Staging Of Renal Cell Carcinoma Research Articles

SCGN recruits macrophages by regulating chemokine secretion in clear cell renal cell carcinoma.

Immunotherapy is considered to be one of the most promising curative modalities for cancer, and the effectiveness of immunotherapy depends on the abundance of immune cells in the tumor microenvironment (TME). Immunotherapy tends to be more effective in "hot tumors" characterized by a high abundant immune cells. Our previous studies found that secretagogin (SCGN) showed intranuclear aggregation in the early stages of clear cell renal cell carcinoma (ccRCC) development. However, with tumor progression and distant metastasis of the ccRCC, the expression of SCGN is gradually absent. In this study, we found that SCGN did not affect the malignant phenotype of cancer cells, but could regulate cytokine/chemokine secretion and immune cell migration by performing gene function assays and RNA-seq analyses after overexpressing SCGN in cell lines of ccRCC. Bioinformatics analysis, Transwell and co-culture experiments confirmed that ccRCC cells overexpressing SCGN could recruit M1-type macrophages. Mechanistically, SCGN initiates downstream cytokine/chemokine expression and secretion through the NF-κB signal pathway. This study provides a comprehensive understanding of the function of SCGN in ccRCC. Continuous forced expression of SCGN at different stages may be a potential approach for the treatment of ccRCC.

Prevalence and Significance of AGR2 Expression in Human Cancer.

Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing. To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%-100%), urothelial carcinoma (74.6%-100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%-99.6%), and pancreaticobiliary cancers (65.2%-98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%-77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (p < 0.0001), Fuhrman (p < 0.0001), and Thoenes (p < 0.0001) grades as well as advanced pT stage (p = 0.0035) in clear cell renal cell carcinoma (ccRCC). Low AGR2 expression was associated with high BRE grade in breast cancer (p = 0.0049), nodal metastasis (p = 0.0275) and RAS mutation (p = 0.0136) in colorectal cancer, nodal metastasis (p = 0.0482) in endometrioid endometrial carcinoma, high grade in noninvasive urothelial carcinoma (p = 0.0003), and invasive tumor growth in urothelial carcinoma (p < 0.0001). It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.

Application of artificial intelligence model in pathological staging and prognosis of clear cell renal cell carcinoma

This study aims to develop a deep learning (DL) model based on whole-slide images (WSIs) to predict the pathological stage of clear cell renal cell carcinoma (ccRCC). The histopathological images of 513 ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA) database and randomly divided into training set and validation set according to the ratio of 8∶2. The CLAM algorithm was used to establish the DL model, and the stability of the model was evaluated in the external validation set. DL features were extracted from the model to construct a prognostic risk model, which was validated in an external dataset. The results showed that the DL model showed excellent prediction ability with an area under the curve (AUC) of 0.875 and an average accuracy score of 0.809, indicating that the model could reliably distinguish ccRCC patients at different stages from histopathological images. In addition, the prognostic risk model constructed by DL characteristics showed that the overall survival rate of patients in the high-risk group was significantly lower than that in the low-risk group (P = 0.003), and AUC values for predicting 1-, 3- and 5-year overall survival rates were 0.68, 0.69 and 0.69, respectively, indicating that the prediction model had high sensitivity and specificity. The results of the validation set are consistent with the above results. Therefore, DL model can accurately predict the pathological stage and prognosis of ccRCC patients, and provide certain reference value for clinical diagnosis.

6477 Surprise Finding For A Thyroid Nodule: Metastatic Renal Cell Carcinoma

Abstract Disclosure: A. Xu: None. E. Hsu: None. Introduction: A patient with an incidental and asymptomatic thyroid nodule underwent fine needle aspiration biopsy (FNA) after the nodule increased in size. Without a definite pathology after three FNA attempts, thyroidectomy was performed, where pathology found metastatic renal cell carcinoma (RCC). Clinical Case: A 64 year old woman had a past medical history of obesity, type 2 diabetes, RCC (stage I: pT1bN0M0) treated with right radical nephrectomy five years prior and thought to be in remission, remote smoking history smoking, and coronary artery disease with coronary artery bypass graft (CABG) two months prior, on anticoagulation. The patient reported a distant history of right thyroid lobectomy over a decade prior for unclear reasons, but she was adamant that the pathology was benign. Two years prior to presentation, CT chest done for RCC surveillance had detected a left thyroid nodule. Ultrasound at the time revealed a 3.6 x 1.9 x 2.3 cm solid, isoechoic nodule in the upper left lobe, which was not taller than wide, and had smooth margins and no echogenic foci. A repeat ultrasound at the time of presentation showed interval growth of the nodule, now measuring 4.3 x 2.1 x 2.9 cm. FNA was unsatisfactory, yielding predominantly blood. Patient felt well and had no compressive neck symptoms. We opted to wait two months and repeat FNA, which resulted as atypia of undetermined significance - Bethesda category III (AUS). We recommended completion thyroidectomy, but patient preferred to avoid surgery. We decided to wait two months and repeat FNA with molecular testing. This third FNA resulted AUS again; however, due to non-medical reasons, molecular testing was not performed. Another ultrasound showed slight growth of the nodule, 5.1 x 2.9 x 2.0 cm, which appeared hypoechoic now, but was still not taller than wide, with smooth margins and no echogenic foci. Completion thyroidectomy was performed, with pathology showing metastatic clear cell renal cell carcinoma. Immunostains were positive for carbonic anhydrase and renal cell carcinoma marker and negative for TTF-1. Whole-body PET-CT showed no hypermetabolic foci, and a repeat PET-CT one year later still showed no evidence of metastatic disease. Other than a hospitalization for COVID-19, patient is doing well and asymptomatic now over a year after her thyroidectomy. Oncology will continue routine surveillance imaging for her metastatic renal cell carcinoma thought to be in remission. Clinical Lessons: This case of metastatic renal cell carcinoma to the thyroid adds to the small body of literature showing the thyroid as a possible site of RCC metastasis. The long time interval between initial RCC presentation and metastasis to the thyroid makes this diagnosis more difficult; however, clinicians should be aware of the possibility, making thyroidectomy a stronger option in cases where FNA cytology is indeterminate. Presentation: 6/2/2024

6477 Surprise Finding for a Thyroid Nodule: Metastatic Renal Cell Carcinoma

Abstract Disclosure: A. Xu: None. E. Hsu: None. Introduction: A patient with an incidental and asymptomatic thyroid nodule underwent fine needle aspiration biopsy (FNA) after the nodule increased in size. Without a definite pathology after three FNA attempts, thyroidectomy was performed, where pathology found metastatic renal cell carcinoma (RCC). Clinical Case: A 64 year old woman had a past medical history of obesity, type 2 diabetes, RCC (stage I: pT1bN0M0) treated with right radical nephrectomy five years prior and thought to be in remission, remote smoking history smoking, and coronary artery disease with coronary artery bypass graft (CABG) two months prior, on anticoagulation. The patient reported a distant history of right thyroid lobectomy over a decade prior for unclear reasons, but she was adamant that the pathology was benign. Two years prior to presentation, CT chest done for RCC surveillance had detected a left thyroid nodule. Ultrasound at the time revealed a 3.6 x 1.9 x 2.3 cm solid, isoechoic nodule in the upper left lobe, which was not taller than wide, and had smooth margins and no echogenic foci. A repeat ultrasound at the time of presentation showed interval growth of the nodule, now measuring 4.3 x 2.1 x 2.9 cm. FNA was unsatisfactory, yielding predominantly blood. Patient felt well and had no compressive neck symptoms. We opted to wait two months and repeat FNA, which resulted as atypia of undetermined significance - Bethesda category III (AUS). We recommended completion thyroidectomy, but patient preferred to avoid surgery. We decided to wait two months and repeat FNA with molecular testing. This third FNA resulted AUS again; however, due to non-medical reasons, molecular testing was not performed. Another ultrasound showed slight growth of the nodule, 5.1 x 2.9 x 2.0 cm, which appeared hypoechoic now, but was still not taller than wide, with smooth margins and no echogenic foci. Completion thyroidectomy was performed, with pathology showing metastatic clear cell renal cell carcinoma. Immunostains were positive for carbonic anhydrase and renal cell carcinoma marker and negative for TTF-1. Whole-body PET-CT showed no hypermetabolic foci, and a repeat PET-CT one year later still showed no evidence of metastatic disease. Other than a hospitalization for COVID-19, patient is doing well and asymptomatic now over a year after her thyroidectomy. Oncology will continue routine surveillance imaging for her metastatic renal cell carcinoma thought to be in remission. Clinical Lessons: This case of metastatic renal cell carcinoma to the thyroid adds to the small body of literature showing the thyroid as a possible site of RCC metastasis. The long time interval between initial RCC presentation and metastasis to the thyroid makes this diagnosis more difficult; however, clinicians should be aware of the possibility, making thyroidectomy a stronger option in cases where FNA cytology is indeterminate. Presentation: 6/2/2024

Curcumin Inhibits Vasculogenic Mimicry via Regulating ETS-1 in Renal Cell Carcinoma.

Metastatic renal cell carcinoma (RCC) poses a huge challenge once it has become resistant to targeted therapy. Vasculogenic mimicry (VM) is a novel blood supply system formed by tumor cells that can circumvent molecular targeted therapies. As one of the herbal remedies, curcumin has been demonstrated to play antineoplastic effects in many different types of human cancers; however, its function and mechanism of targeting VM in RCC remains unknown. Here, in the work, we explored the role of curcumin and its molecular mechanism in the regulation of VM formation in RCC. RNA-sequencing analysis, immunoblotting, and immunohistochemistry were used to detect E Twenty Six-1(ETS-1), vascular endothelial Cadherin (VE-Cadherin), and matrix metallopeptidase 9 (MMP9) expressions in RCC cells and tissues. RNA sequencing was used to screen the differential expressed genes. Plasmid transfections were used to transiently knock down or overexpress ETS-1. VM formation was determined by tube formation assay and animal experiments. CD31-PAS double staining was used to label the VM channels in patients and xenograft samples. Our results demonstrated that VM was positively correlated with RCC grades and stages using clinical patient samples. Curcumin inhibited VM formation in dose and time-dependent manner in vitro. Using RNA-sequencing analysis, we discovered ETS-1 as a potential transcriptional factor regulating VM formation. Knocking down or overexpression of ETS-1 decreased or increased the VM formation, respectively and regulated the expression of VE-Cadherin and MMP9. Curcumin could inhibit VM formation by suppressing ETS-1, VE-Cadherin, and MMP9 expression both in vitro and in vivo. Our finding might indicate that curcumin could inhibit VM by regulating ETS-1, VE-Cadherin, and MMP9 expression in RCC cell lines. Curcumin could be considered as a potential anti-cancer compound by inhibiting VM in RCC progression.

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&amp;lt;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&amp;lt;0.001). Among SVI themes, socioeconomic, housing and transportation, and minority and language characteristics were significantly positively correlated with SATI (P&amp;lt;0.01). All body composition measurements were significantly positively correlate with BMI (P&amp;lt;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&amp;lt;0.001), VATI (P&amp;lt;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.

Feasibility and Reproducibility of T2 Mapping Compared with Diffusion-Weighted Imaging in Solid Renal Masses.

Accurate prediction of renal mass subtypes, along with the WHO/ISUP grade and pathological T (pT) stage of clear cell renal cell carcinoma (ccRCC), is crucial for optimal decision making. Our study aimed to investigate the feasibility and reproducibility of motion-robust radial T2 mapping in differentiating lipid-poor angiomyolipoma (MFAML) from RCC and characterizing the WHO/ISUP grade and pT stage of ccRCC. Finally, 92 patients undergoing renal radial T2 mapping and ZOOMit DWI were recruited. The T2 values and apparent diffusion coefficient (ADC) were analyzed. Correlation coefficients were calculated between ADC and T2 values. Notably, ccRCC exhibited higher T2 and ADC values than MFAML (p < 0.05). T2 values were lower in the higher WHO/ISUP grade and pT stage of ccRCC (all p < 0.05). ADC showed no significant difference for pT stage (p = 0.056). T2 values revealed a higher area under the curve (AUC) in evaluating the WHO/ISUP grade compared to ADC (0.936 vs. 0.817, p = 0.027). T2 values moderately positively correlated with ADC (r = 0.675, p < 0.001). In conclusion, quantitative motion-robust radial T2 mapping is feasible for characterizing solid renal masses and could provide additional value for multiparametric imaging in predicting WHO/ISUP grade and pT stage of ccRCC.

Development and Validation of a Nomogram for Predicting Postoperative Recurrence-Free Survival in Patients With Nonmetastatic Pathological T3a Stage Renal Cell Carcinoma

BackgroundTo establish a nomogram predicting postoperative recurrence-free survival (RFS) in patients with nonmetastatic renal cell carcinoma (RCC) of pathological T3a (pT3a) stage undergoing nephrectomy. Materials and MethodsA retrospective review included 668 patients with pT3a RCC between 2008 and 2019, randomly divided into training and validation groups (7:3 ratio). Cox regression analysis established the RFS-predicting nomogram in the training group. Nomogram performance was assessed using Harrell's concordance index (C-index), time-dependent receiver operating characteristic curve, decision curve analysis, and Kaplan-Meier survival analysis. ResultsOf the 668 patients with pT3a RCC, 167 patients experienced local recurrence or distant metastasis. Using multivariable Cox regression analysis, tumor size, ISUP grade, necrosis, capsular invasion, pT3a invasion pattern were identified as the significant predictors for RFS to establish the nomogram. The C-index of the nomogram was 0.753 (95% CI, 0.710-0.796) and 0.762 (95% CI, 0.701-0.822) for the training and validating group, respectively. The areas under the 1-year, 3-year and 5-year RFS receiver operating characteristic curves were 0.814, 0.769 and 0.768, respectively. Decision curve analysis showed the optimal application of the model in clinical decision-making. Patients with low risk T3a RCC have better RFS than those with high risk T3a RCC. ConclusionTumor size, ISUP grade, necrosis, capsular invasion and T3a invasion patterns were independent risk factors for worse RFS in patients with nonmetastatic pT3a RCC. The current nomogram could effectively predict the RFS of patients with nonmetastatic pT3a RCC.

12 Concordance Analysis of Tissue and Circulating Tumor DNA (ctDNA) in Renal Cell Carcinoma (RCC): Insights from a Multimodal Real-World Database

Abstract Background Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) has emerged as a powerful complement to tissue NGS, offering a noninvasive and serially conductible test. Its application holds promise in enhancing the assessment of spatial and temporal molecular tumor heterogeneity, thus providing valuable insights into cancer progression and treatment response. In this study, we explore the mutational landscape of renal cell carcinoma (RCC) patients through comprehensive profiling of mutations in ctDNA and matched tissue samples, aiming to elucidate the concordance and clinical significance of molecular alterations detected in both circulating and tissue-derived DNA. Methods From the Tempus multimodal database, we retrospectively analyzed de-identified NGS data from patients with RCC that had dual tissue (Tempus xT, 648 genes) and ctDNA testing (Tempus xF, 105 genes). Patients with matched samples (collected +/- 90 days of one another) were included. We evaluated socio-demographic and clinical characteristics and select pathogenic somatic short variants (PSSV) and copy number variants [(amplifications and deletions, two copy number losses (CNL)]. Concordance analyses were restricted to the 105 genes tested on the ctDNA panel and further restricted to short variants, with the exception of amplifications and CNL detected by both xF and xT. Analysis was further stratified by metastatic status (n=260, metastatic, n=120 non-metastatic) prior to collection of both xT and xF. Results Among all patients (n=393), the median age was 61 years, and 71% were male. The patient cohort comprised a diverse population based on race, with 75% white, 12% African American, 4.8% Asian and 8% others. The median time from tissue to blood collection was 21 days (IQR, 7, 39). 67% (n=265) and 68% (n=266) had metastatic disease at the time of tissue and blood collection, respectively. The most common tissue sites were kidney (49%, n=189), bone (11%, n=43), lung (9%, n=34), lymph node (8%, n=29), liver (6%, n=23), and brain/CNS (4%, n=17). Genes harboring the most common PSSV in tissue included VHL (59% n=232), PBRM1 (31%, n=123), SETD2 (23%, n=91), TP53 (14%, n=54), BAP1 (12%, n=46) and TERT (11%, n=45). Genes with common PSSV in ctDNA included TP53 (23%, n=91), VHL (18%, n=69), BAP1 (6%, n=23), PBRM1 (5%, n=21), PTEN (4%, n=15), KRAS (4%, n=14) and NF2 (4%, n=14). The combination of tissue and ctDNA testing increased the detection of mutations (Table 1). There was higher concordance between somatic alterations in select genes among patients with metastases vs. non-metastases, including BAP1 (55.9% vs. 9.1%), TP53 (36.8% vs. 9.1%), VHL (32.3% vs. 12.5%), ARID1A (25% vs. 16.7%), and ATM (25% vs. 0%). Table 1: Detection of genetic mutations in tissue and ctDNA testing Conclusions The analysis conducted in this study highlights the complementary nature of ctDNA profiling alongside tissue-based NGS in RCC, demonstrating an increased detection of mutations. Particularly, we observed a higher concordance between ctDNA and tissue profiling in individuals with metastatic disease, suggesting the potential utility of ctDNA analysis in advanced stages of RCC. Further research is warranted to elucidate how longitudinal ctDNA analysis can delineate biomarkers of response and resistance at both the mutation and ctDNA fraction levels. Understanding these dynamics could offer valuable insights into disease progression and guide personalized treatment strategies for RCC patients. DOD CDMRP Funding: no

Interaction between microglial cells and CD1C+ B dendritic cells leads to CD8+ T cells depletion during the early stages of renal clear cell carcinoma.

Renal clear cell carcinoma (RCC) is a type of malignant tumor, which, in addition to surgical resection, radiotherapy, and chemotherapy, has been widely treated through immunotherapy recently. However, the influence of the tumor microenvironment and the infiltrating immune cells within it on immunotherapy remains unclear. It is imperative to study the interactions between various immune cells of RCC. The scRNA-seq dataset from GEO's database was used to analyze the immune cells present in tumor tissue and peripheral blood samples. Through quality control, clustering, and identification, the types and proportions of infiltrating immune cells were determined. The cellular differences were determined, and gene expression levels of the differentially present cells were investigated. A protein-protein interaction network analysis was performed using string. KEGG and GO analyses were performed to investigate abnormal activities. The microglia marker CD68 and CD1C+ B dendritic cells marker CD11C were detected using multiplex immunofluorescence staining. Many depleted CD8+ T cells (exhausted CD8+ T cells) appeared in tumor tissues as well as microglia. CD1C+ B dendritic cells did not infiltrate tumor tissues. HSPA1A was correlated with DNAJB1 in microglia. Compared with Paracancer tissues, microglia increased while CD1C+ B dendritic cells decreased in pathological stages I and I-II in cancerous tissues. An altered tumor microenvironment caused by increases in microglia in RCC in the early stage resulted in an inability of CD1C+ B dendritic cells to infiltrate, resulting in CD8+ T cells being unable to receive the antigens presented by them, and in turn being depleted in large quantities.

Retroperitoneal laparoscopic radical nephrectomy in the treatment of renal cancer: a 5-year single-center experience in resource-scare setting

Based on a retrospective hospital-based analysis, this study examines the results of retroperitoneal laparoscopic radical nephrectomy for patients with T1-T2 renal cell carcinoma (RCC) from January 2019 to December 2023. Of the 73 patients, 4.1% had TNM stage II tumors and 95.8% had TNM stage I tumors (53.4% T1a and 42.4% T1b). In terms of frequency, clear cell RCC accounted for 84.9%, with papillary RCC coming in at 9.6% and chromophobe RCC at 4.1%. Following surgery, four patients experienced fevers, one needed a blood transfusion, two had infections, and one had emergency surgery. Lumbar masses and hematuria were absent in all patients. Subsequent metastatic lesions and abnormalities of the renal fossa were not observed on follow-up ultrasounds. 4.1% of the deaths after 25.9 months were due to the disease, and 1.4% were caused by accidents. At one, two, three, and four years, the cumulative survival rates were 100%, 97.2%, and 92.8%, respectively. 48.1 months was the mean postoperative survival period. For RCC stages T1-2, retroperitoneal laparoscopic radical nephrectomy offers significant benefits and comparable results to open surgery.

Galectin-3: action and clinical utility in chronic kidney disease.

Chronic kidney disease is a significant cause of morbidity and mortality worldwide. In recent years, Galectin-3 has been put forward as a potential biomarker of chronic kidney disease progression. This review aims to assess the clinical utility of Galectin-3 in various pathological processes leading up to chronic kidney disease such as diabetes and lupus nephritis. We conducted a systematic search on PubMed from inception to September 2023, using the search term ("Galectin-3" OR "gal-3") AND ("renal" OR "kidney"). Galectin-3 has been shown to be both pro-fibrotic and protective against renal fibrosis through various mechanisms such as apoptotic body clearance and modulation of the Wnt pathway. Studies have found associations between raised Galectin-3, incidence and progression of chronic kidney disease. In lupus nephritis, Galectin-3 may serve as a biomarker for lupus nephritis activity. Although Galectin-3 inhibits cystogenesis, there is no correlation between total kidney volume and Galectin-3 in polycystic kidney disease. The role of Galectin-3 in staging and prognostication of renal cell carcinoma is yet to be determined. Galectin-3 has potential in predicting chronic kidney disease progression, in combination with other biomarkers. However, more trials are required given that present studies demonstrate conflicting results on the relationship between Galectin-3 and clinical outcomes in chronic kidney disease patients of varying aetiologies.

Cytotoxic T lymphocyte associated antigen-4 (CTLA4) expression with renal cell carcinoma subtype and staging

In Indonesia, approximately 45% of renal cell carcinoma (RCC) patients are at an advanced stage that requires checkpoint inhibition combination immunotherapy. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is associated with poor prognosis of RCC and it is the first checkpoint developed in cancer immunotherapy. This study aimed to investigate CTLA-4 expression among RCC subtypes and staging. Formalin fixed paraffin embedded (FFPE) tissue of RCC patients from 2018-2020 were obtained from the Department of Anatomical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr. Sardjito General Hospital, Yogyakarta. Expression of CTLA-4 among RCC subtypes and stage was measured using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and compared. Among the 40 patients involved in this study, the CTLA-4 expression was higher in papillary RCC/pRCC (95.88 + 31.58) compared to clear cell RCC/ccRCC (90.94 + 43.05). However, no significantly different in CTL-4 expression based on histologic subtypes and tumor stage (p&gt;0.05). In conclusion, neither the histologic subtype nor the tumor stage of RCC can be predicted by CTLA-4 expression.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + . Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55months [32.8-107.2] vs. 20months [9.0-45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1-4] vs. 1[1-1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70-0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97-1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01-1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06-1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07-1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07-1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04-1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01-1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM + . Furthermore, number (OR:1.08; 95% CI 1.04-1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09-1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM + . Survival analysis showed a median second PFS of 10.9years (95% CI 3.3-not reached) for LC and a 3.8years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5years (95% CI 4.4-not reached) for LC and 6years (95% CI 4.3-11.6) for RCCM + . Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression.

Update on Renal Cell Carcinoma Diagnosis with Novel Imaging Approaches.

This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for distinguishing low-attenuation, true enhancing solid masses from hyperdense cysts. By determining whether or not a renal mass is present, DECT could avoid the need for additional imaging studies, thereby reducing healthcare costs. DECT can also provide virtual unenhanced images, helping to reduce radiation exposure. The review then provides an update focusing on the advantages of multiparametric magnetic resonance (MR) imaging performance in the histological subtyping of RCC and in the differentiation of benign from malignant renal masses. A proposed standardized stepwise reading of images helps to identify clear cell RCC and papillary RCC with a high accuracy. Contrast-enhanced ultrasound may represent a promising diagnostic tool for the characterization of solid and cystic renal masses. Several combined pharmaceutical imaging strategies using both sestamibi and PSMA offer new opportunities in the diagnosis and staging of RCC, but their role in risk stratification needs to be evaluated. Although radiomics and tumor texture analysis are hampered by poor reproducibility and need standardization, they show promise in identifying new biomarkers for predicting tumor histology, clinical outcomes, overall survival, and the response to therapy. They have a wide range of potential applications but are still in the research phase. Artificial intelligence (AI) has shown encouraging results in tumor classification, grade, and prognosis. It is expected to play an important role in assessing the treatment response and advancing personalized medicine. The review then focuses on recently updated algorithms and guidelines. The Bosniak classification version 2019 incorporates MRI, precisely defines previously vague imaging terms, and allows a greater proportion of masses to be placed in lower-risk classes. Recent studies have reported an improved specificity of the higher-risk categories and better inter-reader agreement. The clear cell likelihood score, which adds standardization to the characterization of solid renal masses on MRI, has been validated in recent studies with high interobserver agreement. Finally, the review discusses the key imaging implications of the 2017 AUA guidelines for renal masses and localized renal cancer.

Renal cell carcinoma: an overview of the epidemiology, presentation, histopathological characteristics, and surgical treatment variation between old and new era – a cross-sectional study

Introduction: The landscape of renal cell carcinoma (RCC) diagnosis, staging, and treatment has evolved over the last decades. Our study to report our experience in this evolution over a 30-years’ time. Methodology: A database of patients who underwent nephrectomy for RCC was collected and compared between new era (2017–2021) and old era (1992–2001). Results: One hundred thirty-six patients collected in new era compared to 132 in old era, results showed that more patients diagnosed at earlier stage and grade with smaller size of tumor at diagnosis in new era compared to old era. Conclusion: The new era showed significant changes in the RCC landscape regarding demographic distribution, presentation, and tumor characteristics.

Label-Free SERS of Urine Components: A Powerful Tool for Discriminating Renal Cell Carcinoma through Multivariate Analysis and Machine Learning Techniques.

The advent of Surface-Enhanced Raman Scattering (SERS) has enabled the exploration and detection of small molecules, particularly in biological fluids such as serum, blood plasma, urine, saliva, and tears. SERS has been proposed as a simple diagnostic technique for various diseases, including cancer. Renal cell carcinoma (RCC) ranks as the sixth most commonly diagnosed cancer in men and is often asymptomatic, with detection occurring incidentally. The onset of symptoms typically aligns with advanced disease, aggressive histology, and unfavorable prognosis, and therefore new methods for an early diagnosis are needed. In this study, we investigated the utility of label-free SERS in urine, coupled with two multivariate analysis approaches: Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM), to discriminate between 50 RCC patients and 44 healthy donors. Employing LDA-PCA, we achieved a discrimination accuracy of 100% using 13 principal components, and an 88% accuracy in discriminating between different RCC stages. The SVM approach yielded a training accuracy of 100%, a validation accuracy of 99% for discriminating between RCC and controls, and an 80% accuracy for discriminating between stages. The comparative analysis of raw and normalized SERS spectral data shows that while raw data disclose relative concentration variations in urine metabolites between the two classes, the normalization of spectral data significantly improves the accuracy of discrimination. Moreover, the selection of principal components with markedly distinct scores between the two classes serves to alleviate overfitting risks and reduces the number of components employed for discrimination. We obtained the accuracy of the discrimination between the RCC patients cases and healthy donors of 90% for three PCs and a linear discrimination function, and a 88% accuracy of discrimination between stages using six PCs, mitigating practically the risk of overfitting and increasing the robustness of our analysis. Our findings underscore the potential of label-free SERS of urine in conjunction with chemometrics for non-invasive and early RCC detection.

Abstract 2509: Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors

Abstract The glucocorticoid receptor (GR, or GCR) is a nuclear receptor protein for cortisol and other glucocorticoids and regulates the transcription of thousands of genes involved in metabolism, development, stress, and inflammatory response. In cancer, both an oncogenic and a tumor suppressive function of GR has been proposed. To comprehensively evaluate GR expression in normal and tumorous tissues, a tissue microarray containing 18,570 samples from 147 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). GR positivity was found in 76.3% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity of at least a fraction of tumors was found in all 147 analyzed tumor types and at least one strongly GR positive tumor was found in 136 tumor types. 77 of our 147 tumor entities showed GR positivity of variable intensity in all analyzed cases. 43 further tumor entities showed GR positivity in 80-99.9% of cases. 21 tumor entities had a GR positivity rate between 50 and 80%, including urothelial carcinoma as well as gastric and esophageal adenocarcinoma. Only 6 tumor types had less than 50% GR positive. These included adenomas (21.7-32.5%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum. Reduced GR staining was significantly associated with adverse histopathological and clinical features in several tumor types. Low GR expression was linked to grade progression in pTa (p&amp;lt;0.0001) and to nodal metastasis in pT2-4 urothelial carcinoma of the urinary bladder (p=0.0051), advanced pT stage (p=0.0006) and estrogen receptor positivity (p=0.0126) in breast carcinomas of no special type (NST), as well as to high grade (p≤0.0076), advanced pT stage (p&amp;lt;0.0001), distant metastasis (p=0.0081), and poor overall survival (p=0.002) in clear cell renal cell carcinoma. GR expression was unrelated to clinic-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma as well as in serous high-grade carcinoma of the ovary. In summary, our data demonstrate frequent GR expression across all cancer types. Significant associations between reduced GR expression and unfavorable tumor features in some but not all tumor types suggest that the functional importance of GR regulated genes for cancer progression depends on the cell of tumor origin. Citation Format: Christina Tsourlakis, Frederike Wegener, Katharina Möller, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Christoph Fraune, Natalia Gorbokon, Maximilian Lennartz, Sarah Minner, Florian Viehweger. Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2509.

Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study

The World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of renal cell carcinoma (RCC) is classified from grade 1–4, regardless of subtype. The National Comprehensive Cancer Network (NCCN) guidelines (2022) state that if there is an adverse pathological feature, such as grade 3 or higher RCC in stage 1 patients, more rigorous follow-up imaging is recommended. However, the RCC guidelines do not provide specific treatment or follow-up policies by tumor grade. Therefore, this study attempted to find out whether tumor grade affects survival rates in patients with metastatic RCC. The Korean Renal Cancer Study Group (KRoCS) database includes 3108 patients diagnosed with metastatic RCC between September 1992 and February 2017, with treatment methods, progression, and survival data collected from 11 tertiary hospitals. To obtain information on survival rates or causes of death, we utilized the Korea National Statistical Office database and institutional medical records. Data were accessed for research purpose on June, 2023. We then reviewed these sources to gather comprehensive and reliable data on the outcomes of our study cohort. This database was retrospectively analyzed, and out of 3108 metastatic RCC patients, 911 had been identified as WHO/ISUP grade. Grades were classified into either a low-grade (WHO/ISUP grade 1–2) or a high-grade group (WHO/ISUP grade 3–4). The patients were then analyzed related to progression and overall survival (OS). In metastatic clear cell RCC patients, the 1-year OS rate was 69.4% and the median OS was 17.0 months (15.5–18.5) followed up to 203.6 months. When comparing the patient groups, 119 low-grade and 873 high-grade cases were identified. No baseline difference was observed between the two groups, except that the high-grade group had a higher ECOG 1 ratio of 50.4% compared with 34.5% for the low-grade group (p = 0.009). There was a significant difference in OS between high-grade and low-grade groups. OS was 16.0 months (14.6–17.4) in the high-grade group and 28.0 months (21.1–34.9) in the low-grade group (p < 0.001). However, there was no difference in progression-free survival (PFS) rates with 9.0 months (8.0–10.0) for the high-grade group and 10.0 months (6.8–13.2) for the low-grade group (p = 0.377) in first-line treatment. In multivariable analysis, WHO/ISUP grade was a risk factor (HR = 1.511[1.135–2.013], p = 0.005) that influenced the OS. In conclusion, WHO/ISUP grade is a major data source that can be used as a ubiquitous marker of metastatic RCC in pre-IO era. Depending on whether the RCC is high or low grade, the follow-up schedule will need to be tailored according to grade, with higher-grade patients needing more active treatment as it can not only affect the OS in the previously known localized/locoregional recurrence but also the metastatic RCC patient.