Histological Subtypes Of Renal Cell Carcinoma Research Articles

Emerging innovative treatment strategies for advanced clear cell renal cell carcinoma.

Dramatic advances in biological discoveries, since the 1990s, have continued to reshape the treatment paradigm of metastatic renal cell carcinoma (RCC). Von Hippel Lindau (VHL) gene alterations are associated with pro-angiogenic activity and are central to the pathogenesis of clear cell RCC (ccRCC), the most predominant histologic subtype of RCC. Antiangiogenic strategies revolving around this VHL/HIF/VEGF axis have been shown to improve survival in metastatic ccRCC. The discovery of immune checkpoints and agents that target their inhibition introduced a new treatment paradigm for patients with RCC. While initially approved as monotherapy, studies investigating immune checkpoint inhibitor combinations have led to their approval as the new standard of care, providing durable responses and unprecedented improvements in clinical outcome. Despite these advances, the projected 14390 deaths in 2024 from RCC underscore the need to continue efforts in expanding and optimizing treatment options for patients with metastatic RCC. This article reviews key findings that have transformed the way we understand and treat metastatic RCC, in addition to highlighting novel treatment strategies that are currently under development.

Abstract A059: Racial and ethnic variation in obesity rates and body composition and their associations with renal cell carcinoma grade, stage, and histologic subtype

Abstract Background: Obesity is more prevalent in minoritized groups, including Hispanics, American Indian (AI), and non-Hispanic Black (NHB), and these groups have higher renal cell carcinoma (RCC) incidence and mortality rates than non-Hispanic White (NHW). However, the role of abdominal adiposity in RCC disparities are still unknown. To address this gap, we investigated body composition variation and associations with RCC pathological characteristics accounting for neighborhood characteristics. Methods: Social vulnerability index (SVI) scores were linked to the zip code of patient’s residence. Preoperative CT and MRI scans were obtained. SliceOmatic software was used to measure intermuscular, visceral, and subcutaneous adipose tissue and skeletal muscle areas and were normalized for height to obtain intermuscular, visceral, and subcutaneous adipose tissue index (IMATI, VATI, and SATI) and skeletal muscle index (SMI). Non-parametric tests were used to examine correlations, and logistic regression analyses were performed to obtain odds ratio (OR) and confidence interval (CI). Results: A total of 235 patients, including 70 (29.8%) Hispanic, 17 (7.2%) AI, and 20 (8.5%) NHB, were included. Obesity was more common in Hispanic (58.6%), AI (70.6%), and NHB (60.0%) than NHW (47.9%) patients. Compared to NHW patients, SATI was higher in Hispanic (P<0.001) and AI (P=0.002), and VATI was higher in Hispanic patients (P=0.04). Patients from minoritized racial and ethnic groups were more likely to come from neighborhoods with high SVI. SVI was significantly positively correlated with BMI (P=0.02) and SATI (P<0.001). Among SVI themes, socioeconomic, housing and transportation, and minority and language characteristics were significantly positively correlated with SATI (P<0.01). All body composition measurements were significantly positively correlate with BMI (P<0.001). Patients from minoritized racial and ethnic groups were also more likely to have hypertension and diabetes, and patients with both conditions had higher BMI (P=0.002), IMATI (P<0.001), VATI (P<0.001), and SATI (P=0.01) than patients without either condition. Obesity was associated with reduced odds of high grade RCC (OR 0.53, 95% CI 0.29-0.93). After including comorbidities in the model, association was no longer significant. In the same model, AI patients showed a trend for increased odds of high grade (OR 3.28, 95% CI 0.85-12.62, P=0.08) compared to NHW patients. AI patients also had significantly increased odds of having advanced stage RCC (OR 3.72, 95% CI 1.14-12.19). The highest quartile of IMATI significantly increased odds of advanced stage (OR 4.53, 95% CI 1.43-14.36) and clear cell subtype (OR 5.87, 95% CI 1.17-29.55) compared to the lowest quartile with significant P for trend (0.009 and 0.03 respectively). The third quartile of VATI was also significantly associated with clear cell subtype (OR 13.27, 95% CI 13.27). Conclusion: Obesity rates and body composition vary among racially and ethnically diverse RCC patients and are associated with RCC pathological characteristics. Citation Format: Ken Batai, Juan Adrover Claudio, Robert M. Blew, Benjamin R. Lee, Hina Arif Tiwari, Patrick Wightman, Qian Liu, Charles L. Roche, Evan W Davis, Rikki Cannioto, Eric C. Kauffman, Jennifer W. Bea. Racial and ethnic variation in obesity rates and body composition and their associations with renal cell carcinoma grade, stage, and histologic subtype [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A059.

ASSOCIATION OF SMOKING STATUS, TYPE OF CIGARETTES AND OBESITY AS RISK FACTORS AMONG RENAL CELL CARCINOMA HISTOLOGICAL SUBTYPES

Objective: This study aims to know the relationship between smoking and obesity as a risk factor among renal cell carcinoma histological subtypes. Material & Methods: This was a retrospective case-control study, with 67 patients with Renal Cell Carcinoma (RCC) at the Department of Urology, Hasan Sadikin Academic Medical Center Bandung from January 2012 to December 2021 as the case group, and 13 patients with benign tumors as the control group. The odds ratio and its significance were calculated. Results: In clear cell RCC, smokers (p-value=0.008), showed strong relationship to cigarette types (p-value=0.013), and obesity (p-value=0.042). In papillary RCC, smokers (p-value=0.035) showed a strong relationship to cigarette types (p-value=0.041). Cloves have a higher risk compared to filtered cigarettes (OR 2.25, 95% CI [0.54-9.25]). Conclusion: Clear cell RCC is most prevalent in smokers. Obesity is associated with clear cell RCC. Cloves pose the greatest risk of clear cell and papillary RCC. Keywords: Obesity, RCC, smoking, cigarette.

Renal cell carcinoma histologic subtypes exhibit distinct transcriptional profiles.

Molecular profiling of clear cell renal cell carcinoma (ccRCC) tumors of patients in a clinical trial has identified distinct transcriptomic signatures with predictive value, yet data in non-clear cell variants (nccRCC) are lacking. We examined the transcriptional profiles of RCC tumors representing key molecular pathways, from a multi-institutional, real-world patient cohort, including ccRCC and centrally reviewed nccRCC samples. ccRCC had increased angiogenesis signature scores compared with the heterogeneous group of nccRCC tumors, while cell cycle, fatty acid oxidation/AMPK signaling, and fatty acid synthesis/pentose phosphate signature scores were increased in one or more nccRCC subtypes. Among both ccRCC and nccRCC tumors, T effector scores statistically correlated with increased immune cell infiltration and were more commonly associated with immunotherapy-related markers (PD-L1+/TMBhi/MSIhi). In conclusion, this study provides evidence of differential gene transcriptional profiles among ccRCC versus nccRCC tumors, providing insights for optimizing personalized and histology-specific therapeutic strategies for patients with advanced RCC.

Implications of MTHFD2 expression in renal cell carcinoma aggressiveness.

Renal cell carcinoma (RCC) is the most common type of cancer in kidney and is often diagnosed in advanced stages. Until now, there is no reliable biomarker to assess tumor prognosis during histopathological diagnosis. The Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) overexpression has been suggested as prognostic indicator for RCC, however, its protein profile needs to be clarified. This study investigated the MTHFD2 expression in different RCC cohorts, associating it with tumor characteristics and prognostic factors. Gene expression comparisons between non-neoplastic (NN) and tumor samples, as well as patients' survival analysis, were assessed using KM-Plotter tool. MTHFD2 protein pattern was evaluated in 117 RCC by immunohistochemistry and associations with prognosis, clinical and pathological data were investigated. The tumors exhibited higher MTHFD2 transcript levels than NN, being even higher in the metastatic group. Opposite gene expression patterns were found among clear cell renal cell carcinoma (ccRCC) and pappilary renal cell carcinoma (pRCC) subtypes, showing higher and lower expressions compared to NN samples respectively. Overexpression was associated with shorter overall survival for ccRCC and pRCC subtypes, and shorter recurrence-free survival for pRCC. The immunolabeling profile varied according to tumor subtypes, with lower intensity and expression scores in ccRCC compared to pRCC and to chromophobe renal cell carcinoma (chRCC). MTHFD2 protein expression was associated with larger tumors and higher Fuhrman grades. Although prognostic value of protein immunostaining was not confirmed, patients with higher MTHFD2 tended to have lower survival rates in the pRCC group. The results highlight MTHFD2 different patterns according to RCC histological subtypes, revealing marked variations at both the genetic and protein levels. The mRNA indicated tumor prognosis, and greater expression in the tumor samples. Although MTHFD2 immunolabeling suggests tumor aggressiveness, it needs to be validated in other cohorts as potential prognostic factor.

Differential immunohistochemical expression of Galectin-1 and Galectin-3 in renal cell carcinoma

Background Renal cell carcinoma (RCC) is a heterogeneous cancer with many histological and molecular subtypes. Many new potential diagnostic, prognostic, and predictive biomarkers are still emerging. RCC treatment approaches are plentiful, including surgical resection, ablation, and active surveillance as well as immunotherapy. However, many cases are nonresponsive to such modalities and others experience recurrence or metastatic disease. Accordingly, the research work nowadays is concerned with looking for new targeted therapy biomarkers to treat RCC. Galectin-1 and Galectin-3 are the proposed biomarkers for this issue. Aim and methods This work aims to review the expression of Galectin-1 and Galectin-3 immune markers among the main histological subtypes of RCC and their correlation with clinicopathological parameters. To carry out this work, 60 cases of RCC were included in this study: 36 clear RCC, 16 papillary RCC I and II, and eight cases chromophobe RCC. Results Galectin-1 was highly expressed in 42 out of 60 cases, while Galectin-3 was highly expressed in only 13 cases. There was a statistically significant association between Galectin-1 and Galectin-3 expression and the histological subtype being expressed more in chromophobe subtype rather than others. There was a statistically significant inverse association between Galectin-1 expression and lymphovascular invasion as well as Galectin-3 expression and tumor necrosis and hemorrhage. There was no statistically significant association between Galectin-1 and 3 and the remaining clinicopathological parameters. Conclusion Galectin-1 and Galectin-3 could be used as potential diagnostic markers for chromophobe RCC as they are highly expressed in this subtype in comparison to others and can be used as targeted biomarkers for RCC therapy in the future. Galectin-3 has an anti-necrotic role and this could lead to chemotherapy resistance.

PSMA-Expression Is Highly Associated with Histological Subtypes of Renal Cell Carcinoma: Potential Implications for Theranostic Approaches.

In renal cell carcinoma (RCC), accurate imaging methods are required for treatment planning and response assessment to therapy. In addition, there is an urgent need for new therapeutic options, especially in metastatic RCC. One way to combine diagnostics and therapy in a so-called theranostic approach is the use of radioligands directed against surface antigens. For instance, radioligands against prostate-specific membrane antigen (PSMA) have already been successfully used for diagnosis and radionuclide therapy of metastatic prostate cancer. Recent studies have demonstrated that PSMA is expressed not only in prostate cancer but also in the neovasculature of several solid tumors, which has raised hopes to use PSMA-guided theranostic approaches in other tumor entities, too. However, data on PSMA expression in different histopathological subtypes of RCC are sparse. Because a better understanding of PSMA expression in RCC is critical to assess which patients would benefit most from theranostic approaches using PSMA-targeted ligands, we investigated the expression pattern of PSMA in different subtypes of RCC on protein level. Immunohistochemical staining for PSMA was performed on formalin-fixed, paraffin-embedded archival material of major different histological subtypes of RCC (clear cell RCC (ccRCC)), papillary RCC (pRCC) and chromophobe RCC (cpRCC). The extent and intensity of PSMA staining were scored semi-quantitatively and correlated with the histological RCC subtypes. Group comparisons were calculated with the Kruskal-Wallis test. In all cases, immunoreactivity was detected only in the tumor-associated vessels and not in tumor cells. Staining intensity was the strongest in ccRCC, followed by cpRCC and pRCC. ccRCC showed the most diffuse staining pattern, followed by cpRCC and pRCC. Our results provide a rationale for PSMA-targeted theranostic approaches in ccRCC and cpRCC.

Differential expression of HIF1A and its downstream target VEGFA in the main subtypes of renal cell carcinoma and their impact on patient survival.

Renal cell carcinoma (RCC) represents around 3% of all cancers, with the most frequent histological types being clear-cell RCC (ccRCC), followed by papillary (pRCC) and chromophobe (chRCC). Hypoxia-inducible factors (HIFs), which promote the expression of various target genes, including vascular endothelial growth factor (VEGF) and the high- affinity glucose transporter 1, have an important role in the pathogenesis of RCC. This study investigated the immunohistochemical expression of HIF-1α and VEGF-A, showing significantly higher HIF-1α nuclear expression in pRCC compared to ccRCC, while there was no significant difference in VEGF-A protein expression between the analyzed histological RCC subtypes. The quantitative reverse transcription polymerase chain reaction for HIF1A showed no statistical difference between histological types. Data from publicly available RNA sequencing databases were analyzed and showed that, compared to healthy kidney tissue, VEGFA was significantly up-regulated in ccRCC and significantly down-regulated in pRCC. The comparison between histological subtypes of RCC revealed that VEGFA was significantly up-regulated in ccRCC compared to both pRCC and chRCC. There was no statistically significant difference in survival time between HIF1A high- and low-expression groups of patients. As for VEGFA expression, pRCC patients with low expression had a significantly higher survival rate compared to patients with high VEGFA expression.

Renal cell carcinoma

SummaryKidney cancer accounts for 5% and 3% of all adult malignancies in men and women. Renal cell carcinoma (RCC) accounts for approximately 80% of all kidney cancer. This year’s American Society of Clinical Oncology (ASCO) Annual Meeting was held from 2–6 June 2023, in Chicago, USA. Combination therapies for advanced RCC continue to be of interest at ASCO 2023, with the presentation of updated results from some ongoing studies. There were several studies presented at ASCO looking at treatments for non clear renal cell carcinoma. Immunotherapy- based therapy regimes are now the gold standard for rare histological subtypes of RCC.

The Metastasis Pattern of Renal Cell Carcinoma Is Influenced by Histologic Subtype, Grade, and Sarcomatoid Differentiation.

Background and Objectives: Metastasis is a major cause of death in renal cell carcinoma (RCC) patients; therefore, a better understanding of the metastatic process and the ability to predict metastasis in advance is important for treating patients with RCC. This study aimed to investigate whether histological subtypes of RCC and other factors, such as nuclear grade and sarcomatoid differentiation, could predict the probability and location of metastases in patients with RCC. Materials and Methods: Cases of clear-cell, papillary, chromophobe, and sarcomatoid RCC were retrieved and analyzed from the Surveillance, Epidemiology, and End Results databases. Results: When comparing the metastatic patterns among the three histologic subtypes, patients with clear-cell RCC were significantly more likely to have brain and lung metastases. Moreover, patients with papillary RCC were significantly less likely to develop bone metastases and more likely to develop lymph node metastases. Patients with chromophobe RCC are significantly more likely to develop liver metastases. As the nuclear grade increased, there was also a significantly increased tendency for clear-cell RCC to metastasize to the lungs. Patients with sarcomatoid RCC had a higher rate of metastasis, with a significantly higher probability of metastasis to the bone and lungs, than those with all three histological subtypes did. Conclusions: Histological subtype, nuclear grade, and sarcomatoid differentiation were significant predictors of metastasis in patients with RCC.

Chromophobe: A rare histological variant of renal cell carcinoma

Background: Renal cell carcinoma (RCC) is an adenocarcima of the kidney. It is a highly heterogeneous disease with sixteen known subtypes out of which five predominate. The most common subtype is clear cell RCC which accounts for 75-85%. The chromophobe subtype of RCC is rarely seen. It is reported to constitute 4-5% of RCC subtype. This study was aimed at reporting the first case of chromophobe renal cell carcinoma in our community a rare histological subtype of RCC which was discovered incidentally. Our objective was to describe the clinical, histological and immunohistochemical evaluation of a case of chromophobe RCC.
 Case report: We present a 60-year-old man who was seen at the surgical outpatient department of our center with a request for general health check-up. He had basic laboratory and imaging investigations. These were essentially normal except for an incidental finding of a left renal mass on abdominopelvic sonogram. Computed tomography urography showed a suspected clinically localized malignant left renal mass. Histological and immunohistochemistry are consistent with a chromophobe RCC. His clinic follow-up remains unremarkable.
 Conclusion: We reported the clinical, histological and immunohistochemical evaluation of a rare case of chromophobe RCC. This was discovered incidentally following general health check. He had open radical nephrectomy and clinic follow-up 1 year after discharge has been uneventful.

Abstract B010: Germline susceptibility to renal cell carcinoma and implications for genetic screening

Abstract Background: Genetic susceptibility to renal cell carcinoma (RCC) remains poorly understood and limited to specific hereditary cancer syndromes. Whereas few studies have investigated rare germline variants in specific populations, the majority of them have not taken into account differences between histological subtypes of RCC. Objective: To identify common risk-genes for RCC within the Canadian population, investigate their association to clinical annotations and outcomes, and compare gene-burden among RCC patients from various countries. Methods: We conducted targeted DNA sequencing of 19 RCC-related and 27 cancer predisposition genes for 960 RCC patients (759 with clear cell and 201 with non-clear cell RCC) from Canada. We identified genes enriched in rare germline pathogenic variants (PVs) in RCC compared to a cancer-free control population (gnomAD, n=118148). Gene associations to RCC subtypes and clinical annotations were examined using Firth’s logistic regression models and Fisher’s exact tests, respectively. In addition, we compared prevalence of PVs in Canadian patients to those in previous studies from Japan (n=1632), the UK (n=1336) and the USA (n=254). Furthermore, we evaluated the performance of current criteria for RCC genetic screening for including patients with PVs in Canada, the US, and the UK. Results: We identified 39 germline PVs in 56 RCC patients from the Canadian cohort. Compared to cancer-free controls, PVs in MITF (OR: 212.3, 95% CI: 4.0-6.8, p= 1.44 × 10−9), CHEK2 (OR: 4.8, 95% CI: 1.0-2.1, p=3.94 × 10−5), and ATM (OR: 4.5, 95% CI: 0.7-2.2, p=0.016) genes were significantly enriched in patients with clear cell RCC, whereas PVs in FH (OR: 215.1, 95% CI: 4.2-6.4, p=6.14 × 10−9) were enriched in patients with non-clear cell RCC. We observed an association between PVs in DNA repair genes BRCA1, BRCA2 and ATM with the presence of metastasis in ccRCC (p=0.004) and RCC overall (p=0.003). Comparisons of gene-burden to other populations showed an enrichment for TP53 in RCC patients from Japan, while RCC patients from Canada showed an enrichment for CHEK2 and ATM. RCC patients from the US showed an enrichment for germline PVs in FH in comparison to Canadians. Notably, our analysis reveals that current criteria for referral to genetic screening for hereditary renal cancer fail to include the majority (73%) of patients harboring rare germline PVs in risk genes for RCC, both in Canada and globally. Conclusions: MITF, CHEK2, ATM, and FH were identified as risk-genes for RCC within the Canadian population, while germline mutations in BRCA1/2 and ATM are associated with risk of metastasis. Globally, clinical guidelines for genetic screening in RCC fail to identify up to 80% of patients with rare germline PVs. Citation Format: Kate I. Glennon, Mikiko Endo, Yoshiaki Usui, Yusuke Iwasaki, Rodney H. Breau, Anil Kapoor, Simon Tanguay, Yukihide Momozawa, Yasser Riazalhosseini. Germline susceptibility to renal cell carcinoma and implications for genetic screening [abstract]. In: Proceedings of the AACR Special Conference: Advances in Kidney Cancer Research; 2023 Jun 24-27; Austin, Texas. Philadelphia (PA): AACR; Cancer Res 2023;83(16 Suppl):Abstract nr B010.

Characterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles.

To characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry). Formalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients. Patients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK+ tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68+) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4+ T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8+ T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable. Our findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications.

EphrinB2: Expression of a novel potential target in renal cell carcinoma.

Renal cell carcinoma (RCC) is primarily managed by surgery with the use of systemic targeted therapy in a metastatic setting. Newer targeted therapeutic options are evolving; Eph-ephrin is a potential new pathway. The therapeutic potential of targeting the EphB4-EphrinB2 pathway has been demonstrated in many solid tumors; however, its expression in RCC has only been evaluated in a few studies with limited cases. We herein determine the immunohistochemical expression of EphrinB2 in RCC. A tissue microarray comprising 110 cases of different histological subtypes of RCC and 10 normal kidney tissues were stained with monoclonal anti-EphrinB2 antibody (Abcam, AB201512). The tumor and endothelial cells expressing the EphrinB2 were examined and its expression was correlated with sex, histological subtypes, and tumor nodes metastasis (TNM) stage. Twenty cases of urothelial carcinoma and two unsatisfactory conventional clear cell RCC cases were excluded, and EphrinB2 expression was interpreted in the remaining 88 tumors. EphrinB2 was expressed in 42 out of 88 tumors (47.7%) and was negative in the normal renal parenchyma. There was a statistically significant difference in the expression of EphrinB2 in males (55%) and females (32%). However, no such difference of expression was noted for the histological subtypes and the stages. Half (51%) of Stage 1 (n = 30) and Stage 2 (n = 11) tumors showed EphrinB2 positivity. EphrinB2 is expressed in approximately half of RCC cases. EphrinB2 expression in the early stage cancer might indicate its induction as an early event.

Distinguishing Renal Cell Carcinoma From Normal Kidney Tissue Using Mass Spectrometry Imaging Combined With Machine Learning.

Accurately distinguishing renal cell carcinoma (RCC) from normal kidney tissue is critical for identifying positive surgical margins (PSMs) during partial and radical nephrectomy, which remains the primary intervention for localized RCC. Techniques that detect PSM with higher accuracy and faster turnaround time than intraoperative frozen section (IFS) analysis can help decrease reoperation rates, relieve patient anxiety and costs, and potentially improve patient outcomes. Here, we extended our combined desorption electrospray ionization mass spectrometry imaging (DESI-MSI) and machine learning methodology to identify metabolite and lipid species from tissue surfaces that can distinguish normal tissues from clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC) tissues. From 24 normal and 40 renal cancer (23 ccRCC, 13 pRCC, and 4 chRCC) tissues, we developed a multinomial lasso classifier that selects 281 total analytes from over 27,000 detected molecular species that distinguishes all histological subtypes of RCC from normal kidney tissues with 84.5% accuracy. On the basis of independent test data reflecting distinct patient populations, the classifier achieves 85.4% and 91.2% accuracy on a Stanford test set (20 normal and 28 RCC) and a Baylor-UT Austin test set (16 normal and 41 RCC), respectively. The majority of the model's selected features show consistent trends across data sets affirming its stable performance, where the suppression of arachidonic acid metabolism is identified as a shared molecular feature of ccRCC and pRCC. Together, these results indicate that signatures derived from DESI-MSI combined with machine learning may be used to rapidly determine surgical margin status with accuracies that meet or exceed those reported for IFS.

MP41-15 DIFFERENCES IN SOMATIC AND GERMLINE VARIATIONS IN HISPANIC AND NON-HISPANIC PATIENTS WITH RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 Apr 2023MP41-15 DIFFERENCES IN SOMATIC AND GERMLINE VARIATIONS IN HISPANIC AND NON-HISPANIC PATIENTS WITH RENAL CELL CARCINOMA Peris Castaneda, Eric Lo, John Heard, Michael Nazmifar, Michael Kheshvadjian, and Michael Ahdoot Peris CastanedaPeris Castaneda More articles by this author , Eric LoEric Lo More articles by this author , John HeardJohn Heard More articles by this author , Michael NazmifarMichael Nazmifar More articles by this author , Michael KheshvadjianMichael Kheshvadjian More articles by this author , and Michael AhdootMichael Ahdoot More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003279.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Among patients with renal cell carcinoma (RCC), those of Hispanic ethnicity have worse disease burden. Hispanic patients (HP) are diagnosed at a younger age and have higher stage disease at diagnosis. Although some of the disparity is due to social factors, studies have shown differences in RCC histologic subtype between HP and non-Hispanic white patients. This suggests a potential molecular component conferring greater pre-treatment disease. HP have been underrepresented in molecular genomic studies of RCC and data on gene variation are lacking. Here, we aim to determine differences in germline and somatic alterations in HP and non-Hispanic patients (NHP) with RCC. METHODS: We queried a multi-institutional pan-cancer database of >5 million patients for patients aged ≥18 diagnosed with RCC. Demographic factors and disease-specific factors were compared between HP and NHP to assess for statistical significance (p<0.05). Frequency and type of germline and somatic alterations were compared. RESULTS: We identified 558 HP and 4829 NHP with RCC. No difference in gender distribution was observed. HP were younger at diagnosis (57.3 years vs 61.4 years in NHP) (p<0.001) and more likely to be diagnosed at or before age 46 (20% vs 11% in NHP) (p<0.001). Fifty-seven percent of HP reported being never smokers compared to 40% of NHP (p<0.001). A higher proportion of HP presented with T4 or T3 disease (75%, compared to 43% of NHP). Overall, somatic variant information was available for 166 HP and 667 NHP; germline variant information was available for 38 HP and 667 NHP. The most common somatic and germline variants in HP and NHW are shown in Figure 1. Overall, somatic alterations appeared commensurate with the general RCC population. HP showed higher rates of germline alterations in CHEK2, MSH6, FH, and FLCN compared to NHP. CONCLUSIONS: Differences in germline alterations are observed between HP and NHP with RCC. Further genomic studies that include HP are needed to better identify targetable genetic alterations and improve treatment decisions. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e561 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Peris Castaneda More articles by this author Eric Lo More articles by this author John Heard More articles by this author Michael Nazmifar More articles by this author Michael Kheshvadjian More articles by this author Michael Ahdoot More articles by this author Expand All Advertisement PDF downloadLoading ...

Epigenomic charting and functional annotation of risk loci in renal cell carcinoma

While the mutational and transcriptional landscapes of renal cell carcinoma (RCC) are well-known, the epigenome is poorly understood. We characterize the epigenome of clear cell (ccRCC), papillary (pRCC), and chromophobe RCC (chRCC) by using ChIP-seq, ATAC-Seq, RNA-seq, and SNP arrays. We integrate 153 individual data sets from 42 patients and nominate 50 histology-specific master transcription factors (MTF) to define RCC histologic subtypes, including EPAS1 and ETS-1 in ccRCC, HNF1B in pRCC, and FOXI1 in chRCC. We confirm histology-specific MTFs via immunohistochemistry including a ccRCC-specific TF, BHLHE41. FOXI1 overexpression with knock-down of EPAS1 in the 786-O ccRCC cell line induces transcriptional upregulation of chRCC-specific genes, TFCP2L1, ATP6V0D2, KIT, and INSRR, implicating FOXI1 as a MTF for chRCC. Integrating RCC GWAS risk SNPs with H3K27ac ChIP-seq and ATAC-seq data reveals that risk-variants are significantly enriched in allelically-imbalanced peaks. This epigenomic atlas in primary human samples provides a resource for future investigation.

Association of Radiological Features with Histological Features in Patients with Renal Cell Carcinoma: A Cross-sectional Study

Introduction: Renal Cell Carcinoma (RCC) is a group of neoplastic lesions with unique cytogenetic characteristics and histopathological features. The majority of studies till date on RCC have been focusing on tissue histology to plan neoadjuvant treatment in clinical settings. An accurate forecast of the histopathological subtype has clinical implications in management and response to newer treatment strategies. It is pertinent to preoperatively distinguish a solid renal masses histologically but, there are currently no well-established imaging criteria to classify these tumors on the basis of radiographic evaluation. Aim: To evaluate the differences in imaging characteristics of different histological subtypes of RCC by Power Doppler Ultrasound and Multi-Detector Computed Tomography (MDCT) scan. Materials and Methods: This cross-sectional study was conducted in the Department of Urology, Gauhati Medical College and Hospital, Guwahati, Assam, from March 2016 to December 2017. The study population consisted of 61 patients of RCC who were evaluated with MDCT and Doppler ultrasound prior to surgery and findings were correlated with histopathological forms of tumour. The Pearson Chi-square test and ANOVA test was used to statistically analyse the data. Results: Histopathology revealed clear cell Renal Cell Carcinoma (ccRCC), chromophobe Renal Cell Carcinoma (chRCC) and papillary Renal Cell Carcinoma (pRCC) in 52, 4 and 5 patients, respectively. Heterogenous enhancement was found in 51 cases and among these 90.4% were ccRCC. Absolute attenuation values in Corticomedullary Phase (CMP) and Nephrographic Phase (NP) for clear cell and chromophobe subtype were higher than papillary subtype, i.e., 88.04±30.40 Hounsfield Unit (HU) and 72.41±20.17 HU for clear cell, 60.75±22.54 HU and 88±16.06 HU for chromophobe; 22.40±12.52 HU and 58.00±4.41 HU for papillary subtype, respectively. Papillary RCC (pRCC) showed a unique enhancement pattern, with a low peak enhancement (average peak of 55.40 HU) and greatest enhancement during the NP. In this study population ccRCC, ChRCC RCC and pRCC had mean Resistive Index (RI) of 0.63±0.06, 0.58±0.0 and 0.67±0.11, respectively. Conclusion: Power doppler flow imaging is not useful in discriminating subtypes of RCC while multiphasic Computed Tomography (CT) imaging may be useful, particularly the phasic enhancement pattern to distinguish common RCC subtypes which may facilitate treatment planning and choosing appropriate tyrosine kinase inhibitors.

Eosinophilic solid and cystic renal cell carcinoma: a single Indian tertiary center experience of three cases of a newly described entity

BackgroundAmong adult malignant tumors, renal cell carcinoma accounts for 2–3% and has the worst prognosis among common urologic tumors. Recently, an eosinophilic, solid and cystic (ESC) renal cell carcinoma (RCC) histological subtype has been described and proposed as an entity separate than the 16 subtypes described in the 2016 WHO classification. The aim of the present study is to share our experience of three such cases of this newly described entity.MethodsWe retrospectively reviewed our cases of renal cell carcinoma and describe the presentation, diagnosis and management with follow-up details of ESC RCC.ResultsOur three patients presented at an advanced stage with flank pain or mass, and one patient had metastasis. All patients underwent radical nephrectomy, diagnosis proved by histopathological examination with immunohistochemistry (IHC), with abundant eosinophilic cytoplasm in all three cases. On IHC, CK 20 was positive in two cases and one patient with CK 20, CK 7 negative and PAX 8 positive.ConclusionsESC RCC is a newly described entity, with increasing incidence probably due to better diagnosis. Previously, 66 such cases are described, with female predominance, lower stage and indolent behavior. Only four cases with metastasis are described.

Histological features suggestive of survival in patients with renal cell carcinoma and tumor thrombus: A single-center experience.

PurposeTo evaluate the impact of histological subtype on the survival of patients with renal cell carcinoma (RCC) and tumor thrombus (TT).Patients and methodsWe retrospectively analyzed 350 patients with RCC and TT admitted to Chinese People’s Liberation Army General Hospital between January 2006 and June 2021. The patients underwent radical nephrectomy and thrombectomy using robot-assisted laparoscopic, laparoscopic, or open surgery. The clinical and pathological parameters of the patients were taken from their medical records. Survival was calculated with the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of variables on overall survival (OS) and progression-free survival (PFS).ResultsTT levels 0–IV were observed in 132 (37.71%), 43 (12.29%), 134 (38.29%), 20 (5.71) and 21 (6.00%) patients, respectively. Papillary (pRCC), clear cell, and other histological subtypes of RCC were detected in 28 (8.00%), 286 (81.71%), and 36 (10.29%) patients, respectively. Compared to the clear cell cohort, collecting systemic invasion (46.43 vs. 25.17%; p = 0.030) and lymph node metastasis (39.29 vs. 11.54%; p < 0.01) were more common in the pRCC cohort. Kaplan–Meier analyses showed that patients with pRCC and other subtypes had significantly worse OS and PFS compared to patients with the clear cell subtype (p < 0.05). Multivariate analyses revealed that histology was independently associated with reduced OS and PFS, including among patients without lymph node and distant metastasis (N0M0).ConclusionPapillary or other subtypes have a considerably shorter OS and PFS compared to clear cell subtype in RCC patients with TT. Strict follow-up and surveillance should be performed for papillary or other subtypes RCC with TT.