 30(5): 382-5, 2010 Oct.
Article in French | MEDLINE | ID: mdl-21055526

ABSTRACT

Splenosis corresponds to an autotransplantation of splenic tissue, consecutive to a traumatic or surgical wound of the spleen. The peritoneal cavity is usually affected but intrathoracic nodules are also described, when simultaneous rupture of the spleen and diaphragmatic laceration exist. Diaphragmatic laceration may be subclinical. Lesions are generally asymptomatic and are a fortuitous finding in radiographs or by the surgeons in the majority of the cases. We report a case of pleural and pulmonary splenosis, mimicking pleural and pulmonary metastasis of a dorsal melanoma.


Subject(s)
Lung Neoplasms/pathology , Lung Neoplasms/secondary , Pleural Neoplasms/pathology , Pleural Neoplasms/secondary , Splenosis/pathology , Aged , Diagnosis, Differential , Humans , Male , Thorax
5.
Eur J Cancer ; 46(18): 3141-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20709527

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.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Carbonic Anhydrases/metabolism , Carcinoma, Renal Cell/diagnosis , Kidney Neoplasms/diagnosis , Antineoplastic Agents/therapeutic use , Biological Assay , Biomarkers, Tumor/antagonists & inhibitors , Cancer Vaccines/therapeutic use , Carbonic Anhydrase IX , Cell Hypoxia/physiology , Enzyme Inhibitors/therapeutic use , Humans , Immunohistochemistry , Immunotherapy/methods , Interleukin-2/therapeutic use , Prognosis , Radioimmunotherapy/methods
6.
Neuropathology ; 30(3): 232-40, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19925562

ABSTRACT

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL) with extranodal location affecting only the CNS, meninges and eye, without visceral or lymph node involvement. Its incidence has increased sharply over the past three decades, especially in immunocompetent subjects. Most PCNSL cases are diffuse large B-cell lymphomas (DLBCLs). However, it differs from nodal DLBCL in that it has a worse prognosis. DLBCLs are a heterogeneous entity and according to new genomic discoveries, classifications into prognostic subgroups have been embarked upon. Two prognostic algorithms were then prepared using a panel of immunohistochemical markers (CD10, Bcl6, MUM1/IRF-4, and Bcl2), thus categorizing DLBCL into two subgroups, GCB (germinal centre B-cell-like) or non-GCB, and into Group 1 or Group 2. Our goal is to apply both of these two sub-classifications to 39 PCNSLs, in order to assess their usefulness and prognostic relevance. 74.3% of our PCNSLs were of a non-GCB phenotype, corresponding to an activated postgerminal origin. They were evenly distributed across G1 and G2. Two- and 5-year overall survival rates were 34.8% and 19.6%, respectively. Younger age (<65) and a therapeutic combination of chemotherapy and radiotherapy significantly improved our patients' survival rates. The other clinical or biological markers tested had no prognostic impact. The two classifications did not reveal any significant survival difference. The recent discovery of a specific "transcriptional signature" of PCNSL, marking them out of DLBCL could account for the irrelevance of such prognostic classifications to PCNSL.


Subject(s)
Central Nervous System Neoplasms/chemistry , Central Nervous System Neoplasms/immunology , Lymphoma, B-Cell/chemistry , Lymphoma, B-Cell/immunology , Lymphoma, Non-Hodgkin/chemistry , Lymphoma, Non-Hodgkin/immunology , Aged , Aged, 80 and over , Central Nervous System Neoplasms/mortality , Databases, Factual/trends , Female , Follow-Up Studies , Humans , Lymphoma, B-Cell/mortality , Lymphoma, Non-Hodgkin/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate/trends
7.
Histopathology ; 54(7): 880-4, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19469910

ABSTRACT

AIMS: 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. METHODS AND RESULTS: 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). CONCLUSION: 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.


Subject(s)
Antigens, Neoplasm/metabolism , Biomarkers, Tumor/metabolism , Carbonic Anhydrases/metabolism , Kidney Diseases, Cystic/diagnosis , Kidney Diseases, Cystic/enzymology , Kidney Neoplasms/diagnosis , Kidney Neoplasms/enzymology , Biopsy, Fine-Needle , Carbonic Anhydrase IX , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/enzymology , Cyst Fluid/enzymology , Diagnosis, Differential , Enzyme-Linked Immunosorbent Assay , Female , Humans , Kidney Diseases, Cystic/diagnostic imaging , Kidney Neoplasms/diagnostic imaging , Male , Middle Aged , Tomography, X-Ray Computed
8.
J Urol ; 180(2): 510-3; discussion 513-4, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18550116

ABSTRACT

PURPOSE: We explored the clinical usefulness of serum carbonic anhydrase 9 as a potential biomarker for conventional renal cell cancer. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Carbonic Anhydrases/blood , Carcinoma, Renal Cell/enzymology , Kidney Neoplasms/enzymology , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/mortality , Aged , Aged, 80 and over , Analysis of Variance , Biopsy, Needle , Carbonic Anhydrase IX , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Cohort Studies , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Nephrectomy/adverse effects , Nephrectomy/methods , Postoperative Complications , Prognosis , Proportional Hazards Models , ROC Curve , Risk Assessment , Sensitivity and Specificity , Statistics, Nonparametric , Survival Analysis , Treatment Outcome
9.
Anticancer Res ; 28(1A): 321-6, 2008.
Article in English | MEDLINE | ID: mdl-18383864

ABSTRACT

BACKGROUND: Reliable serum biomarkers for differential diagnosis of conventional renal cell carcinoma (RCC) are highly desirable. Recent studies have confirmed the stability of circulating RNA in serum of cancer patients. The purpose of our study was to evaluate whether the amounts of circulating RNA could discriminate between conventional renal cancer patients and healthy individuals as a tumor marker. PATIENTS AND METHODS: A total of 71 patients with conventional RCC, 12 with renal oncocytomas and 44 healthy individuals entered into this study. Serum samples were taken and subjected to RNA extraction. The amount of RNA was quantified spectrophotometrically. Additionally, 9 serum samples from conventional RCC were also studied one week after nephrectomy. Diagnostic performance of RNA concentration was calculated through the receiver operating characteristic (ROC) curve to distinguish between conventional RCC and healthy individuals. RESULTS: The mean level of RNA in conventional RCC (1414.19 +/- 91.95 ng/ml) was significantly higher than that in healthy individuals (520.49 +/- 39.75 ng/ml, p<0.0001) and these with renal oncocytomas (560.71 +/- 69.54 ng/ml, p<0.0001). Among the conventional RCC, there was no significant difference in circulating RNA levels in terms of tumor stage, grade or size. The area under the ROC curve was 0.956 (95% confidence interval, 0.923 to 0.989), indicating an acceptable sensitivity and specificity as a tumor marker. For conventional RCC, the RNA level was reduced significantly (p<0.0001) one week after nephrectomy. CONCLUSION: The data suggest that elevated circulating RNA may be a valuable diagnostic tool for discriminating conventional RCC patients from normal individuals or from these with renal oncocytoma. Elevated serum circulating RNA provides a new research area as biomarker for the diagnosis of conventional RCC.


Subject(s)
Carcinoma, Renal Cell/blood , Kidney Neoplasms/blood , RNA, Neoplasm/blood , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Carcinoma, Renal Cell/genetics , Female , Humans , Kidney Neoplasms/genetics , Male , Middle Aged , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction
10.
Fertil Steril ; 90(2): 443.e1-4, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18023440

ABSTRACT

OBJECTIVE: To optimize the management of patients with cancer in a single testis and azoospermia. DESIGN: Case report. SETTING: Reproductive biology department. PATIENT(S): Two male patients referred in an emergency context for gamete cryopreservation before castration for cancer in a single testis; the patients were azoospermic before any sterilizing treatment. INTERVENTION(S): Testicular sperm extraction (TESE) was carried out synchronously with orchiectomy, allowing the cryopreservation of testicular spermatozoa. MAIN OUTCOME MEASURE(S): One year after the end of the cancer treatment, thawed testicular spermatozoa were successfully used in an intracytoplasmic sperm injection procedure. A twin pregnancy was obtained, and a healthy boy and girl were born. CONCLUSION(S): TESE and cryopreservation could be offered to every patient with cancer in a single testis and azoospermia.


Subject(s)
Azoospermia/complications , Testicular Neoplasms/surgery , Cryopreservation , Female , Humans , Male , Orchiectomy , Pregnancy , Semen Preservation , Sperm Injections, Intracytoplasmic , Testicular Neoplasms/complications , Testis/surgery , Tissue and Organ Harvesting
11.
Fertil Steril ; 89(2): 444-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17681330

ABSTRACT

OBJECTIVE: To evaluate the predictive value of seminal inhibin B and anti-Müllerian hormone (AMH) on the outcome of testicular sperm extraction (TESE) in patients with nonobstructive azoospermia. DESIGN: Prospective study. SETTING: Reproductive biology department. PATIENT(S): Forty-seven normospermic, 28 oligozoospermic, and 68 azoospermic patients. INTERVENTION(S): Testicular sperm extraction. MAIN OUTCOME MEASURE(S): Seminal inhibin B and AMH measure. RESULT(S): The seminal values of inhibin B and AMH are widely dispersed. Both inhibin B and AMH seminal values are significantly different between the three groups. The average rates of seminal AMH (not inhibin B) differ significantly according to the etiology of the azoospermia. Both seminal markers are correlated. A significant positive correlation could be observed between the seminal inhibin B and the sperm count, but not for AMH. A significant correlation also exists between seminal and serum inhibin B. The predictive value for TESE outcome of each parameter is rather low. Conversely, a logistic regression combining serum FSH, seminal inhibin B, and AMH produced a satisfying area under the curve of 0.985. CONCLUSION(S): Seminal inhibin B and AMH values are proposed. Separately, seminal markers are poor predictors of TESE outcome. A logistic regression model led to a satisfying area under the curve of 0.985.


Subject(s)
Anti-Mullerian Hormone/analysis , Anti-Mullerian Hormone/physiology , Azoospermia/diagnosis , Inhibins/analysis , Inhibins/physiology , Semen/chemistry , Adult , Anti-Mullerian Hormone/metabolism , Azoospermia/etiology , Azoospermia/metabolism , Humans , Inhibins/metabolism , Male , Middle Aged , Predictive Value of Tests , Prognosis , Semen/metabolism , Sperm Retrieval , Treatment Outcome
13.
Clin Exp Metastasis ; 24(3): 149-55, 2007.
Article in English | MEDLINE | ID: mdl-17390110

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.


Subject(s)
Antigens, Neoplasm/genetics , Carbonic Anhydrases/genetics , Carcinoma, Renal Cell/genetics , Kidney Neoplasms/genetics , Biomarkers, Tumor , Carbonic Anhydrase IX , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Gene Expression , Humans , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Neoplasm Metastasis , Reverse Transcriptase Polymerase Chain Reaction , Survival Rate
14.
Eur Urol ; 49(2): 401-5, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16387417

ABSTRACT

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Detection of MN/CA9 gene expression in FNA biopsy is possible. Its detection can be helpful in identifying the malignancy among renal tumors.


Subject(s)
Antigens, Neoplasm/analysis , Biomarkers, Tumor/analysis , Carbonic Anhydrases/analysis , Kidney Neoplasms/chemistry , Kidney Neoplasms/pathology , Adenocarcinoma, Clear Cell/chemistry , Adenocarcinoma, Clear Cell/pathology , Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Biopsy , Carbonic Anhydrase IX , Carbonic Anhydrases/genetics , Carcinoma, Papillary/chemistry , Carcinoma, Papillary/pathology , Carcinoma, Renal Cell/chemistry , Carcinoma, Renal Cell/pathology , Cytological Techniques , False Positive Reactions , Female , Gene Expression Regulation, Neoplastic , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Pilot Projects , RNA, Neoplasm/analysis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity
15.
Clin Cancer Res ; 11(19 Pt 1): 6862-7, 2005 Oct 01.
Article in English | MEDLINE | ID: mdl-16203775

ABSTRACT

PURPOSE: 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. EXPERIMENTAL DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.


Subject(s)
Biomarkers, Tumor , Genetic Predisposition to Disease , Pleural Effusion, Malignant/genetics , Pleural Effusion, Malignant/metabolism , Aged , Antigens/biosynthesis , Antigens, Neoplasm/biosynthesis , Ascites/metabolism , Cadherins/biosynthesis , Calbindin 2 , Carcinoembryonic Antigen/biosynthesis , Carcinoma/metabolism , Cell Adhesion Molecules/biosynthesis , Cell Line, Tumor , DNA Primers/chemistry , Epithelial Cell Adhesion Molecule , Female , Genes, Wilms Tumor , Glycoproteins/biosynthesis , Humans , Male , Mammaglobin A , Middle Aged , Mucin-1 , Mucins/biosynthesis , Neoplasm Proteins/biosynthesis , Oligonucleotides, Antisense/chemistry , Pleural Effusion , RNA/metabolism , Reverse Transcriptase Polymerase Chain Reaction , S100 Calcium Binding Protein G/biosynthesis , Sensitivity and Specificity , Uteroglobin/biosynthesis , WT1 Proteins/biosynthesis
16.
Anticancer Res ; 25(1A): 377-81, 2005.
Article in English | MEDLINE | ID: mdl-15816561

ABSTRACT

BACKGROUND: Dissemination of cancer cells into the circulation is an essential step in the development of a metastasis. Detection of circulating cancer cells may improve the monitoring methods for cancer patients. However, the detection of circulating renal cancer cells is mainly hampered by the lack of markers available for renal cell carcinoma (RCC). In this study, we evaluated cadherin-6 mRNA as a new molecular marker for the detection of circulating renal cancer cells. MATERIALS AND METHODS: Forty-six blood samples of conventional RCCs were included. A standard protocol of RT-PCR, assisted by computer densitometric analysis to establish a cut-off, was performed to examine cadherin-6 mRNA expression by using specific primers. A renal cancer cell line, SKRC-59 and forty tumor biopsies from conventional RCCs were used as positive controls. Twenty-five blood samples from non-RCC patients were also analyzed. RESULTS: Cadherin-6 mRNA could be detected in 38140 (95%) conventional RCC specimens. Cadherin-6 mRNA was positive in 21/46 (45.7%) blood samples of RCC patients, while no positivity was found in non-RCC blood samples. Among the localized RCCs, 14/35 (40.0%) blood samples were positive while 7/11 (63.6%) were positive among the blood samples from metastatic RCCs. CONCLUSION: Our data indicate that cadherin-6 gene is frequently expressed in conventional RCCs. Cadherin-6 is a useful molecular marker to detect the circulating cancer cells disseminated from conventional RCC.


Subject(s)
Biomarkers, Tumor/biosynthesis , Cadherins/biosynthesis , Carcinoma, Renal Cell/blood , Kidney Neoplasms/blood , Neoplastic Cells, Circulating , Biomarkers, Tumor/genetics , Cadherins/genetics , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Gene Expression , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Neoplasm Metastasis , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction
17.
Cell Oncol ; 27(1): 51-6, 2005.
Article in English | MEDLINE | ID: mdl-15750207

ABSTRACT

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/genetics , DNA/analysis , Kidney Neoplasms/diagnosis , Kidney Neoplasms/genetics , Ploidies , Adenocarcinoma, Clear Cell/genetics , Adenoma, Chromophobe/genetics , Adenoma, Oxyphilic/genetics , Biopsy , Carcinoma, Papillary/genetics , Cell Differentiation , Chromosome Aberrations , DNA/metabolism , DNA, Neoplasm/analysis , Flow Cytometry/methods , Humans , Neoplasm Metastasis
18.
Int J Urol ; 11(2): 63-7, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14706008

ABSTRACT

BACKGROUND: Solid renal masses are found increasingly. Further analysis of the characteristics of solid renal masses is useful for optimal treatment. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Carcinoma, Renal Cell/pathology , Diagnostic Imaging/methods , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Adenoma, Oxyphilic/pathology , Adenoma, Oxyphilic/surgery , Aged , Angiolipoma/pathology , Angiolipoma/surgery , Biopsy, Needle , Carcinoma, Renal Cell/diagnosis , Carcinoma, Renal Cell/surgery , Cohort Studies , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Kidney Neoplasms/diagnosis , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Staging , Nephrectomy/methods , Predictive Value of Tests , Probability , Retrospective Studies , Sensitivity and Specificity , Statistics, Nonparametric , Tomography, X-Ray Computed
19.
Clin Cancer Res ; 9(17): 6441-6, 2003 Dec 15.
Article in English | MEDLINE | ID: mdl-14695146

ABSTRACT

PURPOSE: 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). EXPERIMENTAL DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.


Subject(s)
Carcinoma, Renal Cell/diagnosis , Kidney Neoplasms/diagnosis , RNA, Messenger/metabolism , Adenoma, Oxyphilic/metabolism , Biomarkers, Tumor , Biopsy , Cadherins/biosynthesis , Carcinoma, Renal Cell/metabolism , Cell Line, Tumor , Diagnosis, Differential , Humans , Kidney Neoplasms/metabolism , Mucin-1/biosynthesis , Parvalbumins/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Time Factors , Vimentin/biosynthesis
20.
J Am Acad Dermatol ; 49(3): 527-9, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12963924

ABSTRACT

Malignant Langerhans cell tumor is a rare malignant proliferation of Langerhans cells, with a negative prognosis due to its dissemination throughout the body, leading to death within 1 year. This disease has to be distinguished from Langerhans cell histiocytosis. The favorable evolution of a case of Langerhans cell tumor, characterized by the absence of metastasis 18 months after its occurrence, may be due to the initial treatment, which consisted of complete and large resection of the tumor. The authors searched for abnormal dendritic cells or progenitors in the blood but found no large amounts or proliferation of CD34(+) or CD1a(+) cells at the diagnosis and 1 year later. This case report shows that malignant Langerhans cell tumor is not always a lethal disease. The condition may be related to surgical treatment and the absence of malignant cells in the blood when the diagnosis was performed.


Subject(s)
Dendritic Cells/pathology , Histiocytosis, Langerhans-Cell/pathology , Skin Neoplasms/pathology , Adult , Biopsy, Needle , Cell Division/physiology , Dendritic Cells/physiology , Female , Histiocytosis, Langerhans-Cell/physiopathology , Humans , Immunohistochemistry , Prognosis , Risk Assessment , Skin Neoplasms/physiopathology
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