Aims
Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia‐associated transcription factor family on chromosome Xp11.2. Dual‐colour break‐apart fluorescence in‐situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA‐binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10–TFE3 fusion results from paracentric inversion. RBM10–TFE3 RCC may yield a false‐negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10–TFE3 RCC.
Methods and results
Ten patients with RBM10–TFE3 RCC aged 31–71 years were investigated. Histological analysis, immunostaining, dual‐colour break‐apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis.
Conclusions
The present study suggests that the carcinogenesis of RBM10–TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10–TFE3 RCC should be considered, as five patients experienced metastases.
BACKGROUND: Vesical Imaging-Reporting And Data System (VI-RADS) was proposed to detect muscle-invasive bladder cancer (MIBC). OBJECTIVE: To evaluate the performance of VI-RADS and additional value of apparent diffusion coefficient (ADC) values measured on diffusion-weighted magnetic resonance imaging (MRI) for detecting MIBC. METHODS: A total of 176 patients undergoing MRI (multiparametric in 97 [55%] and biparametric in 79 [45%]) before transurethral resection of bladder tumor for primary bladder cancer were retrospectively identified. MRI findings were scored according to VI-RADS. The standardized tumor ADC (sT-ADC: tumor ADC/gluteus maximus ADC) was calculated and used to account for the incompatibility among different MRI protocols. The accuracy of VI-RADS, sT-ADC and their combination to detect MIBC was assessed using the AUC of the ROC curve. RESULTS: MIBC was pathologically confirmed in 46 patients (26%). AUC of VI-RADS to detect MIBC was 0.86. When cut-off of VI-RADS was set at≥3 and≥4, sensitivity/specificity were 78% /70% and 63% /96%, respectively. A lower sT-ADC (≤0.894) was significantly associated with muscle invasion (p < 0.01, AUC 0.79) with sensitivity 78% and specificity 79%. Combination of VI-RADS and sT-ADC improved the accuracy (AUC 0.94); sensitivity was 100% when VI-RADS≥3 or sT-ADC≤0.894 was considered positive, and specificity was 99% when VI-RADS≥4 and sT-ADC≤0.894 was considered positive. Incorporation of sT-ADC reduced under-staging of MIBC as VI-RADS < 3 by 100% and over-staging of non-MIBC as VI-RADS≥4 by 80%. CONCLUSIONS: Incorporation of ADC values into VI-RADS improves accuracy to detect MIBC in primary bladder cancer patients.
Purpose:
Glucose is a major energy resource for tumor cell survival and growth, and its influx into cells is mainly carried out by facilitative glucose transporters (GLUTs). Sodium - dependent glucose transporters (SGLTs) have been highlighted as playing important roles in diabetic treatment. However, their potential roles in cancer remain unclear. We examined expression patterns of SGLTs in tumor tissues together with conventional pathological variables to determine prognostic significance in patients with renal cell carcinoma (RCC).
Materials and Methods:
Nephrectomy specimens were obtained from 68 patients. GLUT - 1, - 2 and SGLT - 1, - 2 expression in tumor and adjacent normal tissues were analyzed by immunohistochemical staining, and intensity was quantified using an image analyzer.
Results:
The four glucose transporters evaluated were broadly distributed in tumor tissues as well as throughout the normal parenchyma. There was no significant correlation between transporter expression and conventional pathological variables. However, increased SGLT - 2 expression was significantly associated with shorter overall survival (p < 0.01), regardless of metastatic status.
Conclusions:
We propose possible prognostic significance of SGLT - 2 expression in human RCC. Given that glucose is a major energy resource for tumor cells and that glucose transport is largely mediated by SGLT, SGLT - 2 may serve as a possible therapeutic target in RCC.
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