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

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

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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.

  • Discussion
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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.

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Diffusion weighted imaging in differentiation of the clear cell RCC from the major non-clear cell RCC subtypes
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Introduction. Renal cell carcinoma (RCC) is the most common malignant renal tumor in adults accounting for 80-90% of primary malignant adult renal neoplasms. RCC represents a very heterogenous groups of tumors with a number of distinct histological varieties, of which the major 3 subtypes are clear cell RCC (70-80%), papillary RCC (13-20%), and chromophobe RCC (5%). Imaging features are varied from solid and relatively homogenous appearance to markedly heterogenous appearance with cystic changes, hemorrhage and necrosis. The use of diffusion weighted imaging (DWI) for RCC subtyping and also for differentiation of high grade and low grade tumors has been showed to be useful in many studies in the literature. Aim. In this study, we aimed to determine the comparative contribution of DWI in differentiation of the clear cell RCC from the major non-clear cell RCC subtypes at standard high b-value (1000 s/mm2) versus low b-value (500 s/mm2). In addition, we also aimed to assess the diagnostic performance of DWI for differentiating high grade clear cell RCC from low grade clear cell RCC based on Fuhrman grades in our patients. Material and methods. 62 cases with a prediagnosis of RCC according to MRI findings including DWI sequence with histological verification and subtyping of renal cortical tumor following a total or partial nephrectomy were included in the study. Results. Among 62 cases, 46 were male and 16 were female, with mean age of 59.5 ± 15.7. Pathological diagnoses of 62 cases were as follows, clear cell RCC, (44) papillary cell RCC (14) and chromophobe cell RCC (4). They were divided into two groups as clear cell RCC group (44 cases) and non-clear cell RCC group (18 cases). There was no statistically significant difference between the mean ADC values of clear cell and non-clear cell groups at b-value of 1000 s/mm2 (p&gt;0.05). However, the mean ADC level for clear cell RCC group at b-value of 500 s/mm2 were significantly higher than for non-clear cell RCC group (p&lt;0.05). When a value of 0.99x10-3 mm2/s was set as cut-off for ADC at b-factor of 500 s/mm2, differentiation was achieved with a high sensitivity (91%) and specificity (56%). Regarding the diagnostic performance of DWI for differentiating high from low Fuhrman grades clear cell RCCs, there was no statistically significant difference between the ADC values of Grade I-II clear cell RCC cases and Grade III-IV clear cell RCC cases at b-factor of 1000 s/mm2 (p&gt;0.05). However, ADC values for grade III-IV group was statistically significantly lower than ADC values for Grade I-II group at b-factor of 500 s/mm2 level. Conclusion. ADC measurements at moderate b-value of 500 s/mm2 were more sensitive in subtyping and grading of RCC cases. This technique can be used in clinical practice as a fast and additional sequence in abdominal MRI.

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