Primary central nervous system lymphoma: immunohistochemical profile and prognostic significance.

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.

[Thoracic splenosis mimicking pleural and pulmonary metastasis]. / Splénose thoracique mimant une atteinte pleuropulmonaire métastatique.

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.

CA9 level in renal cyst fluid: a possible molecular diagnosis of malignant tumours.

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.

Serum carbonic anhydrase 9 level is associated with postoperative recurrence of conventional renal cell cancer.

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.

Elevated serum-circulating RNA in patients with conventional renal cell cancer.

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.

CA9 gene expression in conventional renal cell carcinoma: a potential marker for prediction of early metastasis after nephrectomy.

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.

Evaluation of a panel of molecular markers for the diagnosis of malignant serous effusions.

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.

Different DNA ploidy patterns for the differentiation of common subtypes of renal tumors.

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.

Cadherin-6 gene expression in conventional renal cell carcinoma: a useful marker to detect circulating tumor cells.

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.

Rapid and sensitive detection of messenger RNA expression for molecular differential diagnosis of renal cell carcinoma.

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.

The in vivo DNA aneuploidization during expansion of conventional renal cell carcinoma.

Although numerous studies on the prognostic value of DNA aneuploidy in RCC have been reported, the in vivo DNA aneuploidization during RCC expansion has not been revealed. The present study was undertaken to observe the DNA aneuploidization during RCC expansion. We studied prospectively 67 consecutive conventional RCCs. The ploidy status was determined by analyzing five fresh tumor tissues from different areas by flow cytometry. The diploid, heterogeneous aneuploid tumors and homogeneous aneuploid tumors could be detected, respectively, in 44.8%, 23.9% and 31.3% of cases. The diploid tumors decreased significantly and aneuploid tumors increased significantly as the tumor expanded. The similar DNA content distribution was found between the heterogeneous aneuploid tumors and homogeneous aneuploid tumors. The hypertriploid clone was the most frequent in aneuploid tumors. The tumors of multiple aneuploid clones (16.4%) were mainly found in large-sized tumors. These results suggested that some RCCs underwent DNA aneuploidization during the tumor expansion and that a major route of aneuploidiztion (hypertriploidization) and several pathways existed. Our results also supported the idea that the progressive chromosomal instability was associated with continued tumor growth of RCC. The molecular mechanism and the clinical significance of aneuploidy phenotypes need to be further investigated.

[Molecular and cytometric analysis of renal cell carcinoma cells. Concepts, techniques and prospects]. / Analyse moléculaire et cytométrique des cellules d'adénocarcinome rénal. Concepts, techniques et perspectives.

At the present time, there is no reliable laboratory marker for the diagnosis and prognosis of clear cell renal cell carcinoma (RCC), while about 20% of small tumours detected by modern imaging techniques are benign and the clinical course is difficult to predict with considerable differences for the same stage and same grade. The molecular identification of clear cell RCC cells could satisfy these new requirements in the context of diagnosis of atypical or small renal tumours, allowing a more refined prognostic assessment, which is currently uncertain. Some of the antigens used for molecular diagnosis of clear cell RCC, such as cadherin-6, are present in the normal kidney, while others are newly formed antigens (TuM2PK, MN/CA9, CA12, calpain) or ectopic (PSMA, PSA, KLKI, cytokeratin 7 vimentin) or induce abnormal glycosylation (sialyl Lewis'X, galectins) indicating the malignant nature of the cells. The tumour's capacity for progression is related to dysregulations of the cycle (ras, Pax2, Tiam 1, waf/p21), division (tetracyclines, MIB1, PCNA, Nor Ag), apoptosis (bcl2, p53, CD95/Apo1), and the capacities for tissue invasion (proteases), disorganization (cadherin, catenins) or nidation (ICAM-1, CD44). Finally, chromosomal anomalies (mutations, translocations) also occur. MN/CA9, cadherin-6, vimentin, mucin 1 and DNA content are particularly useful for the diagnosis and/or prognosis of clear cell RCC. These markers can be analysed by extremely sensitive cytometric (flow cytometry, plate cytometry) or molecular methods (RT-PCR, in situ hybridization). These techniques lower the limit of detection of tumour cells in biological products (aspiration cytology, microbiopsy) and eventually in circulating blood. Proteomic and genomic methods (biochips) should considerably accelerate research in this field leading to the development of routine clinical applications.

A novel marker ADAM17 for clear cell renal cell carcinomas: implication for patients' prognosis.

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.

Prognostic value of CXCR4 expression in patients with clear cell renal cell carcinoma.

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.

CA9 as a molecular marker for differential diagnosis of cystic renal tumors.

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.

Carbonic anhydrase 9 in clear cell renal cell carcinoma: a marker for diagnosis, prognosis and treatment.

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.

Significance of inhibin B and anti-Müllerian hormone in seminal plasma: a preliminary study.

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.

Testicular sperm extraction in a single cancerous testicle in patients with azoospermia: a case report.

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.