Diagnosis Of Renal Cell Carcinoma Research Articles

The Predictive Value of Urinary HMGB1 Level in the Diagnosis and Prognosis of Renal Cell Carcinoma

The Predictive Value of Urinary HMGB1 Level in the Diagnosis and Prognosis of Renal Cell Carcinoma

Uncommon muscle metastatic sites of renal cell carcinoma

Introduction. Renal cell carcinoma (RCC) is the most common malignant renal tumor. It has a tendency for spreading to unusual and distant sites, such as the orbit, paranasal sinuses, thyroid gland, heart, skin, and muscles. Skeletal muscle metastases are accounting for only 0.4% of all metastatic localizations. Following CT, they may be presented in five different radiology types of lesions. The aim of our case was CT evaluation of rare skeletal muscle metastatic localizations of RCC, following the time interval of their occurrence in relation to the appearance of the primary tumor, with emphasis on metastases in the levator ani muscle, since this metastatic localization of RCC has not been recorded in the previous literature. Case outline. We present a 66-year-old man after partial nephrectomy, due to a primary diagnosis of RCC. Three years after the initial diagnosis, multiple distant metastases were verified at typical localizations, as well as rare localizations such as muscles, including levator ani. Conclusion. Advanced metastases in uncommon locations are most often accompanied by a poor prognosis, therefore the further algorithm includes monitoring the whole clinical and radiological status. Metastases in the levator ani muscle have been recorded for the first time in this report. Taking into account that this muscle has very important functions, such as supporting and raising the pelvic visceral structures, as well as having control of the flow of urine and defecation, it is of great importance to include this localization in the CT evaluation.

Anesthetic Management of a Patient with Renal Cell Carcinoma-Associated Venous Thrombosis and Massive Transfusion.

A 53-year-old male with a history of multiple deep venous thromboses (DVTs) underwent a right open radical nephrectomy with inferior vena cava (IVC) thrombectomy in the context of renal cell carcinoma (RCC)-associated venous thrombosis. Imaging and renal biopsy revealed a diagnosis of RCC with non-occlusive thrombosis of the left renal vein and occlusive thrombosis of the infrarenal IVC. The major risks of concern for the procedure included thrombus embolization from surgical manipulation and massive bleeding. Intraoperatively, the patient experienced significant hemorrhage requiring massive transfusion protocol. The purpose of this case report is to emphasize the importance of multidisciplinary involvement, intraoperative thrombus monitoring, and principles of massive transfusion in the management of similar cases.

Impact of the COVID-19 pandemic on diagnosis of renal cell carcinoma and disease stage at presentation.

Renal cell carcinoma (RCC) is often associated with significant morbidity and mortality, with overall survival contingent on multiple factors - most importantly, disease stage at diagnosis. Disruptions in healthcare delivery during the COVID-19 pandemic have resulted in various reported diagnostic and treatment delays, which have had detrimental impacts on malignancies such as RCC. Surgically managed cases of RCC at our center were identified using a retrospective chart review of all nephrectomies conducted from March 1, 2018, to February 28, 2023. Examination of disease characteristics in three time period cohorts (before, during, and following the COVID-19 pandemic) was undertaken. Timeframes were consistent with implementation and abolition of public health restrictions in the province of Newfoundland and Labrador. A total of 483 surgically managed RCC cases were identified during the study period. The median age was 65 years (interquartile range [IQR] 56-71), and 62.3% of patients were male. Demographics did not vary across timeframes. Before and during the pandemic, pathologic stage 3 (pT3) disease was reported in 38.9% and 35.4% of cases, respectively, whereas the post-pandemic period saw this presentation in 50.0% of patients. Surgical wait times increased significantly across study timeframes (p=0.003). The first year following the COVID-19 pandemic saw an 11.1% increase in patients presenting with pT3 RCC. These findings are suggestive of a clinically significant stage migration, which paired with prolonged wait times for surgery, provide critical consideration in the urgency of diagnostic and treatment decisions for RCC in the immediate future.

The Diagnosis and Treatment Approach for Oligo-Recurrent and Oligo-Progressive Renal Cell Carcinoma.

One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed "oligo-recurrent" disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as "oligo-progression", can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials.

Clinicopathological and molecular genetic characteristics of ELOC mutated renal cell carcinoma

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

Theranostic Lipid Nanoparticles for Renal Cell Carcinoma.

Renal cell carcinoma (RCC) is a common urological malignancy and represents a leading threat to healthcare. Recent years have seen a series of progresses in the early diagnosis and management of RCC. Theranostic lipid nanoparticles (LNPs) are increasingly becoming one of the focuses in this field, because of their suitability for tumor targeting and multimodal therapy. LNPs can be precisely fabricated with desirable chemical compositions and biomedical properties, which closely match the physiological characteristics and clinical needs of RCC. Herein, a comprehensive review of theranostic LNPs is presented, emphasizing the generic tool nature of LNPs in developing advanced micro-nano biomaterials. It begins with a brief overview of the compositions and formation mechanism of LNPs, followed with an introduction to kidney-targeting approaches, such as passive, active, and stimulus responsive targeting. With examples provided, a series of modification strategies for enhancing the tumor targeting and functionality of LNPs are discussed. Thereafter, research advances on applications of these LNPs for RCC including bioimaging, liquid biopsy, drug delivery, physical therapy, and gene therapy are summarized and discussed from an interdisciplinary perspective. The final part highlights the milestone achievements of translation medicine, current challenges as well as future development directions of LNPs for the diagnosis and treatment of RCC.

CircRARS synergises with IGF2BP3 to regulate RNA methylation recognition to promote tumour progression in renal cell carcinoma.

As the most prominent RNA modification, N6-methyladenosine (m6 A) participates in the regulation of tumour initiation and progression. Circular RNAs (circRNAs) also play crucial roles in ubiquitous life processes. Whether circRNAs are required for m6 A regulation in renal cell carcinoma (RCC) remains unclear. Meta-analysis and bioinformatics identified that IGF2BP3 was upregulated in RCC and indicated a worse prognosis. IGF2BP3 significantly promoted RCC progression in vitro and in vivo. Mechanistically, circRARS bound to KH1-KH2 domains of IGF2BP3 to enhance m6 A modification recognition. A 12-nt sequence (GUCUUCCAGCAA) was proven to be the IGF2BP3-binding site of circRARS. Additionally, CAPN15, CD44, HMGA2, TNRC6A and ZMIZ2 were screened to be the target genes regulated by the IGF2BP3/circRARS complex in an m6 A-dependent manner. Stabiliser proteins, including HuR, Matrin3 and pAbPC1, were recruited by circRARS, thereby increasing the mRNA stability of the forementioned five target genes. Consequently, the IGF2BP3/circRARS complex facilitated the lipid accumulation of RCC cells and promoted sunitinib resistance via target genes. circRARS synergised with IGF2BP3 to facilitate m6 A recognition, thereby promoting RCC progression. Thus, IGF2BP3 could be a potential biomarker for RCC diagnosis and prognosis and a therapeutic target.

Prognosis and Clinicopathological Characters of Adult TFEB-Altered Renal Cell Carcinoma: A Single Center Experience of 18 Cases

IntroductionTFEB-altered renal cell carcinoma (RCC) is a rare entity characterized by the rearrangement of the TFEB gene or TFEB amplified. The therapeutic implications and long-term survival of TFEB-altered RCC remain unclear, especially for metastatic cases. Materials and MethodsThe current study initially enrolled 7604 consecutive RCC patients at our center and a total of 248 patients were selected for FISH and immunohistochemistry (IHC) analysis. Eventually, eighteen TFEB-altered RCC patients were identified. We then reported the clinical, morphological, IHC, and radiological features of these cases. ResultsThe median age at initial diagnosis was 45 years, ranging from 18 years to 66 years. The majority of the TFEB-altered RCC patients were male (61.1%), with localized disease (T1-2N0M0, 77.8%). The median split TFEB fluorescent signal was 24%, ranging from 15%-80%. The morphological characteristics of TFEB-altered RCC were variable, with acinar, papillary, solid, or nest patterns. IHC and magnetic resonance imaging features of TFEB-altered RCC were nonspecific. Nine patients with localized disease received partial nephrectomy and five patients with localized disease received radical nephrectomy. During the median follow-up of 67 months, no signs of recurrence or metastasis were found in these patients. Two patients had distant metastasis and received axitinib plus PD-1 immunotherapy. One of them died at 40-month follow-up and another still alive at 88-month follow-up. ConclusionTFEB-altered RCC is an extremely rare variant, exhibited mixed morphological characteristics. The radiological feature lack specificity, resembling clear cell RCC or papillary RCC. Genetic analyses including FISH analysis is crucial in the diagnosis of TFEB-altered RCC. For localized TFEB-altered RCC, both radical nephrectomy and partial nephrectomy conferred satisfactory prognosis. For metastatic TFEB-altered RCC, immunotherapy-based drug combinations could be a promising treatment strategy.

Evaluation of a multiparametric renal CT algorithm for diagnosis of clear-cell renal cell carcinoma among small (≤ 4cm) solid renal masses.

To evaluate a recently proposed CT-based algorithm for diagnosis of clear-cell renal cell carcinoma (ccRCC) among small (≤ 4 cm) solid renal masses diagnosed by renal mass biopsy. This retrospective study included 51 small renal masses in 51 patients with renal-mass CT and biopsy between 2014 and 2021. Three radiologists independently evaluated corticomedullary phase CT for the following: heterogeneity and attenuation ratio (mass:renal cortex), which were used to inform the CT score (1-5). CT score ≥ 4 was considered positive for ccRCC. Diagnostic accuracy was calculated for each reader and overall using fixed effects logistic regression modelling. There were 51% (26/51) ccRCC and 49% (25/51) other masses. For diagnosis of ccRCC, area under curve (AUC), sensitivity, specificity, and positive predictive value (PPV) were 0.69 (95% confidence interval 0.61-0.76), 78% (68-86%), 59% (46-71%), and 67% (54-79%), respectively. CT score ≤ 2 had a negative predictive value 97% (92-99%) to exclude diagnosis of ccRCC. For diagnosis of papillary renal cell carcinoma (pRCC), CT score ≤ 2, AUC, sensitivity, specificity, and PPV were 0.89 (0.81-0.98), 81% (58-94%), 98% (93-99%), and 85% (62-97%), respectively. Pooled inter-observer agreement for CT scoring was moderate (Fleiss weighted kappa = 0.52). The CT scoring system for prediction of ccRCC was sensitive with a high negative predictive value and moderate agreement. The CT score is highly specific for diagnosis of pRCC. The CT score algorithm may help guide renal mass biopsy decisions in clinical practice, with high sensitivity to identify clear-cell tumors for biopsy to establish diagnosis and grade and high specificity to avoid biopsy in papillary tumors. • A CT score ≥ 4 had high sensitivity and negative predictive value for diagnosis of clear-cell renal cell carcinoma (RCC) among solid ≤ 4-cm renal masses. • A CT score ≤ 2 was highly specific for diagnosis of papillary RCC among solid ≤ 4-cm renal masses. • Inter-observer agreement for CT score was moderate.

The role of infliximab in treating refractory cardiac sarcoidosis

Abstract Introduction Cardiac sarcoidosis (CS) is associated with therapeutic challenges, and a high morbidity and mortality. Tumour necrosis factor alpha inhibitors like infliximab may be a treatment option for patients with persistent myocardial inflammatory activity despite conventional immunosuppressive treatment with steroids and steroid-sparing agents. Purpose To identify the safety and efficacy of infliximab in the treatment of refractory cardiac sarcoidosis. Methods We conducted a review of refractory CS patients who had been or were actively on treatment with Infliximab at our specialist tertiary care hospital from January 2017 to January 2023. Serial echocardiographic and FDG-PET scan changes as well as long term clinical data on morbidity and mortality was recorded. Results Six CS patients on infliximab were retrospectively identified. The mean age at CS diagnosis was 47.0±5.9 years and mean duration between CS diagnosis and starting infliximab was 21.4±14.2 months (Table 1). Infliximab was commenced due to persistent inflammation on FDG-PET scan and/or CMR despite being on at least two agents (prednisolone and methotrexate ± hydroxychloroquine) in 5 cases and prednisolone alone (intolerance to methotrexate) in one case. At baseline, 3 patients presented with ventricular arrhythmias, 2 with atrioventricular block and 2 with heart failure. After a mean follow up of 21.2±15.5 months of being on infliximab, 5/6 CS patients had decreased myocardial uptake on PET (1 was awaiting a scan) which included complete resolution of FDG-PET signal in one patient (Table 2). A trend in improvement of mean LVEF [52.7±6.6% to 60.2±5.9%, p = 0.10] and reduction of mean prednisolone dose [19.2±6.6mg to 11.3±7.0mg, p = 0.08] was observed during Infliximab treatment. None of the patients had worsening of LVEF or admission with acute heart failure whilst being on infliximab. A total of 4/6 patients had an Implantable Cardioverter Defibrillator device in situ at the time of Infliximab initiation. No major arrhythmias were observed during follow up. One patient died following complications of patent foramen ovale repair. There were three new cases of infection (1 pneumonia and 2 COVID-19 pneumonitis) and one case of renal cell carcinoma diagnosis three years after Infliximab treatment initiation. The drug safety was overall satisfactory since none of the patients required hospitalisation (Table 2). Case 2 patient stopped infliximab after 13 months of treatment and was found to have disease relapse seven months later. During a 20 month follow up of being on infliximab again, he demonstrated complete resolution of FDG uptake on subsequent FDG-PET scan. Conclusion This study supports the use of infliximab in refractory CS by demonstrating improvement in clinical, functional and tissue characterization parameters. However, infliximab is associated with an increased risk of infections.

Circulating inflammatory cytokines in relation to the risk of renal cell carcinoma: A gender-specific two-sample Mendelian randomization study.

Currently there is no specific molecular biomarker for the diagnosis and treatment of renal cell carcinoma (RCC). Here we performed a gender-specific two-sample Mendelian randomization analysis to systematically assess the effects of circulating cytokines on RCC. We have employed cis-quantitative trait loci as instrumental variables for the protein levels and expression of circulating cytokines. We estimated the causal effects of circulating cytokines on RCC risk in males and females with several Mendelian randomization methods. We observed a significant causal effect of Eotaxin on the increased risk of RCC in males (Odds ratio [OR] = 2.546, 95% confidence interval [CI] = 1.617-4.010, p value = 5.496 × 10-5), but not in females (OR = 1.352, 95% CI = 0.766-2.388, p value = 0.298). Besides, we also identified several cytokines as potentially associated with RCC in males including RANTES, MCP3, PDGFbb, TRAIL, and several other cytokines as potentially associated with RCC in females including sICAM and SCGFb. Our study highlighted that a higher level of circulating Eotaxin is causally associated with an increased risk of RCC in males but not in females. Further studies are needed to elucidate the exact mechanism and its potential application in the prognosis and treatment of RCC.

Biomarkers in renal cell carcinoma and their targeted therapies: a review.

Renal cell carcinoma (RCC) is one of the most life-threatening urinary malignancies displaying poor response to radiotherapy and chemotherapy. Although in the recent past there have been tremendous advancements in using targeted therapies for RCC, despite that it remains the most lethal urogenital cancer with a 5-year survival rate of roughly 76%. Timely diagnosis is still the key to prevent the progression of RCC into metastatic stages as well as to treat it. But due to the lack of definitive and specific diagnostic biomarkers for RCC and its asymptomatic nature in its early stages, it becomes very difficult to diagnose it. Reliable and distinct molecular markers can not only refine the diagnosis but also classifies the tumors into thier sub-types which can escort subsequent management and possible treatment for patients. Potential biomarkers can permit a greater degree of stratification of patients affected by RCC and help tailor novel targeted therapies. The review summarizes the most promising epigenetic [DNA methylation, microRNA (miRNA; miR), and long noncoding RNA (lncRNA)] and protein biomarkers that have been known to be specifically involved in diagnosis, cancer progression, and metastasis of RCC, thereby highlighting their utilization as non-invasive molecular markers in RCC. Also, the rationale and development of novel molecular targeted drugs and immunotherapy drugs [such as tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs)] as potential RCC therapeutics along with the proposed implication of these biomarkers in predicting response to targeted therapies will be discussed.

The microbiota and renal cell carcinoma.

Renal cell carcinoma (RCC) accounts for about 2% of cancer diagnoses and deaths worldwide. Recent studies emphasized the critical involvement of microbial populations in RCC from oncogenesis, tumor growth, and response to anticancer therapy. Microorganisms have been shown to be involved in various renal physiological and pathological processes by influencing the immune system function, metabolism of the host and pharmaceutical reactions. These findings have extended our understanding and provided more possibilities for the diagnostic or therapeutic development of microbiota, which could function as screening, prognostic, and predictive biomarkers, or be manipulated to prevent RCC progression, boost anticancer drug efficacy and lessen the side effects of therapy. This review aims to present an overview of the roles of microbiota in RCC, including pertinent mechanisms in microbiota-related carcinogenesis, the potential use of the microbiota as RCC biomarkers, and the possibility of modifying the microbiota for RCC prevention or treatment. According to these scientific findings, the clinical translation of microbiota is expected to improve the diagnosis and treatment of RCC.

Advances in the research of exosomes in renal cell carcinoma: from mechanisms to applications.

Renal cell carcinoma (RCC) is one of the most malignant urological tumors. Currently, there is a lack of molecular markers for early diagnosis of RCC. The 5-year survival rate for early-stage RCC is generally favorable; however, the prognosis takes a significant downturn when the tumor progresses to distant metastasis. Therefore, the identification of molecular markers for RCC is crucial in enhancing early diagnosis rates. Exosomes are a type of extracellular vesicle (EV) typically ranging in size from 30 nm to 150 nm, which contain RNA, DNA, proteins, lipids, etc. They can impact neighboring receptor cells through the autocrine or paracrine pathway, influence cellular communication, and regulate the local immune cells, consequently shaping the tumor immune microenvironment and closely associating with tumor development. The clinical application of exosomes as tumor markers and therapeutic targets has ignited significant interest within the research community. This review aims to provide a comprehensive summary of the advancements in exosome research within the context of RCC.

Prospective evaluation of core number of biopsy for renal tumor: are multiple cores preferable?

PurposeThis single-center, single-arm, prospective, open-label study was conducted to evaluate the optimal number of cores (single or multiple) in renal tumor biopsy.Materials and methodsForty-four biopsies of 44 tumors (mean diameter, 2.7 ± 1.0 cm; range, 1.6–5.0 cm) were included. Biopsy was performed under ultrasound or computed tomography fluoroscopy guidance using an 18-gauge cutting needle and the co-axial method. Two or more specimens were obtained, which were divided into first and subsequent specimens. “First specimen” and “all specimens” were histologically evaluated (i.e., appropriateness of specimen, histological diagnosis, subtype, and Fuhrman grade of renal cell carcinoma [RCC]) blindly and independently by two board-certified pathologists.ResultsMultiple specimens were successfully and safely obtained in all the biopsies. All tumors were histologically diagnosed; 40 malignancies included 39 RCCs and 1 solitary fibrous tumor, and 4 benign lesions included 2 angiomyolipomas, 1 oncocytoma, and 1 capillary hemangioma. In all RCCs, the subtype could be determined (32 clear cell RCCs, 4 chromophobe RCCs, and 3 papillary RCCs), and the Furman grade was determined in 38 RCCs. When only the first specimen was evaluated, 22.7% of the specimens were inappropriate for diagnosis, and 34 (77.3%) were histologically diagnosed. The diagnostic yield was significantly lower than that of all specimens (P = 0.0044). Univariate analysis revealed that smaller lesions were a significant predictor of diagnostic failure (P = 0.020).ConclusionBiopsy with multiple cores significantly improved diagnostic yield. Thus, operators should obtain multiple cores during renal tumor biopsy.

Exploring oncogenes for renal clear cell carcinoma based on G protein-coupled receptor-associated genes

G protein-coupled receptors (GPCRs) are a class of receptors on cell membranes that regulate various biological processes in cells, such as cell proliferation, differentiation, migration, apoptosis, and metabolism, by interacting with G proteins. However, the role of G protein-coupled receptors in predicting the prognosis of renal clear cell carcinoma is still unknown. The transcriptome data and clinical profiles of renal clear cell carcinoma patients, were downloaded from TCGA databases, and the validation group data were downloaded from number GSE167573, including 63 tumor samples and 14 normal samples. Single-cell RNA sequencing data were downloaded from the GEO database, No. GSE152938 and selected samples were used for GSEA enrichment analysis, WGCNA subgroup analysis, single-cell data analysis, and mutation analysis to explore the role of G protein-coupled receptor-related genes in the diagnosis and prognosis of renal clear cell carcinoma and to verify their reliability with cellular experiments. Finally, this study establishes a disease model based on G protein-coupled receptor-related genes, which may help to propose targeted therapeutic regimens in different strata of renal cell carcinoma patients.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author: Given name [Lisa Jia] Last name [Tran].It's ok!

Diagnostic miRNA Signatures in Paired Tumor, Plasma, and Urine Specimens From Renal Cell Carcinoma Patients.

The incidence of patients diagnosed with renal cell carcinoma (RCC) is increasing. There are no approved biofluid biomarkers for routine diagnosis of RCC patients. This retrospective study aims to identify cell-free microRNA (cfmiR) signatures in urine samples that can be utilized as biomarkers for early diagnosis of sporadic RCC patients. Tissue, plasma, and urine samples (n = 221) from 56 sporadic RCC patients and respective normal healthy donors were profiled for 2083 microRNAs (miRs) using the next-generation sequencing-based HTG EdgeSeq miR Whole Transcriptome Assay. DESeq2 (FC |1.2|, false discovery rate <0.05) was performed to identify differentially expressed miRs. Data from RCC tissue samples of The Cancer Genome Atlas database were used for miR validation. We found a 10-miR signature that distinguished RCC tissues from remote normal kidney tissue or benign kidney lesion samples. Additionally, we identified subtype-specific miRs (miR-122-5p, miR-210-3p, and miR-21-3p) and miRs specific for all RCC subtypes (miR-106b-3p, miR-629-5p, and miR-885-5p). We observed that miR-155-5p was associated with tumor size. Using The Cancer Genome Atlas data sets, we validated the miRs found in RCC tissue samples. In plasma or urine analysis, we found cfmiRs that were consistently and significantly upregulated in RCC tissue samples. A 15-cfmiR signature was proposed in urine samples of RCC patients, of which miR-1275 was consistently upregulated in tissue, plasma, and urine samples. This integrative study found diagnostic miRs/cfmiRs for RCC patients, which were validated using The Cancer Genome Atlas data sets. Distinctive cfmiR signatures found in urine may have clinical utility for the diagnosis of RCC.

Clear cell renal cell carcinoma cells show diffuse expression of phagocytotic markers through the identification of lysosome-rich eosinophilic granules.

Paneth cell-like granules (PCLG) in clear cell renal cell carcinomas (RCC) have previously been reported but were not found to express neuroendocrine markers. This study was to investigate if the eosinophilic granules (so called PCLG) were enlarged lysosomes. A retrospective review of 72 different renal tumors was conducted which included 42 clear cell RCC, 16 papillary RCC, 6 chromophobe RCC, 5 clear cell papillary RCC, 2 urothelial carcinomas and 1 unclassified RCC. All tumors were evaluated for the eosinophilic granules on hematoxylin and eosin-stained sections. In addition, PAS-D staining, immunohistochemical stains, and electron microscopy were performed. The eosinophilic granules were found in 19% (8 out of 42) clear cell RCC, but not in the other renal tumor types. The granules stained positively for PAS-D and were also positive for lysosomal protein markers CD68 and lysozyme. Electron microscopy revealed that the eosinophilic granules were smooth ball-shaped structures in the cytoplasm, ranging in size from 0.8 to 1.4µm. The overall findings indicate that the eosinophilic granules were best correlated with lysosomes. The eosinophilic granules in clear cell RCC are expanded lysosomes, and this may be used as a unique feature for confirming the pathologic diagnosis of clear cell RCC. The findings further support the view that clear cell RCC have phagocytic capacity due to their containing abundant lysosomes in the cytoplasm.

Outcomes of Patients With Advanced Renal Cell Carcinoma With Non-Clear Cell Histology Treated With Systemic Therapy

BackgroundPatients with nonclear cell renal cell carcinoma (RCC) and RCC with sarcomatoid differentiation have been under-represented in clinical trials. This study evaluates the outcomes and treatment patterns of patients with non-clear cell RCC and RCC with sarcomatoid features compared to those with clear cell RCC receiving systemic therapy. MethodsA single-center retrospective analysis of patients with advanced or metastatic RCC receiving systemic therapy was conducted. Patients were divided into groups based on histology: nonclear cell RCC, clear cell RCC, and RCC with and without sarcomatoid features. The primary endpoint was overall survival (OS) for each group calculated from the date of diagnosis of advanced or metastatic RCC to the date of last follow-up or death. Additionally, an exploratory analysis was conducted by nonclear cell type and type of first-line treatment. ResultsOverall, 251 patients were included, with most treated before 2018. First-line therapies included vascular endothelial growth factor monotherapy (68.5%), immunotherapy monotherapy (7.6%), immunotherapy combination therapy (16.7%), or other treatments (7.2%). Overall survival was shorter for patients with nonclear cell RCC compared to clear cell RCC (39.2 months vs. 81.1 months, hazard ratio (HR), 1.60, 95% Confidence Interval 1.0, 2.6, P = .04). Additionally, OS for patients with sarcomatoid differentiation was shorter compared to patients without sarcomatoid differentiation (43.4 vs. 75.0 months, HR 1.5, 95% CI 0.8, 2.6, P = .20). ConclusionWe demonstrate inferior outcomes among patients with advanced or metastatic nonclear cell RCC and RCC with sarcomatoid differentiation receiving systemic treatment. Further prospective studies are warranted testing immunotherapy combinations and novel treatments in patients with nonclear cell RCC.