Metastasis Of Renal Cell Carcinoma Research Articles

METASTATIC RENAL CELL CARCINOMA TO THE ORAL CAVITY: AN UNUSUAL CASE

Renal cell carcinoma (RCC) metastasis to the oral cavity is relatively rare. The oral manifestation of RCC is related to high rates of morbidity and worsening of the clinical prognosis. A 61-year-old male patient with a previous diagnosis of renal cancer was referred to the dental service with a complaint of nodular lesion in the oral cavity. On intraoral examination, an extensive nodular lesion on the gingiva associated with the upper molars was noted. After biopsy, the microscopic examination revealed nests of polygonal cells partitioned by fibrovascular septa in an alveolar arrangement. Immunohistochemical analysis showed positivity for AE1/AE3, PAX8, CD10, and vimentin markers. Tumor cells were negative for CD34 and CD163. The diagnosis of oral metastasis of RCC was made. The patient has been treated with chemotherapy and care monitoring by a multidisciplinary team.

SP2.2.1 Surgical Resection of metastases to the adrenal gland

Abstract Aims The adrenal gland is a common metastatic site for lung, breast, skin, renal, thyroid, and colorectal cancers. Our aim was to review resection of adrenal metastases and their primary pathology and the impact of adrenalectomy on the survival and disease free survival rate. Methods Retrospective review of adrenalectomy for adrenal metastases in a single regional centre between June 2010–2020. Results 34 adrenalectomies in 33 patients were performed. Median age of patients was 70 (39–82). All adrenal lesions were diagnosed on staging or surveillance CT scan. Isolated adrenal metastases were seen in 26 patients. The most common primary malignancy was renal cell carcinoma (RCC) (n=20), followed by non small cell lung cancer (NSCLC) (n=6), colorectal adenocarcinoma (n=2) and infiltrating ductal breast carcinoma (n=2). Other primaries include malignant melanoma, oesophageal adenocarcinoma, prostate adenocarcinoma and hepatocellular carcinoma (each n=1). Adrenalectomy was carried out for diagnosis in 5 cases, 4 where no resection of the primary lesion was performed. Median time from resection of primary lesion was 4 years (1–16). 5 patients had synchronous adrenal metastases, 1 with synchronous resection of primary. At the time of writing, there was a 38% mortality. 84% of deaths were due to disease progression. Median survival from adrenalectomy was 23 months (4–52 months). Of the surviving patients 76% are disease free and under oncological or clinical surveillance. 24% underwent further systemic or localised oncological therapy. Conclusions Survival rate following adrenalectomy for metastatic deposits is 62%. Better outcomes are observed in patients with RCC metastases.

Pan-keratin Immunostaining in Human Tumors: A Tissue Microarray Study of 15,940 Tumors.

To evaluate the efficiency of pan-keratin immunostaining, tissue microarrays of 13,501 tumor samples from 121 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, strong pan-keratin immunostaining was seen in epithelial cells. Staining intensity was lower in hepatocytes, islets of Langerhans, and pneumocytes but markedly reduced in the adrenal cortex. Pan-keratin was positive in ≥98% of samples in 62 (83%) of 75 epithelial tumor entities, including almost all adenocarcinomas, squamous cell and urothelial carcinomas. Only 17 of 121 tumor entities (13%) had a pan-keratin positivity rate between 25% and 98%, including tumors with mixed differentiation, endocrine/neuroendocrine tumors, renal cell carcinomas, adrenocortical tumors, and particularly poorly differentiated carcinoma subtypes. The 15 entities with pan-keratin positivity in 0.9%-25% were mostly of mesenchymal origin. Reduced/absent pan-keratin immunostaining was associated with high UICC stage (p = 0.0001), high Thoenes grade (p = 0.0183), high Fuhrman grade (p = 0.0049), advanced tumor stage (p < 0.0001) and lymph node metastasis (p = 0.0114) in clear cell renal cell carcinoma, advanced pT stage (p = 0.0007) in papillary renal cell carcinoma, and with advanced stage (p = 0.0023), high grade (p = 0.0005) as well as loss of ER and PR expression (each p < 0.0001) in invasive breast carcinoma of no special type (NST). In summary, pan-keratin can consistently be detected in the vast majority of epithelial tumors, although pan-keratin can be negative a fraction of renal cell, adrenocortical and neuroendocrine neoplasms. The data also link reduced pan-keratin immunostaining to unfavorable tumor phenotype in in epithelial neoplasms.

A Case Report of Acute Adrenal Insufficiency after Subtotal Stomach-Preserving Pancreaticoduodenectomy for Pancreatic Metastasis of Renal Cell Carcinoma

A Case Report of Acute Adrenal Insufficiency after Subtotal Stomach-Preserving Pancreaticoduodenectomy for Pancreatic Metastasis of Renal Cell Carcinoma

Nomogram to predict risk and prognosis of synchronous lung metastasis in renal cell carcinoma: A large cohort analysis.

We aimed to construct and validate nomogram models that predict the incidence of lung metastasis (LM) in patients with renal cell carcinoma (RCC) and evaluate overall survival (OS) and cancer-specific survival (CSS) among RCC patients with LM.The Surveillance, Epidemiology, and End Results database was analyzed for RCC patients diagnosed between 2010 and 2015. The X-tile program was used to determine the best cutoff values for age at initial diagnosis and tumor size. Logistic regression analysis was performed to explore independent risk factors for LM, and COX regression analysis was used to identify prognostic indicators for OS and CSS in lung metastatic RCC patients. Subsequently, 3 nomograms were established, and receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were utilized to validate their accuracy.We randomly assigned 10,929 patients with RCC to 2 groups with 1:1 allocation. Multivariate logistic analyses revealed that pathology, tumor (T) stage, nodes (N) stage, race, grade, surgery, metastatic sites, and tumor size were independent risk factors for LM. Multivariate Cox analyses showed that pathology, T stage, N stage, age, surgery, metastatic sites, and residence were independent prognostic factors for OS and CSS in patients with LM. Then, nomograms were developed based on the multivariate logistic and Cox regression analyses results. The ROC and DCA curves confirmed that these nomograms achieved satisfactory discriminative power.Three effective nomograms were constructed and validated that can be used to assist clinicians in predicting the incidence of LM and evaluating the prognosis of lung metastatic RCC.

SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin

Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin β3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis.

Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA.

BackgroundClear cell renal cell carcinoma (ccRCC) is a common malignant tumour of the urinary tract. The major causes of poor prognosis are the lack of early diagnosis and metastasis. Accumulating research reveals that circular RNAs (circRNAs) can play key roles in the development and the progression of cancer. However, the role of circRNAs in ccRCC is still uncertain.MethodsThe circRNAs microarray (n = 4) was performed to investigate the circRNAs with differential expression in ccRCC tissues. The candidate circRNA was selected based on the cut‐off criteria, such as circRNA expression abundance, circRNA size and the design of divergent primers. The circ‐transportin‐3 (TNPO3) levels in ccRCC tissues were tested by quantitative real‐time (qRT)‐PCR (n = 110). The characteristics and subcellular localization of circ‐TNPO3 were identified via RNase R assay, qRT‐PCR and fluorescence in situ hybridization (FISH). Then, we explored the biological roles of circ‐TNPO3 in ccRCC via the function experiments in vitro and in vivo. RNA pull‐down, RNA immunoprecipitation, bioinformatic analysis, RNA‐FISH assays and rescue assays were applied to validate the interactions between circ‐TNPO3, insulin‐like growth factor 2 mRNA‐binding protein 2 (IGF2BP2) and serpin family H member 1 (SERPINH1) to uncover the underlying molecular mechanisms of circ‐TNPO3.ResultsWe detected the obvious downregulation of circ‐TNPO3 in ccRCC compared to matched adjacent normal tissues (n = 110). The lower circ‐TNPO3 expression was found in ccRCC patients with distant metastasis, higher World Health Organization/International Society of Urologic Pathologists (WHO/ISUP) grade and more advanced tumour T stage. In vitro and in vivo, circ‐TNPO3 significantly suppressed the proliferation and migration of ccRCC cells. Mechanistically, we elucidated that circ‐TNPO3 directly bound to IGF2BP2 protein and then destabilized SERPINH1 mRNA. Moreover, IGF2BP2/SERPINH1 axis was responsible for circ‐TNPO3's function of inhibiting ccRCC metastasis. Epithelial splicing regulatory protein 1 (ESRP1) was probably involved in the biogenesis of circ‐TNPO3.ConclusionsCirc‐TNPO3 can suppress ccRCC progression and metastasis via directly binding to IGF2BP2 protein and destabilizing SERPINH1 mRNA. Circ‐TNPO3 may act as a potential target for ccRCC treatment.

Incidence of Metastatic Renal Cell Carcinoma in Sulaimaniyah Government, Iraq

Renal cell carcinoma (RCC) has a well-known tendency to metastasize. Kidney Cancer (KC) has some histopathological subtypes; the most common one is clear cell renal cell carcinoma (ccRCC), which can spread to distant organs in the body like the lungs, brain, bone, and lymphatic system. Multiple RCC metastasis can be treated by complete surgical resection of all metastases if the patient is amenable for surgery, in spite that there is another option in the management of (metRCC) like chemotherapy, radiotherapy and immunotherapy. Full metastasectomy was related to a significant extension of median cancer-specific survival. Also, it is important during multiple metastasectomies; the surgical beds have free of tumours. Primary systemic therapy is targeted therapy (TT) that affect the vascular endothelial growth factor pathway, which improves progression-free survival and overall survival. The results of this study demonstrate that the incidence of metastasized RCC was 0.28 in 2017, which increased until in 2018, it became 0.92, which was the first pick. The second pick was in 2019, which was 1.26. After that, the incidence steadily decreased till 2020 and became 0.57 per 100,000 populations. Regarding types of operation and laterality, partial nephrectomy was done for (45%), radical nephrectomy for 52.5% and 2.5% were non operated, and (64.8%) of the primary tumour was right-sided, and 35.2% was left-sided. Regarding male gender 75 (61.5%) and female 47 (38.5%), non-symptomatic patients were 57.4% while 28.7% had flank pain history, 7.4% had gross hematuria, and 4.1% had back pain symptoms. Route of diagnosis only by ultrasound (US) in 86% and least diagnostic tool is magnetic resonance image (MRI) (0.8%). The most frequent (72.7%) histologic subtype was ccRCC. The most frequent site of distant metastasis was a respiratory system which was 9.8%, then 4.9% metastasized to the skeletal system. In contrast, connective tissue, the endocrine system, and the digestive system had the least common site (0.8%), 10.7% had metachronous, and 13.9% had synchronous metastasis, respectively. Regarding risk factors, 83.4% had a smoking history, the mean body mass index (BMI) was 27.3 kg/m2 , and 46.7% had ahypertension history. This study demonstrated the incidence of MetRCC in the Sulaimaniyah government. Finally, we concluded that the incidence of metastatic RCC increases annually, also synchronous metastasis has higher than metachronous metastasis. In contrast, metastatic RCC is more common in males than females, and most cases of RCC are diagnosed incidentally by a noninvasive imaging method, which was US.

Integrated bioinformatics analysis to identify the key gene associated with metastatic clear cell renal cell carcinoma.

Metastasis of clear cell renal cell carcinoma (ccRCC) is a leading cause of death. The purpose of this research was to investigate the key gene in ccRCC tumor metastasis. Three microarray datasets (GSE22541, GSE85258, and GSE105261), which included primary and metastatic ccRCC tissues, were obtained from the Gene Expression Omnibus (GEO) database. Expression profiling and clinical data of ccRCC were downloaded from The Cancer Genome Atlas (TCGA) dataset. A total of 20 overlapping differentially expressed genes (DEGs) were identified using the R limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the DEGs were mainly enriched in tumor metastasis-related pathways. Gene expression analysis and survival analysis in the GEPIA2 database further identified the key gene HSD11B2. qRT-PCR result manifested that HSD11B2 level was significantly down-regulated in ccRCC tissues compared with adjacent normal tissues. ROC analysis showed that HSD11B2 exhibited good diagnostic efficiency for metastatic and non-metastatic ccRCC. Univariate and multivariate Cox regression analysis showed that HSD11B2 expression was an independent prognostic factor. To establish a nomogram combining HSD11B2 expression and clinical factors, and a new method for predicting the survival probability of ccRCC patients. Gene Set Enrichment Analysis (GSEA) enrichment results showed that low expression of HSD11B2 was mainly enriched in tumor signaling pathways and immune-related pathways. Immune analysis revealed a significant correlation between HSD11B2 and tumor immune infiltrates in ccRCC. This study suggests that HSD11B2 can serve as a potential biomarker and therapeutic target for ccRCC metastasis.

LINC00174 promotes cell proliferation and metastasis in renal clear cell carcinoma by regulating miR-612/FOXM1 axis

Background Kidney renal clear cell carcinoma (KIRC) is the most common pathological subtype of kidney tumor. Reportedly, LINC00174 is a key regulator in cancer progression. This study aims to clarify the role and molecular mechanism of LINC00174 in the progression of KIRC. Methods LINC00174 expression in KIRC and its prognostic value were analyzed by bioinformatics. LINC00174, miR-612 and FOXM1 mRNA expression levels in KIRC clinical samples and cell lines were detected by qRT-PCR. After LINC00174 was overexpressed or knocked down, CCK-8, BrdU and Transwell assays were adopted to evaluate the proliferation and metastatic potential of KIRC cells. Bioinformatics and dual luciferase reporter assays were employed to validate the targeting relationship between miR-612 and LINC00174 or FOXM1 mRNA, respectively. Western blot assay was performed to detect FOXM1 protein expression in KIRC cells. Results LINC00174 expression and FOXM1 expression were up-regulated in 42 cases of KIRC tissues (p < 0.001), while miR-612 expression was down-regulated (p < .001). LINC00174 overexpression or miR-612 inhibitor promoted the viability and proliferation of KIRC cells (p < .01). Migration and invasion of KIRC cells were promoted when the cells were transfected with LINC00174 overexpression or miR-612 inhibitor (p < .05). LINC00174 can competitively bind with miR-612 to repress the expression of miR-612, in turn up-regulate the expression of FOXM1 mRNA. Conclusion LINC00174 facilitates the proliferation and metastatic potential of KIRC cells via regulating the miR-612/FOXM1 axis.

Comprehensive analysis of lower mitochondrial complex I expression is associated with cell metastasis of clear cell renal cell carcinoma.

BackgroundClear cell renal cell carcinoma (ccRCC) is characterized by high metastasis potential. It is of great importance to explore the mechanisms underlying ccRCC metastasis and to enable development of potent therapeutics. The mitochondrial complex I (CI) had been considered to play an important role in the development of cancers, but less known in ccRCC.MethodsWe utilized available public databases of ccRCC, including single-cell RNA sequencing (scRNA-seq) data GSE73121 and The Cancer Genome Atlas-kidney renal clear cell carcinoma (TCGA-KIRC). Principal component analysis (PCA) and t-Distributed Stochastic Neighbor Embedding (tSNE) analysis were evaluated the heterogeneity of metastatic renal cell carcinoma (mRCC) and primary renal cell carcinoma (pRCC). Protein-protein interaction (PPI) network identified critical gene. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) performed to explore the potential biologic pathways.ResultsOur study revealed a significant gene expression heterogeneity between pRCC and mRCC. A PPI network based on differentially expressed genes (DEGs) identified electron transport chain (ETC), especially mitochondrial CI, as the key network hub. Further analysis revealed that the role of mitochondrial CI is associated with tumor metastasis and immune responds of ccRCC. Although CI had low frequency mutations in ccRCC, CI expression is associated with the high frequency mutated genes. A prognosis model included 7 CI genes, and these had a significant effect on overall survival (OS). The area under the curve at 1, 3, and 5 years was 0.717, 0.685, and 0.728, respectively. Transcription factor analysis predicted that PPARG possibly is a potential transcription activator of CI genes in ccRCC.ConclusionsOverall, we found that CI expression is associated with ccRCC progress. CI and PPARG may be potential biomarkers for metastatic ccRCC.

Combined interdisciplinary treatment of metastatic bone lesions – embolization, biopsy, ablation, and surgery in one operative sitting

Abstract Objective As a result of modern cancer treatment and thereby improved survival, many cancers spread to bone. Bone metastases may cause immobilizing pain and increase the risk of fracture even by inadequate or no trauma. Treatment of these patients should promptly address confirmation of the tumor entity, local control as well as adequate and lasting surgical stabilisation of the affected bone or joint. We present a setup to perform all the above in a single operative sitting. Methods Required imaging is completed before initial consultation. The treatment plan is discussed in an interdisciplinary team according to the primary tumor and thereof resulting survival estimation, the imaging evaluation and patient's expectations and needs. In a single operative setup, the patients are treated by an interventional radiologist and an orthopaedic surgeon in a hybrid operating room. Thus, in one single setup the patient may undergo arteriogram to diagnose hypervascularity of the tumor followed by embolization if needed, CT-guided biopsy, percutaneous radiofrequency or cryotherapy ablation of the metastases for local tumor control and eventually surgical treatment with resection of the tumor, joint replacement or minimally-invasive stabilization as needed. Biopsy results may be discussed at inhouse tumor boards and adjuvant radio- or chemotherapy may be planned for the postoperative course. Results Five combined procedures were performed in 5 patients (3 female, 2 male patients; median age 65 years (range 61–77)) each in one single operative sitting since October 2021. Three patients suffered from metastases of renal cell carcinoma, one each from thyroid carcinoma and breast cancer respectively. Metastases were located in the femoral meta- and diaphysis in 3 cases and in the acetabulum in 2 cases. Median duration of this multidisciplinary intervention was 375 min (251–426). Median length of hospital stay was 5 days (3–10). Median time from referral to definitive treatment was 24 days (17–32). All patients were able to walk with crutches immediately after treatment. No complications occurred. Conclusion Combined multidisciplinary treatment of patients with metastatic bone disease is possible and may be favourable in respect of minimising the number of consultations, anaesthesias and interventions. This should lead to accelerated and pain-free mobilisation, thus maximising the patients’ quality of life.

Pazopanib-induced hypothyroidism in a patient with adrenal metastasis of renal cell carcinoma

Pazopanib-induced hypothyroidism in a patient with adrenal metastasis of renal cell carcinoma

Case of metachronous clear cell bladder metastasis on low risk localized renal cell carcinoma patient.

IntroductionRenal cell carcinoma (RCC) is well known for its ability to metastasize into different organs. However, the management of metachronous RCC is still not yet standardized.Case PresentationA 62 years old man was presented with haematuria for the last 2 months. CT scan revealed bladder mass with a size of 2,5 cm and underwent en-bloc resection of bladder mass. The histopathological result showed non-muscle-invasive bladder clear cell renal carcinoma. The patient had a history of left nephrectomy in 2017 and meningioma mass metastasectomy in 2020 with the same histopathological origin.ConclusionBladder metastasis of RCC can be treated by endoscopic surgical intervention.

Safety of Minimally Invasive Surgical Techniques in Large Adrenal Lesions: A Single-Centre Study.

To compare perioperative outcomes of minimally invasive surgery for ≥5 cm and <5 cm adrenal lesions. Retrospective cohort study. Hacettepe University School of Medicine, Ankara, Turkey, between October 2007 and September 2019. Data of 83 patients operated for adrenal lesions was collected retrospectively. Patients were categorized into two groups based on the size of the adrenal gland as <5 cm and ≥5 cm. The groups were compared in terms of perioperative outcomes. The median age of the patients was 51 (41-60) years, with a female-to-male ratio of 27/56. The median follow-up period was 27 (11.5-91) months. Of 83 adrenal masses, 60 (72.3%) were in the <5 cm group and 23 (27.7%) were in the ≥5 cm group. Fifteen (18.1%) patients underwent adrenalectomy for lung cancer metastasis, whereas three (3.6%) for renal cell carcinoma metastasis. The overall rate of post-operative complications was 10.8%. Post-operative complication rates were similar in each group (p=0.433). Operation time was found to be significantly higher in patients with large adrenal masses (p=0.003). Minimally invasive surgical techniques have the same perioperative results in the group with adrenal lesions ≥5 cm compared to <5 cm and may be safely employed in this group of patients. Laparoscopy, Robotic assisted laparoscopy, Adrenalectomy, Metastasectomy, Adrenal gland neoplasms.

Linc01133 promotes proliferation and metastasis of human renal cell carcinoma through sponging miR-760

ABSTRACT Renal cell carcinoma (RCC) is one of the most frequent human tumors and has brought great threats to the health of the people around the globe. It was reported that linc01133, a long non-coding RNA (lncRNA), was involved in the pathogenesis and development of several human cancer. But the biological role of linc01133 in RCC is still not understood. The present study aimed to investigate the biological functions of linc01133 in RCC. We did some biological experiments in this study, including quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, MTT assay, wound healing assay, Transwell invasion assay and xenograft tumor assay. In this study, we found the expression levels of linc01133 markedly increased in the RCC tissues compared with the normal tissues. And we found that the over-expressing of linc01133 promoted cell proliferation, migration and invasion, the interfering of linc01133 inhibited cell proliferation, migration and invasion. Furthermore, we found that the interfering of linc01133 inhibited tumor growth in murine xenograft models. Additionally, we found that linc01133 promotes RCC cell proliferation, migration and invasion through sponging miR-760. Collectively, our work preliminarily illuminated the tumor-promoting role of linc01133 in RCC and the potential molecular mechanism. Thus, our study may provide some evidence for the treatment of RCC.

RNA-seq and Mitochondrial DNA Analysis of Adrenal Gland Metastatic Tissue in a Patient with Renal Cell Carcinoma

Simple SummaryWe performed mutation analysis of ribonucleic acid sequencing (RNA-seq) and whole mitochondrial genome data from tissues collected from metastatic lesions of a male patient in his 60s with metastatic renal cell carcinoma. We confirmed the common mutation sites of a mitochondrial gene containing the T3394Y, R11,807G, and G15,438R sites. Pathway analysis, using RNA-seq data, confirmed the common mutant pathway between renal cell carcinoma and metastatic adrenal carcinoma as cytokine–cytokine receptor (CCR) interaction. However, no common nuclear gene mutations were identified. The two similar sequences suggest that mtDNA-mutation-driven metastasis to the adrenal gland may affect CCR interactions and cause cancer cells to thrive.This study aimed to clarify whether genetic mutations participate in renal cell carcinoma (RCC) metastasis to the adrenal gland (AG). Our study analyzed whole mitochondrial gene and ribonucleic acid sequencing (RNA-seq) data from a male patient in his 60s with metastatic RCC. We confirmed common mutation sites in the mitochondrial gene and carried out Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis using RNA-seq data for RCC and adrenal carcinoma. Furthermore, we confirmed the common mutation sites of mitochondrial genes in which the T3394Y (p.H30Y) site transitioned from histidine (His.; H) to tyrosine (Tyr.; Y) in the NADH dehydrogenase subunit 1 (ND1) gene. The R11,807G (p.T350A) site transitioned from threonine (Thr.; T) to alanine (Ala.; A). Additionally, the G15,438R or A (p.G231D) site transitioned from glycine (Gly.; G) to aspartic acid (Asp.; D) in cytochrome b (CYTB). Furthermore, pathway analysis, using RNA-seq, confirmed the common mutant pathway between RCC and adrenal carcinoma as cytokine–cytokine receptor (CCR) interaction. Confirmation of the original mutation sites suggests that transfer to AG may be related to the CCR interaction. Thus, during metastasis to the AG, mitochondria DNA mutation may represent the initial origin of the metastasis, followed by the likely mutation of the nuclear genes.

Scapular renal cell carcinoma metastasis as a cause of high-output heart failure: a case report

BackgroundHigh-output heart failure is a rare condition that occurs when the heart is unable to respond to a sustained increase in blood demand. On echocardiography, a cardiac index of > 4 L/min/m2 (or 6 L/min) is a clear indicator of this disorder. The causes of high-output heart failure vary, but they all involve peripheral vasodilation or arteriovenous shunting. Renal cell carcinoma is well known for producing high levels of angiogenic growth factors that induce arteriovenous shunts. The decrease in peripheral arterial resistance and the increase in venous return result in a permanent high cardiac output, followed by congestive heart failure. Single bone metastases of renal clear cell carcinoma tumours causing high cardiac output and heart failure symptoms have been reported less than ten times in the medical literature.Case presentationBefore a right-shoulder painful lump with a murmur when auscultated, magnetic resonance imaging revealed a large scapular mass, which was biopsied and found to be a bone metastasis of renal cell carcinoma. Two months later, the patient developed heart failure for the first time. There was no evidence of cardiac disease on echocardiography. The cardiac output was 9.8 L/min and the cardiac index was 5.1 L/min/m2. Doppler ultrasound revealed numerous arteriovenous shunts in the large scapular metastasis and a right axillary artery flow of 24% of cardiac output. Sustained lower cardiac output was obtained following lesion-focused radiotherapy and systemic antiangiogenic treatment with axitinib and pembrolizumab.ConclusionsHerein, we present a unique case of high-output heart failure in a 70-year-old man diagnosed by echocardiography and upper-limb Doppler ultrasound in the context of metastatic renal cell carcinoma without pre-existing cardiac disease. We stress the potentially life-threatening hemodynamic consequences of hypervascularity associated with arteriovenous shunts within a single metastatic renal cell carcinoma implant, the importance of auscultating any progressing bone mass, and the utility of non-invasive Doppler ultrasound assessment in this setting.

Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11

Clear cell renal cell carcinoma (ccRCC) is a common kidney malignancy that is characterized by poor prognosis. RNA-binding motif protein 15 (RBM15) has been identified as an oncogene in multiple tumors. Nevertheless, the function and mechanism of RBM15 in ccRCC are not clear. In this study, RBM15 was found to be upregulated in ccRCC cells and tissues. RBM15 enhanced the proliferation, clone formation, migration, invasion and epithelial-interstitial transition of ccRCC cells. Enhanced RBM15 was caused by the abundant histone 3 acetylation modification of the RBM15 promoter induced by EP300/CBP. RBM15 enhanced the stability of CXCL11 mRNA in an m6A-dependent manner. Moreover, RBM15 was found to promote macrophage infiltration and M2 polarization by promoting the secretion of CXCL11 in ccRCC cells in vitro and in vivo. Our findings highlight the function of RBM15 in ccRCC and reveal a novel identified EP300/CBP-RBM15-CXCL11 signaling axis, which promotes ccRCC progression and provides new insight into ccRCC therapy.

Tumor-to-Tumor Metastasis of Renal Cell Carcinoma to a Follicular Variant of Papillary Thyroid Carcinoma: A Case Report and Literature Review

Renal cell carcinoma (RCC) is the most common renal malignancy. It has a variable clinical course with metastasis to unusual sites occurring months to years after the initial diagnosis. However, metastasis can also be the first presentation of RCC. Although relatively uncommon, the thyroid gland is the most common location for RCC metastasis in the head and neck region. Tumor-to-tumor metastasis is an exceedingly rare occurrence. Only 10 cases were reported of RCC metastasis to primary thyroid neoplasms.We present a case of clear cell RCC metastasizing to a follicular of variant papillary thyroid carcinoma (FVPTC) 14 years after the initial diagnosis of RCC. A review of similar reported cases revealed that the most common primary thyroid recipient of tumor-to-tumor metastasis of RCC was FVPTC. The rich lymphovascular network in FVPTC compared to other thyroid tumors, which may promote the deposition of metastatic tumor cells, might explain this predilection.Careful review of the clinical and radiological findings and checking for any history of malignancy when examining thyroid nodules is important for guiding further studies. Performing a targeted panel of immunohistochemical stains for any suspicious areas is also essential for the diagnosis of such unusual cases.