Multi-omics analysis illuminates MOGS as a key therapeutic target in clear cell renal cell carcinoma

Renal Cell Carcinoma: Diagnosis Based on Metastatic Manifestations

Diagnostic and Prognostic Molecular Markers in Renal Cell Carcinoma

Focus on kidney cancer

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

Characterization of Patients With Metastatic Renal Cell Carcinoma Experiencing Complete Response to First-line Therapies: Results From the International Metastatic Renal Cell Carcinoma Database Consortium.

ESMO Clinical Practice Guideline update on the use of immunotherapy in early stage and advanced renal cell carcinoma

Cytogenetic and molecular genetic techniques have been used in demonstrating the chromosomal abnormalities which characterize specific subtypes of renal cell carcinoma (RCC). The aim of this study was to determine the efficiency of fluorescent in situ hybridization (FISH) technique in characterizing various subtypes of RCC based on the presence of specific chromosome abnormalities found in each RCC subtype. FISH was performed on touch imprint smears from eight renal cell carcinomas histologically confirmed by established criteria. In four tumors with histologic features of chromophobe renal cell carcinoma (ChRCC), interphase FISH was performed using centromeric probes for chromosomes 1, 2, 6, 10, 12, 17 and 21. All four ChRCC tumors showed one FISH signal corresponding to one copy number for each of these chromosomes. Two papillary RCCs included in this study showed trisomy 7 and 17, and loss of chromosome Y, using the corresponding chromosome centromeric probes. Similarly, we tested two clear cell RCCs for chromosome 3 short arm deletion with DNA probe 3p21.3. Both tumors showed loss of 3p21.3 signal. We conclude that interphase FISH performed on touch imprint smears is a relatively simple, rapid and reliable method for detecting chromosome abnormalities which are specific for various subtypes of RCC.

Solid Renal Masses in Transplanted Allograft Kidneys: A Closer Look at the Epidemiology and Management.

Renal cell carcinoma (RCC) is a renal cortical tumor with high clinical incidence. The effect of glutathione peroxidases (GPXs) on RCC and the possible mechanism are still unclear. This study aims to explore the expression level of GPXs gene in RCC and its effect on the clinical prognosis of patients with RCC via bioinformatics analysis. The mRNA expressions of GPXs family genes were obtained from the public data of The Cancer Genome Atlas (TCGA) database. The Kruskal-Wails test was used to analyze the differences in mRNA expression of GPXs family genes between samples from patients with RCC and the normal population. UALAN databases were used to analyze the differences in protein expression of GPXs family genes between samples from patients with renal clear cell carcinoma and the normal population, and to evaluate the role of GPXs family genes in RCC. The Kaplan-Meier Plotter was used to analyze the correlation between different types of RCC and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS). Kaplan-Meier survival curve was drawn based on the GPX8 gene expression to study the relationship between GPX8 gene expression and prognosis of RCC patients. Based on the results of multivariate Cox regression analysis, a Nomogram scoring model for RCC prediction was established by introducing GPX8 gene. The mRNA expressions of GPX1 and GPX4 were higher in the sample of renal chromophobe cell carcinoma, renal clear cell carcinoma, and renal papillary cell carcinoma than those in the normal population (all P<0.01), and GPX7 and GPX8 were significantly over-expressed in patients with renal papillary cell carcinoma and renal clear cell carcinoma (all P<0.01). Compared with the normal group, the protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in renal clear cell carcinoma (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). The protein expressions of GPX1, GPX2, GPX7, and GPX8 were increased significantly in patients with renal clear cell carcinoma at different tumor grades (all P<0.01), while GPX3 and GPX4 expressions were decreased significantly (both P<0.01). Survival analysis showed that OS, DFS, DSS, and PFS were all decreased in patients with clear cell carcinoma compared with patients with papillary cell carcinoma and chromophobe cell carcinoma. According to the GPX8 level, patients were assigned into the low, medium, and high expression groups. Compared with the low GPX8 level group, the OS (P<0.01), DFS (P=0.03), DSS (P<0.01), and PFS (P=3.18×10-7) were significantly decreased in the high level group. Univariate Cox proportional regression analysis showed that the high level of GPX8 was associated with poor OS of 3 different types of renal cancer. Multifactorial analysis showed that GPX8 was an independent factor affecting the OS of patients with renal papillary cell carcinoma. Race and post tumor node metastasis (pTNM) typing were independent factors influencing the OS of patients with renal clear cell carcinoma. GPX8 and pTMN were independent factors influencing the OS of patients with renal chromophobe cell carcinoma. Based on these variables, the Nomogram risk models of 3 types of cell carcinoma were established, and the discrimination and calibration of the models were evaluated using the Consistency index (C-index) and calibration curves. The C-index of the risk model of renal papillary cell carcinoma was 0.62 (95% CI 0.51 to 1.00, P=0.03). The results of receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) was 0.88. The C-index of the risk model of renal clear cell carcinoma was 0.72 (95% CI 0.52 to 1.00, P=0.03). The results of ROC curve showed that the AUC was 0.90. The C-index of the risk model of chromophobe cell carcinoma of kidney was 0.90 (95% CI 0.85 to 1.00, P<0.01). The results of ROC curve showed that the AUC was 0.59. GPXs family genes, especially GPX8, are potential markers for poor prognosis of RCC, and the occurrence and development of RCC can be predicted in clinical practice based on the expressions of GPXs family genes.

Fuhrman Grade Provides Higher Prognostic Accuracy Than Nucleolar Grade for Papillary Renal Cell Carcinoma

miRNA Profiling for Clear Cell Renal Cell Carcinoma: Biomarker Discovery and Identification of Potential Controls and Consequences of miRNA Dysregulation

Renal tumors with clear cells. A review

Objective To screen differentially expressed proteins in serum of patients with renal clear cell carcinoma (RCC) before and after operation by protein chip technique and to explore its clinical significance. Method From October 2015 to October 2016, 89 patients with renal clear cell carcinoma (RCC) who underwent urological surgery in the First Affiliated Hospital of Xinjiang Medical University were selected as the RCC group, and 100 healthy volunteers and non-RCC patients were selected as the control group. The RCC group was followed up for 1 year after operation. Serum differential proteins were detected by surface enhanced laser time of flight mass spectrometry (SELDI-TOF-MS) and CM10 weak cation exchange protein chip. Linear Support Vector Machine (SVM) method was used to establish a protein fingerprint diagnosis model, leaving a cross validation model to identify the effect. The serum differential proteins were analyzed by ZUCI-PDAS protein mass spectrometry data analysis system. Results The protein of mass-charge ratio (M/Z) 2745 was differentially expressed between RCC group and control group, and corresponding protein is Histatin-3, its expression level was lower in RCC group than that in control group before operation (P 0.05). According to the different expression levels of Histone-3 in the two groups, ROC curve analysis showed that the area under the curve(AUC) was 0.804, sensitivity was 86.7%, specificity was 66.7%. A certain boundary of protein expression intensity was used as a marker, the sensitivity of predicting renal clear cell carcinoma was 86.3%(76/89), and the specificity was 88%(88/100). Conclusion The expression of Histone-3 in renal cell carcinoma was different from that in healthy people, and the expression level of Histone-3 increased after operation, suggesting that Histone-3 is correlated with renal cell carcinoma and may become a new molecular marker of renal clear cell carcinoma. Key words: Clear cell renal carcinoma; Proteomics; Histatin-3

Clear cell adenocarcinoma of salivary glands (CCASG) is a relatively rare tumor, composed entirely of clear cells of putative ductal origin. It bears striking morphologic similarities to renal cell carcinoma (RCC) of clear cell type on hematoxylin and eosin stains. Differentiation between CCASG and metastatic RCC to the salivary glands has been considered problematic or even impossible on morphologic grounds. We examined three cases of CCASG and 12 cases of RCC (6 primary and 6 metastatic) by hematoxylin and eosin staining, immunohistochemistry, and electron microscopy. Two distinctive immunohistochemical and ultrastructural patterns emerged from this analysis. CCASG showed positivity for high molecular weight cytokeratin and carcinoembryonic antigen and ultrastructurally showed prominent squamoid differentiation, glycogen pools, and absence of lipid. In contrast, RCC was characterized by positivity for vimentin and complete absence of staining for high molecular weight cytokeratin and carcinoembryonic antigen. On ultrastructural studies, RCC lacked any squamoid differentiation, and the tumor cells contained abundant cytoplasmic lipid in addition to glycogen. Thus, based on the consistent differences on the immunohistochemical staining patterns and their characteristic subcellular morphology, CCASG and RCC can be distinguished on pathologic evaluation. The different direction of differentiation of the cells in CCASG and RCC (i.e., ductal in the former and renal tubular and mesodermal in the latter) results in their distinctive immunophenotypical and ultrastructural features.

Sarcomatoid renal cell carcinoma is not a distinct histologic entity and represents high-grade transformation in different subtypes of renal cell carcinoma. It is not known whether any particular histologic type has a predilection for sarcomatoid change or whether the primary histologic type of renal carcinoma undergoing sarcomatoid change affects prognosis. Of 952 consecutively histologically subtyped renal cell carcinomas, the incidence of sarcomatoid differentiation was 8% in conventional (clear cell) renal carcinoma, 3% in papillary renal carcinoma, 9% in chromophobe renal carcinoma, 29% in collecting duct carcinoma, and 11% in unclassified renal cell carcinoma. One hundred one renal cell carcinomas with sarcomatoid change were studied, and clinicopathologic parameters were correlated with outcome. The mean age of patients was 60 years (range, 33-80 years), and the male-to-female ratio was 1.6:1. The median tumor size was 9.2 cm (range, 3-25 cm). The primary histologic subtype of the carcinoma component was conventional (clear cell) renal carcinoma in 80 cases, papillary renal carcinoma in eight, chromophobe renal carcinoma in seven, collecting duct carcinoma in two, and unclassified renal cell carcinoma in four. The sarcomatoid component resembled fibrosarcoma in 54 cases, malignant fibrous histiocytoma in 44, undifferentiated sarcoma (not otherwise specified) in three with focal rhabdomyosarcomatous component in two of them. The spindled elements accounted for 1% to 99% of the sampled tumor (median, 40%; mean 45%). The histologic grade of the spindled elements was intermediate to high in 92 cases and low in nine cases. Most cases were TNM stages III and IV (seven stage I, six stage II, 63 stage III, and 25 stage IV). Follow-up was available in 88 patients; 61 (69%) patients died of disease and had a median survival time of 19 months. Distant metastases, most frequently to the lungs, were documented in 51 (66%) of 77 patients who had available clinical information regarding distant metastasis. The disease-specific survival rate was 22% and 13% after 5 and 10 years, respectively, compared with a cohort of renal cell carcinomas without sarcomatoid change with a 5-and 10-year disease-specific survival of 79% and 76%, respectively. Kaplan-Meier survival analysis showed that tumors with high TNM stage (p = 0.0027), at least 50% sarcomatoid component (p = 0.0453), and angiolymphatic invasion (p = 0.0282) were associated with decreased survival rates. The primary histologic subtype of the carcinoma component and the type and grade of the sarcomatoid component did not affect survival. In a Cox proportional hazard regression model, TNM stage appeared to be the only significant variable in predicting outcome among renal cell carcinomas with sarcomatoid change (p = 0.018; risk ratio, 6.984 and 8.439). Compared with a cohort of renal cell carcinomas without sarcomatoid change, sarcomatoid tumors tended to present at a more advanced stage (p = 0.0001). Also, when adjusted for stage, necrosis, and tumor size, patients with tumors with sarcomatoid differentiation had a worse prognosis than did patients with tumors without sarcomatoid change (p = 0.0001). In conclusion, sarcomatoid change in renal cell carcinoma portends a worse prognosis. Because tumors with even a small component of sarcomatoid change may have an adverse outcome, this finding, when present, should be noted in the surgical pathology report.