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@# Objective: To investigate the effect of long non-coding RNA (lncRNA) lung cancer associated transcript 1 (LUCAT1) on proliferation and migration of clear cell renal cell carcinoma (ccRCC) 786-O cells and the underlying mechanism. Methods: A total of 40 pairs of pathologically confirmed tumor tissues and corresponding adjacent normal tissues from ccRCC patients, who underwent surgical resection in the Department of Urology, the First People's Hospital of Yichang during June 2013 and June 2017, were selected for this study. ccRCC cell lines (786-O, ACHN, UM-RC-2) and normal renal epithelial KiMA cells were also used in this study. qPCR was used to detect the mRNA expressions of LUCAT1, miR-199a-5p and hypoxia inducible fator 1α (HIF-1α) in above mentioned tissues and cell lines; CCK-8 assay was used to evaluate the proliferation of 786-O cells; Transwell assay was used to evaluate the migration of 786-O cells; Dual luciferase reporter gene assay was performed to validate the relationship between LUCAT1 and miR-199a-5p; and Western blotting was conducted to detect the effect of LUCAT1 and miR-199a-5p on the protein expression of HIF-1α. Results: LUCAT1 was significantly up-regulated in ccRCC tissues and cell lines (all P<0.01), and its knockdown significantly inhibited the proliferation and migration of 786-O cells (all P<0.01). miR-199a-5p was low-expressed in ccRCC tissues and cell lines (all P<0.01), StarBase analysis showed that LUCAT1 contained a conserved target site for miR-199a-5p. miR-199a-5p exerted significant suppression on the luciferase activity of LUCAT1-Wt (P<0.01), and LUCAT1 knockdown significantly reduced miR-199a-5p expression (P< 0.01). LUCAT1 was low-expressed in 786-O cells transfected with miR-199a-5p mimics, however, it was attenuated after co-transfection with LUCAT1. The mRNA and protein expressions of HIF-1α in 786-O cells transfected with miR-199a-5p mimics were up-regulated, which was then reversed by LUCAT1 over-expression (P<0.05 or P<0.01). miR-199a-5p over-expression suppressed the proliferation and migration of 786-O cells, which was partially attenuated by LUCAT1 transfection (P<0.05 or P<0.01). Conclusion: LUCAT1 exerts oncogenic function in ccRCC via regulating miR-199a-5p/HIF-1α axis.·
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Resumen: La incidencia de carcinoma renal de células claras representa cerca de 2% de todas las neoplasias malignas. La tríada clásica de hematuria, dolor abdominal y masa palpable se estima en 10% de los casos. Stauffer describió en 1961 el primer caso llamado síndrome de disfunción hepato-nefrogénica no metastásica, este padecimiento puede encontrarse en 3 a 20% de los casos. La afectación de las enzimas hepáticas puede estar en relación con la infiltración metastásica del hígado o, bien, por disfunción no metastásica. Es una manifestación poco frecuente en cáncer renal. Ante el hallazgo de enzimas hepáticas y fosfatasa alcalina elevadas y al descartar alteración hepática anatómica y funcional, debe sospecharse el síndrome de Stauffer, lo que puede hacer la diferencia entre que éste pase inadvertido o establecer el diagnóstico de manera oportuna. Se comunica una manifestación poco frecuente de síndrome paraneoplásico en cáncer renal de células claras.
Abstract: The incidence of clear cell renal carcinoma corresponds to about 2% of all malignant neoplasms. The classic triad of hematuria, abdominal pain and palpable mass is estimated in 10% of cases. Stauffer described in 1961 the first case called nonmetastatic hepatophrenic dysfunction syndrome, this condition can be found in 3 to 20% of cases. The involvement of liver enzymes may be related to metastatic liver infiltration or also due to non-metastatic dysfunction. It is a rare manifestation in renal cancer. Before the finding of elevated liver enzymes and alkaline phosphatase, ruling out both anatomic and functional hepatic impairment, Stauffer syndrome should be suspected, being able to make the difference between going unnoticed or being a timely finding. This paper reports a little frequent manifestation of paraneoplastic syndrome of clear cell renal carcinoma.
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Objective To investigate the predictive value of CT signs in the pathological Fuhrman grading of clear cell renal carcinoma (ccRCC).Methods The clinicopathological features and CT findings of 72 patients with ccRCC which confirmed by operation and pathology were analyzed retrospectively.According to the WHO Fuhrman grading,all patients were divided into low-grade(Fuhrman gradeⅠorⅡ)or high-grade (Fuhrman gradeⅢorⅣ).ChiG square test and t-test were used to compare the clinical data and CT findings between the two groups,including morphological features (site,whether the renal medulla invasion,morphology,growth pattern,border,pseudo-envelope,lobulation sign,interface,perirenal fascia and the same lateral adrenal invasion,renal sinus and perirenal fat invasion,venous invasion,lymphadenopathy, maximum diameter),density (bleeding,necrosis ratio,calcification,fat)and enhancement characteristics (the degree of enhancement, strengthening method).And the pathological Fuhrman grading was the gold standard.The ROC was used to analyze the diagnostic efficacy of CT signs on Fuhrman grading.The Delong test was used to compare the AUC of different CT signs.Results There were significant differences in tumor maximum diameter,the renal medulla invasion,and lobulation sign between the Fuhrman low-grade and high-grade group(χ2/t＝－4.31 7,9.794,7.325,P＜0.05).There were no differences in gender,age,location sign,morphology,growth pattern, border,pseudo-envelope,interface,perirenal fascia and ipsilateral adrenal invasion,renal sinus and perirenal fat invasion,necrosis ratio,degree of enhancement,strengthening method between two groups (P＞0.05). The largest diameter of the tumor,the renal medulla invasion and the lobulation sign were useful for Fuhrman diagnosis.The AUC was 0.778,0.647 and 0.644,respectively.And there were significant differences between the maximum diameter and the renal medulla invasion or lobulation sign (P＜0.05).Conclusion The maximum diameter,medulla and lobular sign can predict the Fuhrman grading of ccRCC,and the maximum diameter prediction is the most accurate.
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Objective To investigate the CT features of clear cell renal carcinoma (ccRCC)and angiomyolipoma with minimal fat (AMLmf)and to improve the CT diagnostic accuracy of these two diseases.Methods The CT features of 55 patients with pathologically-confirmed ccRCC and 1 2 patients with pathologically-confirmed AMLmf were analyzed retrospectively,including the CT value in both plain and tri-phase enhanced CT scan,tumor enhancement rate(△R1,△R2,△R3),maximum diameter,enhanced homogeneity,location of the main tumor,cortex raising signs,etc.The statistical analysis was carried on.Results The maximum diameter,the CT value in parenchymal phase,enhancement rate (△R1,△R2,△R3)of tumors in ccRCC group were significantly higher than those of tumors in AMLmf group,and the CT value in plain CT scan in ccRCC group was significantly lower than that in AMLmf group (all P<0.05).No statistically significant difference was found in the CT value of the tumor in corticomedullary phase and in excretion phase (both P>0.05).The rate of extrarenally-located main tumors of AMLmf group was significantly higher than that of ccRCC group (P=0.020),the location of main tumors and cortex raising signs showed no statistically significant difference with the maximum tumor diameter(both P>0.05).The enhanced homogeneity of the tumor in corticomedullary phase,parenchymal phase and excretion phase in ccRCC group was lower than that in AMLmf group (all P<0.05).Conclusion The CT value in plain CT scan in ccRCC group is lower than that in AMLmf group;the enhancement rate of the ccRCC group is higher than that of the AMLmf group;the enhanced homogeneity of the ccRCC group is worse than that of the AMLmf group.The extrarenally-located main tumors are more commonly seen in AMLmf than in ccRCC,and the cortex raising signs and the location of main tumors are unrelated to the size of the tumor.
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Objective To explore the value of dual-source CT spectrum energy curve and iodine quantification in determining the degree of differentiation of clear cell renal carcinoma(ccRCC).Methods The radiographic data of 38 cases with pathologically confirmed ccRCC were analyzed retrospectively.All patients underwent dual-source CT,cortical phase and nephrographic phase dual energy scan,including 22 well-moderated differentiated(gradeⅠ,gradeⅡ)and 16 poorly differentiated neoplasms(gradeⅢ,gradeⅣ).The slope of spectrum energy curve (40-70 keV,70-100 keV,100-140 keV)and the normalized iodine concentration (NIC)between the two grades were compared. Results In the spectrum energy curve 40-70 keV and 70-100 keV segment interval,the slope of spectrum of well-moderated differentiated group was higher than that of poorly differentiated group,the difference was statistically significant(P<0.05).In the 100-140 keV segment interval,the slope of spectrum of well-moderated differentiated group was higher than that of poorly differentiated group, but the difference was insignificant(P>0.05).The NIC of well-moderated differentiated group was significantly higher than that of poorly differentiated group(P<0.05).Conclusion The slope of spectrum energy curve and NIC are correlated with the differentiation degree of ccRCC.The slope of spectrum energy curve and iodine quantification of dual-source CT could be used as new methods for preoperative grading of ccRCC.
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Objective To explore the imaging diagnosis in pancreatic metastasis from clear cell renal carcinoma. Methods Twenty three patients with pancreatic metastasis from clear cell renal carcinoma confirmed by pathology were enrolled during 2007 to 2014,and their clinical sources,images and pathologic findings were reviewed. Twenty three patients underwent CT and 8 patients underwent MRI examinations. Metastatic neoplasm in pancreas were found after nephrectomy from 3 years to 17 years (average 9 years), including17 patients were diagnosed in more than 5 years after nephrectomy. Imaging features were observed.Result Metastatic neoplasms were solitary in 5 patients and multiple in 18 patients. The diameters were from 0.2 to 5.0 cm.CT plain scan demonstrated iso-density or slight hypo-density tumors with clear boundary, without calcification, and significant enhancement. MR demonstrated significantly lower signal on T1WI and high or slightly high signal on T2WI in all metastases.After contrast injection,the metastases were enhanced significantly.In 4 cases,the obstruction of the main pancreatic duct was found. Conclusions Pancreatic metastasis from clear cell renal carcinoma mostly were found in more than 5 years after nephrectomy. The images demonstrated that single or multiple tumors with clear boundary and significant enhancement in pancreas.Medical history is the key to imaging diagnosis.
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Objective To analyze the correlation between ultrasonographic features and pathological grade of clear cell renal carcinoma(CCRCC). Methods We retrospectively analyzed the conventional ultrasound and contrast enhanced ultrasound in 150 cases of CCRCC from November 2013 to February 2017 which were confirmed by pathology in Institute of Nephrology of Nanjing Gener-al Hospital .Pathological grade was classified into Ⅰ , Ⅱ, Ⅲ,Ⅳ, with 122 cases of low grade CCRCC (grade Ⅰ and grade Ⅱ) and 28 cases of high grade CCRCC ( grade Ⅲ and grade Ⅳ ) .Their correlations with the features of conventional ultrasound and contrast en-hanced ultrasound were analyzed . Results The maximum diameter of the tumor ( low grade:40.00 ±16.11, high grade:56.43 ± 23.30), the minimum diameter of the tumor(low grade:34.73±14.02,high grade:45.79±16.17), rate of pseudocapsule displaying [low grade:presence52(74%),absence70(26%);high grade:presence4(14%),absence24(86%)], and the enhanced uniformity [low grade:uniformity 19(16%),Cystic change 95(78%),necrosis 8(6%);high grade:uniformity 5(18%),Cystic change 1(4%), necrosis 22( 78%) ] were related to the pathological grade .Binary logistic regression analysis showed that the main factors related to the pathological grade were the rate of pseudocapsule displaying (OR:4.348,95%CI: 1.252-15.096)and the enhanced uniformity (OR:11.425,95%CI:4.326-29.229) Conclusion The characteristics of CCRCC conventional ultrasound and contrast-enhanced ultra-sound were related to the pathological grade , and the main factors were the rate of pseudocapsule displaying and enhanced uniformity .
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Objective To analyze the correlation between ultrasonographic features and pathological grade of clear cell renal carcinoma(CCRCC). Methods We retrospectively analyzed the conventional ultrasound and contrast enhanced ultrasound in 150 cases of CCRCC from November 2013 to February 2017 which were confirmed by pathology in Institute of Nephrology of Nanjing Gener-al Hospital .Pathological grade was classified into Ⅰ , Ⅱ, Ⅲ,Ⅳ, with 122 cases of low grade CCRCC (grade Ⅰ and grade Ⅱ) and 28 cases of high grade CCRCC ( grade Ⅲ and grade Ⅳ ) .Their correlations with the features of conventional ultrasound and contrast en-hanced ultrasound were analyzed . Results The maximum diameter of the tumor ( low grade:40.00 ±16.11, high grade:56.43 ± 23.30), the minimum diameter of the tumor(low grade:34.73±14.02,high grade:45.79±16.17), rate of pseudocapsule displaying [low grade:presence52(74%),absence70(26%);high grade:presence4(14%),absence24(86%)], and the enhanced uniformity [low grade:uniformity 19(16%),Cystic change 95(78%),necrosis 8(6%);high grade:uniformity 5(18%),Cystic change 1(4%), necrosis 22( 78%) ] were related to the pathological grade .Binary logistic regression analysis showed that the main factors related to the pathological grade were the rate of pseudocapsule displaying (OR:4.348,95%CI: 1.252-15.096)and the enhanced uniformity (OR:11.425,95%CI:4.326-29.229) Conclusion The characteristics of CCRCC conventional ultrasound and contrast-enhanced ultra-sound were related to the pathological grade , and the main factors were the rate of pseudocapsule displaying and enhanced uniformity .
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PURPOSE: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expression of IR and its prognostic significance in clear cell RCC (CCRCC). MATERIALS AND METHODS: Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival. RESULTS: IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn't significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies. CONCLUSION: IR expression in CCRCC may be associated with favorable prognostic factors.
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Aged , Female , Humans , Male , Middle Aged , Blotting, Western , Carcinoma, Renal Cell/metabolism , Immunohistochemistry , Prognosis , Receptor, Insulin/metabolismABSTRACT
PURPOSE: Both insulin and insulin-like growth factor (IGF)-1 signaling are key regulators of energy metabolism, cellular growth, proliferation, and survival. The IGF-1 receptor (IGF-1R) is overexpressed in most types of human cancers including renal cell carcinoma (RCC) with poor prognosis. Insulin receptor (IR) shares downstream effectors with IGF-1R; however, the expression and function of IR in the tumorigenesis of renal cancer remains elusive. Therefore, we examined the expression of IR and its prognostic significance in clear cell RCC (CCRCC). MATERIALS AND METHODS: Immunohistochemical staining for IR was performed on 126 formalin-fixed paraffin-embedded CCRCC tissue samples. Eight of these cases were utilized for western blot analysis. The results were compared with various clinico-pathologic parameters of CCRCC and patient survival. RESULTS: IR was expressed in the nuclei of CCRCC tumor cells in 109 cases (87.9%). Higher IR expression was significantly correlated with the presence of cystic change, lower Fuhrman nuclear grade, lower pathologic T stage, and lower TNM stage, although it wasn't significantly related to diabetes status and patient survival. Western blot analyses supported the results of the immunohistochemistry studies. CONCLUSION: IR expression in CCRCC may be associated with favorable prognostic factors.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Blotting, Western , Carcinoma, Renal Cell/metabolism , Immunohistochemistry , Prognosis , Receptor, Insulin/metabolismABSTRACT
Objective To investigate the expression of Netrin-1 protein in human renal clear cell carcinoma (RCCC) and the relationships between Netrin-1,pathology and prognosis.Methods Fortyeight cases of RCCC and their adjacent tissues were selected for study,including 26 males and 22 females.The median age was 62 years (range,26 to 83 years).All 48 patients were onset for the first time,confirmed by pathology.All cases had no radiotherapy,chemotherapy or biological treatment before operation.Fuhrman grade:6 cases in grade Ⅰ,6 cases,in grade Ⅱ,27 cases in grade Ⅲ and 9 cases in grade Ⅳ.The AJCC staging in 2010:20 cases in stage Ⅰ-Ⅱ],28 cases in stage Ⅲ-Ⅳ.The expression of Netrin-1 protein was detected by immunohistochemical staining and its clinical significance was analyzed.All cases were followed up for more than 5 years.Survival analysis lines were made by Kaplan-Meier method and the difference between groups was tested by the Log-rank test.Results The expression of Netrin-1 protein was higher in renal cancers [71％ (34/48)] than that in the adjacent normal tissues [17％ (8/48)] (P＜0.05).Netrin-1 protein expression rates were 42％(5/12) in Fuhrman Ⅰ-Ⅱ tumors and 81％ (29/36) in Fuhrman Ⅲ-Ⅳ tumors,while 55％ (11/20) in stage Ⅰ-Ⅱ and 82％ (23/28) in stage Ⅲ-Ⅳ,respectively (P＜0.05).The 5-year survival rate in high protein expression group and in low protein expression group was 62％ (21/ 34) and 79％ (11/14).The survival curve had different trend,with no significant difference between groups (P＞0.05).Conclusions Netrin-1 protein plays an important role in the development of RCCC.It might be a new specific tumor marker of RCCC,and might become a new target in treatment of RCCC.
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Objective To study the expression of carbonic anhydrase 9(CA9) in clear cell renal carcinoma(ccRCC), and the relationship between the expression and recurrence .Methods Paraffin-embedded tissues from 53 ccRCC cases were collected during the past 3 years,and immunohistochemistry was used to detect the expression of CA 9.Fifty-three cases were followed up to evaluate the disease-free survival ( DFS) and recurrence .Association of CA9 expression with recurrence was then analyzed .Results Localized RCC recurred in eleven cases , the median DFS was 10 months, the integral optical density ( IOD) of the recurrent cases was 230 879 .84 ±64 878 .72 while the IOD of the thirteen nonrecurrent cases was much higher,444 993.31 ±146 946.27(P<0.01).Conclusion There might be a positive correlation between the low expression of CA9 and the recurrence of ccRCC .CA9 may help predict the ccRCC patients ’ prognosis.
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Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new method of sampling mediastinal lymph nodes to aid in diagnosing lymphadenopathy and in staging metastatic cancers. This paper describes a case of renal cell carcinoma with mediastinal and hilar lymph nodes metastasis that was diagnosed using EBUS-TBNA. A 17-year-old woman who had mediastinal lymphadenopathy and a right renal mass underwent imaging studies. The results of a first EBUS-TBNA suggested malignancy, but the type of tumor and exact site of the primary tumor were uncertain. Therefore, we repeated EBUS-TBNA with a lower pressure on the vacuum syringe. We successfully diagnosed the mediastinal lymph node metastasis from renal cell carcinoma.
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Adolescent , Female , Humans , Biopsy, Needle , Carcinoma, Renal Cell , Lymph Nodes , Lymphatic Diseases , Needles , Neoplasm Metastasis , Syringes , VacuumABSTRACT
We report a case of tuberous sclerosis associated with two histologically different renal cell carcinomas (RCCs) and multiple angiomyolipomas (AMLs) in the same kidney. A 43-year-old female was admitted to our hospital with left flank pain and a huge palpable mass in the left flank area. Abdominal computed tomography revealed two concurrent RCCs and multiple AMLs in the left kidney. Because of the clinical suspicion of RCC, the patient underwent left radical nephrectomy. On gross examination, the total size of the resected left kidney was 30.5x17x8 cm. Microscopically, the upper pole tumor features were consistent with chromophobe RCC and the midpole tumor was a clear-cell RCC. The multifocal masses in the remaining remnant parenchyma were AMLs. Six months after surgery, the patient is healthy without signs of tumor recurrence.
Subject(s)
Adult , Female , Humans , Angiomyolipoma , Carcinoma, Renal Cell , Flank Pain , Kidney , Nephrectomy , Recurrence , Tuberous SclerosisABSTRACT
PURPOSE: Caveolin-1 is proposed to represent a novel tumor suppressor protein and expression of recombinant caveolin-1 is sufficient to restrict the growth potential of transformed cells isolated from primary tumors of the breast, lung, and ovaries. We examined the relationship of caveolin-1 and Ki-67 expression to clinicopathological variables in patients with clear cell carcinomas of the kidney. MATERIALS AND METHODS: We examined caveolin-1 and Ki-67 expression in 119 clear cell carcinomas of the kidney using immunohistochemistry, and analyzed its relationship with tumor size, nuclear grade, TNM stage, vascular invasion, capsular invasion, metastasis, and metachronous metastasis were investigated. RESULTS: Of the 119 tumors analyzed, lymph node and distant metastasis (synchronous metastasis: 7, metachronous metastasis: 15) occurred in 3 and 22 cases, respectively. Caveolin-1 expression correlated with the T stage(p=0.004), TNM stage(p=0.013), metastasis(p=0.013), and metachronous metastasis(p=0.001). Ki-67 expression correlated with the T stage(p=0.041), nuclear grade(p=0.011), and vascular invasion(p=0.043). Caveolin-1 and Ki-67 expression showed similar changes, but there was no statistical significance(p=0.050). CONCLUSIONS: Caveolin-1 is expressed frequently in patients with metachronous metastasis, and may predict metastasis after surgery for clear cell carcinoma of the kidney.