Papillary Renal Cell Carcinoma Research Articles

Pathologic concordance rate and outcomes by histologic subtype in advanced papillary renal cell (pRCC) carcinoma: An analysis from the SWOG S1500 (PAPMET) trial.

4562 Background: The PAPMET trial demonstrated significantly improved progression-free survival (PFS) with cabozantinib vs. sunitinib in advanced pRCC (median: 9.0 vs. 5.6 mos; hazard ratio (HR): 0.60; 95% CI 0.37–0.97). Until recently, pRCC was subclassified as type 1 vs. 2 based on histologic features. During conception of the PAPMET study, we hypothesized that patients with type 1 pRCC will derive more benefit from cabozantinib compared to those with type 2 disease, given enrichment of MET alterations in the former. In this secondary analysis, we report the outcomes stratified by histologic subtype per central review. Methods: Patients with advanced pRCC who had received up to 1 line of therapy were randomized to receive either sunitinib, or cabozantinib, crizotinib or savolitinib stratified by pRCC subtype (type 1, type 2 or not otherwise specified [NOS]). Pathologic data from local pathology review was catalogued. Central pathology review was conducted by 3 expert genitourinary pathologists who independently reviewed tumor specimens. Discordant opinions among these pathologists were individually arbitrated and a unified diagnosis was assigned. Central pathology review results were considered the true positive and the sensitivity, and the positive predictive value (PPV) of local review was estimated for histologic subtypes. Clinical outcomes (objective response rate (ORR) and PFS) were compared between histologic subtypes (by central review) in the cabozantinib and sunitinib arms. Results: Amongst the 147 patients with available local and central pathology review, 17.7% (n=26), 53% (n=78) and 29.3% (n=43) were characterized as having type 1, 2 or NOS/mixed pRCC by local review compared to 29.3% (n=43), 45.6% (n=67) and 25.2% (n=37) respectively by central review. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 49%, type 2: 67% and NOS: 43%) and PPV (type 1: 80%, type 2: 57% and NOS/mixed: 37%) across subtypes. During central review, complete agreement amongst the 3 pathologists was seen in only 33.3% (n=49) of cases and was highest in type 2 tumors (40%; n=27). Compared to sunitinib, cabozantinib demonstrated numerically higher ORR and PFS in both type 1 and type 2 pRCC subgroups. Conclusions: Designation of pRCC subtype by central review did not identify a subset of patients with greater clinical benefit from cabozantinib. Further, classification of subtype was challenged by discordance in both local and central review. Supporting the removal of type 1 and 2 designations from the 2022 WHO guidelines, these findings highlight the limited clinical value and significant challenges associated with subtyping of pRCC. Clinical trial information: NCT02761057 . [Table: see text]

Plasma KIM-1 for preoperative prediction of renal cell carcinoma versus benign renal masses, and association with clinical outcomes.

e16518 Background: For patients with suspicious renal masses, it is often unclear which should receive an intervention versus initial surveillance. Both clear cell and papillary renal cell carcinoma overexpress kidney injury molecule-1 (KIM-1) due to their proximal epithelial cell of origin. We investigated whether plasma KIM-1 improves risk stratification of patients with suspicious kidney masses. Methods: Pre-nephrectomy plasma KIM-1 was measured in two independent cohorts of patients with renal masses. Cohort 1, from the prospective K2 trial, included 162 patients found to have ccRCC (cases) and 162 patients with benign renal masses (controls). Cohort 2 included 247 patients with small (cT1a) renal masses from an academic biorepository. Multivariable models were used to assess the relationship between pre-nephrectomy plasma KIM-1, surgical pathology, and subsequent clinical outcomes. Results: In cohort 1, plasma KIM-1 distinguished RCC versus benign masses with AUC-ROC 0.81 (95% CI: 0.76-0.86). In cohort 2 (cT1a renal masses), plasma KIM-1 distinguished RCC versus benign masses with AUC-ROC 0.74 (95% CI: 0.67 to 0.80). Among patients in cohort 2, the prevalence of malignancy was 97% among patients with the highest quartile of KIM-1 compared to 55% among patients with the lowest quartile of KIM-1. Plasma KIM-1 was higher in clear cell RCC and papillary RCC compared to other histologies (p<0.001 in each cohort). Cohort 1 patients had prospective long-term follow-up, and higher pre-nephrectomy KIM-1 was associated with worse metastasis free survival (multivariable MFS HR 1.29 per unit increase in log KIM-1, 95% CI 1.10-1.53) and worse overall survival (multivariable OS HR 1.31 per unit increase in log KIM-1, 95% CI 1.10-1.54). Conclusions: In two independent cohorts of patients with renal masses, elevated baseline plasma KIM-1 is associated with higher risk of malignant pathology, worse metastasis free survival, and higher risk of death. Plasma KIM-1 may be a useful risk stratification tool for patients with suspicious kidney masses.

Anlotinib combined with sintilimab as first-line treatment in patients with advanced non-clear cell renal cell carcinoma: Preliminary results from an exploratory prospective clinical study.

e16546 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of all kidney cancers, includes papillary RCC, chromophobe RCC, unclassified RCC, and rare entities. Because nccRCC has different molecular characteristics from clear cell carcinoma, drug regimens routinely used for clear cell carcinoma are not very effective in controlling the growth of nccRCC cells. Novel combination regimen of angiogenic inhibitors and immune checkpoint inhibitors has demonstrated significant anti-tumor activity in certain subtypes. The purpose of this trial (NCT05220267) is to evaluate the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor that effectively inhibit VEGFR, FGFR, PDGFR, c-KIT, c-MET and RET) combined with sintilimab (a monoclonal antibody against programmed cell death protein 1) as first-line treatment in patients with advanced nccRCC. Methods: This study is a prospective, single-arm, open-label, phase II clinical trial. Patients aged 18 years or older, without prior systematic treatment, with histologically confirmed advanced nccRCC (defined as TNM staging IV, unresectable locally recurrent or metastatic disease), and ECOG PS 0-1 were considered eligible for enrollment. Patients were treated with oral anlotinib (12 mg once daily on days 1-14, repeated every 21 days) plus intravenous sintilimab (200 mg, once every 3 weeks) till disease progression or intolerant toxicity. The primary endpoint is progression-free survival (PFS) and the secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: Between April 2022 and January 2023, 18 patients (of 13 patients were male) were enrolled (successfully screened and treated with therapeutic regimen at least one time) with a median age of 46 years (range, 18–79). 72.2% of patients had received prior radical nephrectomy and 6% of patients received radiotherapy. PD-L1 expression was determined in 11 patients, of which 5/11(45.5%) had CPS > 1 and 3/11 (27.3%) had CPS > 10. At data cutoff (31 January 2023), 9 patients were evaluable and median (95% CI) follow-up time was 3.7 (0.6-6.8) months, the ORR and DCR were 22.2% (95% CI, 2.8-60.0) and 100% (95% CI, 66.4-100.0), respectively. The median PFS was not reached. The most frequently reported treatment-related adverse events were grade 1 and grade 2 included hand-foot syndrome 55.6%, hyperuricemia 38.9%, proteinuria 33.3%, hoarseness 33.3%, diarrhea 27.8%, hyperthyroidism 27.8%, pharyngitis 27.8%, hypercholesterolemia 27.8%, hyperglycemia 27.8%. Only 4 patients (22.2%) happened grade 2 AEs. No higher grade AEs were observed. Conclusions: Anlotinib combined with sintilimab were preliminary shown promising efficacy with a favourable toxicity profile for patients with advanced nccRCC. Clinical trial information: NCT05220267 .

Metanephric adenoma of kidney: a rare case report

Metanephric adenoma is a rare benign neoplasm of kidney and is usually a differential diagnosis of Wilms tumor (in children) and papillary renal cell carcinoma (in adults). Here, we present a case report of a 40-year-old gentleman with a right renal mass that was ultimately diagnosed by immunohistochemistry of the final specimen after surgery to be a metanephric adenoma. To prevent needless radical nephrectomies in middle-aged patients metanephric adenoma must be considered in the differential diagnosis of renal mass.

Glycolytic regulatory enzyme PFKFB3 as a prognostic and tumor microenvironment biomarker in human cancers.

The 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFK-2/FBPase-2, PFKFB3) is a glycolysis regulatory enzyme and plays a key role in oncogenesis of several cancers. However, the systematic study of crosstalk between PFKFB3 and Tumor microenvironment (TME) in pan-cancer has less been examined. In this study, we conducted a comprehensive analysis of the relationship between PFKFB3 expression, patient prognostic, Tumor mutational burden (TMB), Microsatellite instability (MSI), DNA mismatch repair (MMR), and especially TME, including immune infiltration, immune regulator, and immune checkpoint, across 33 types of tumors using datasets of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). We found that PFKFB3 expression was significantly correlated with patient prognostic and TME factors in various tumors. Moreover, we confirmed that PFKFB3 was an independent prognostic factor for kidney renal papillary cell carcinoma (KIRP), and established a risk prognostic model based on the expression of PFKFB3 as a clinical risk factor, which has a good predictive ability. Our study indicated that PFKFB3 is a potent regulatory factor for TME and has the potential to be a valuable prognostic biomarker in human tumor therapy.

Oncological outcomes of papillary versus clear cell renal cell carcinoma in pT1 and pT2 stage: Results from a contemporary Turkish patient cohort

To compare overall survival (OS), recurrence free survival (RFS), and cancer-specific survival (CSS) in the long-term follow-up of T1 and T2 clear-cell-Renal Cell Carcinoma (ccRCC) and papillary Renal Cell Carcinoma (pRCC) patients, as well as to determine the risk factors for recurrence and overall mortality. Data of patients with kidney tumors obtained from the Urologic Cancer Database - Kidney (UroCaD-K) of Turkish Urooncology Association (TUOA) were evaluated retrospectively. Out of them, patients who had pathological T1-T2 ccRCC and pRCC were included in the study. According to the two histological subtype, recurrence and mortality status, RFS, OS and CSS data were analyzed. RFS, OS and CSS of pRCC and ccRCC were found to be similar. Radiological local invasion was shown to be a risk factor for recurrence in pRCC, and age was the only independent factor affecting overall mortality. There were no differences in survivals (RFS, OS and CSS) of patients with localized papillary and clear cell RCC. While age was the only factor affecting overall mortality, radiological local invasion was a risk factor for recurrence in papillary RCC.

ASPM overexpression enhances cellular proliferation and migration and predicts worse prognosis for papillary renal cell carcinoma

ASPM overexpression enhances cellular proliferation and migration and predicts worse prognosis for papillary renal cell carcinoma

Tumores renales múltiples y hereditarios. Revisión por y para radiólogos

80% of renal carcinomas (RC) are diagnosed incidentally by imaging. 2-4% of “sporadic” multifocality and 5-8% of hereditary syndromes are accepted, probably with underestimation. Multifocality, young age, familiar history, syndromic data, and certain histologies lead to suspicion of hereditary syndrome. Each tumor must be studied individually, with a multidisciplinary evaluation of the patient. Nephron-sparing therapeutic strategies and a radioprotective diagnostic approach are recommended.Relevant data for the radiologist in major RC hereditary syndromes are presented: von-Hippel-Lindau, Chromosome-3 translocation, BRCA-associated protein-1 mutation, RC associated with succinate dehydrogenase deficiency, PTEN, hereditary papillary RC, Papillary thyroid cancer- Papillary RC, Hereditary leiomyomatosis and RC, Birt-Hogg-Dubé, Tuberous sclerosis complex, Lynch, Xp11.2 translocation/TFE3 fusion, Sickle cell trait, DICER1 mutation, Hereditary hyperparathyroidism and jaw tumor, as well as the main syndromes of Wilms tumor predisposition.The concept of “non-hereditary” familial RC and other malignant and benign entities that can present as multiple renal lesions are discussed.

P381 TEAMWORK IS SUCCESSFULL (4): PROGRESSION OF CORONARY ATHEROSCLEROSIS IN A PERIPHERAL T–CELL LYMPHOMA AND PAPILLARY RENAL CELL CARCINOMA SURVIVOR

Abstract Introduction Growing evidence highlight cancer and cardiovascular diseases (CVD) share common risk factors, including genetic ones, and underlying pathogenesis. Such paradigm has significant implications for cancer survivors, an exponential growing cohort of patients (Pts), due to notable improvements in survival achieved with new oncological treatments. However, many new agents of targeted– and immuno–therapy can cause cardiac damage, mainly for vascular involvement, a pathophysiological mechanism different from classic chemotherapeutic agents. We present the case of left ventricular systolic dysfunction (LVSD) in a man with metastatic papillary renal cell carcinoma (PRCC) previously exposed to anthracyclines for former peripheral T–cell lymphoma (PTCL). He came to our attention for cardiological assessment before starting immunotherapy (Nivolumab), due to the failure of Tyrosine kinase inhibitor (TKIs) (Pazopanib) treatment. Clinical case A 74–year–old Pt with hypertension, severe renal dysfunction, dyslipidemia, and exertional dyspnea (NYHA II) presented at transthoracic echocardiogram (TTE) a normal size chambers with mild concentric hypertrophy and a clinically stable moderate LVSD (LVEF 35–40%) at periodic evaluation. Pt was also performing his radiological follow–up for the estimation of metastases with CT, twice a year since 2016. A retrospective review of these non–contrast and non–ECG–gated CT highlighted an extensive increase in coronary artery calcifications during the last four years, started with the beginning of TKIs therapy. In 2018 only mild LAD calcification was detectable (Figure 1), while in 2022 a severe three–vessel coronary atherosclerosis was present (Figure 3). After multi–disciplinary discussion, an aggressive correction of multiple cardiovascular risk factors (starting Rosuvastatin and adjusting Bisoprolol) was performed and immunotherapy started without any adverse event. Conclusions Non–ECG–gated CT routinely performed for monitoring the state of the oncological disease is a useful tool for the evaluation of coronary artery calcific burden and accelerated atherosclerosis. It provides additional information beyond the traditional evaluation of CV risk and must be integrated with clinical and laboratory data.

Sperm protein antigen 17 and Sperm flagellar 1 cancer testis antigens are expressed in a rare case of ciliated foregut cyst of the common hepatic duct

IntroductionCiliated foregut cysts (CFCs) are frequently described in liver, pancreas and gallbladder and generally considered benign although one case of squamous cell metaplasia and five cases of squamous cell carcinoma arising from a ciliated hepatic foregut cyst have been reported. Here we explore two cancer-testis antigens (CTAs), Sperm protein antigen 17 (SPA17) and Sperm flagellar 1 (SPEF1) expression in a rare case of CFC of the common hepatic duct Materials and Methods3 µm-thick CFC sections were immunohistochemically treated with antibodies raised against human SPA17 or SPEF1. In silico Protein-Protein Interaction (PPI) network and differential protein expression were also investigated ResultsImmunohistochemistry revealed SPA17 and SPEF1 in the cytoplasm of ciliated epithelium. SPA17, but not SPEF1, was also detected in cilia. The PPI networks demonstrated that other CTAs are significantly predicted functional partners with SPA17 and SPEF1. The differential protein expression demonstrated that SPA17 was higher in breast cancer, cholangiocarcinoma, liver hepatocellular carcinoma, uterine corpus endometrial carcinoma, gastric adenocarcinoma, cervical squamous cell carcinoma, bladder urothelial carcinoma. SPEF1 expression was higher in breast cancer, cholangiocarcinoma, uterine corpus endometrial carcinoma and kidney renal papillary cell carcinoma ConclusionsOur study suggests that further characterization of SPA17 and SPEF1 in patients with CFCs might provide significant insights to understand the mechanisms underlying their potential to malignant transformation.

Free-Fatty Acid Receptor-4 (FFA4/GPR120) differentially regulates migration, invasion, proliferation and tumor growth of papillary renal cell carcinoma cells

Kidney cancer is among the 10 most common cancers, and renal cell carcinoma (RCC), which represent 90% of all kidney cancers, has the highest mortality rate of all genitourinary cancers. Papillary RCC (pRCC) is the second most frequent subtype of RCC and demonstrates distinct characteristics compared to other subtypes, including a high degree of metastasis and resistance to treatments against the more common clear cell RCC (ccRCC) subtype. Here, we demonstrate that the Free-Fatty Acid Receptor-4 (FFA4), a G protein-coupled receptor that is endogenously activated by medium-to-long chain free-fatty acids, is upregulated in pRCC compared to patient-matched normal kidney tissue, and that the expression of FFA4 increases with the degree of pathological grading of pRCC. Our data also show that FFA4 transcript is not expressed in ccRCC cell lines, but is expressed in the well-characterized metastatic pRCC cell line ACHN. Furthermore, we show that agonism of FFA4 with the selective agonist cpdA positively regulates ACHN cell migration and invasion in a manner dependent on PI3K/AKT/NF-κB signaling to COX-2 and MMP-9, with partial-dependence on EGFR transactivation. Our results also demonstrate that FFA4 agonism induces STAT-3-driven epithelial-mesenchymal transition, suggesting a significant role for FFA4 in pRCC metastasis. On the contrary, FFA4 agonism significantly reduces cell proliferation and tumor growth, suggesting that the receptor may have opposing effects on pRCC cell growth and migration. Together, our data demonstrate that FFA4 has significant functional roles in pRCC cells and may be an attractive target for study of pRCC and development of RCC pharmacotherapeutics.

Minimal Fat Content in Papillary Renal Cell Carcinoma Diagnosed with Dual-Layer Dual-Energy CT.

A 56-year-old man with a previous right nephrectomy for multiple papillary renal cell carcinomas (pRCC) underwent a follow-up CT scan. Using a dual-layer dual-energy CT (dlDECT), we demonstrated the presence of a small amount of fat in a 2.5 cm pRCC that mimicked the diagnosis of angiomyolipoma (AML). Histological examination demonstrated the absence of macroscopic intratumoral adipose tissue, showing a fair amount of enlarged foam macrophages loaded with intracytoplasmic lipids. The presence of fat density in an RCC is an extremely rare occurrence in the literature. To our knowledge, this is the first description using dlDECT of a minimal amount of fat tissue in a small RCC due to the presence of tumor-associated foam macrophages. Radiologists should be aware of this possibility when characterizing a renal mass with DECT. The option of RCCs must be considered, especially in the case of masses with an aggressive character or a positive history of RCC.

The Metastatic Risk of Renal Cell Carcinoma by Primary Tumor Size and Subtype

BackgroundCurrent data on the association between tumor size, subtype, and metastases, and thresholds for intervention, for renal cell carcinoma (RCC), are largely based on single-center nephrectomy registries that may under-represent those presenting with metastatic disease. ObjectiveWe sought to assess tumor size and histologic subtype in relation to metastatic status at presentation for patients with RCC. Design, setting, and participantsUsing Surveillance, Epidemiology and End Results cancer registry data, we identified patients with a diagnosis of RCC made between 2004 and 2019, and a known size of primary tumor. We used nodal and metastatic TNM staging to assess metastatic disease at presentation. Outcome measurements and statistical analysisWe report the proportion of metastatic disease across varying tumor sizes for clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. We also examine sarcomatoid RCC and RCC with sarcomatoid features (sarcRCC). Logistic regression models were used to model the likelihood of metastatic disease for each histologic subtype. Results and limitationsOf 181096 RCC patients included, 23829 had metastatic disease. For any RCC, metastatic rates of 3.6%, 13.1%, 30.3%, and 45.1% were observed for tumors ≤4, 4–≤7, 7–≤10, and >10 cm, respectively. Metastatic rates of chRCC were low at even large sizes, 11.0% at >10 cm. In contrast, sarcRCC had high metastatic rates at all sizes, 27.1% at ≤4 cm. Metastatic rates for ccRCC and pRCC increased steadily above 3 cm. For any RCC and each evaluated subtype, tumor size was found to be associated with metastatic disease on logistic regression (p < 0.001). ConclusionsThe likelihood of a renal mass being metastatic varies greatly with both its subtype and size. We report higher likelihoods of metastatic disease across tumor sizes compared with what has been reported previously. These results may help clinicians pick appropriate thresholds for intervention and candidates for active surveillance. Patient summaryWe find that the metastatic probability of renal cell carcinoma varies greatly with subtype and increases with tumor size.

Renal Cell Carcinoma in the Background of Autosomal Dominant Polycystic Kidney Disease: Report of Two Cases and Review of Literature

AbstractPatients with autosomal dominant polycystic kidney disease (ADPKD), especially those with renal failure, carry a higher risk of developing renal cell carcinoma (RCC) compared to the general population. Genetic mutations associated with ADPKD are known but a direct link associated with RCC is still controversial. We discuss the clinical course of two such patients. The first patient was diagnosed with ADPKD at the age of 10 years with an unreported tubulocystic RCC focus on his renal biopsy that was picked up on review 16 years later when he presented with vertebral metastases determined to have originated from the RCC. He was doing well on multikinase inhibitors till 4 years of diagnosis with metastatic disease when he succumbed to progressive disease after 3 lines of systemic therapy. The second patient was diagnosed with ADPKD in middle age and papillary RCC 3 years later. Within 3 months of cancer diagnosis, there was progression to metastatic disease and rapid decline despite systemic therapies. We surmise that the diagnosis of RCC may be missed in ADPKD till the advanced stages. Patients with ADPKD should be monitored regularly with imaging and biopsy if needed. Histology may be varied but once diagnosed, systemic therapies may help disease control.

Coexistence of multiple clear cell papillary renal cell carcinoma with renal oncocytoma: a case report.

The authors report a case of a female 65-year-old suffering from end-stage kidney failure for 10 years, who presented with a double left renal tumor, composed by an oncocytoma associated to multiple CCPRCC, a very rare entity. A radical left nephrectomy was realized by lumbotomy, with an uneventful postoperative course. Histological examination was challenging. Immunohistological examination showed diffuse positivity of cytokertain 7. No local recurrence nor metastatic progression were found during the 12 months of follow-up. CCPRCC, is a new entity, previously known as the unclassified rena cell carcinoma, is a malignant renal tumor, initially reported in patients at end-stage kidney failure. Oncocytoma is a well-known rare benign renal tumor. The association of both is rare, and should be kept in mind, especially when scanoguided diagnosis biopsy is realized. Histopathological confirmation may be challenging, given the recent identification of CCPRCC. The nuclei disposal toward the luminal surface is a characteristic pathological landmark of CCPRCC. Immunohistopathological examination is of great help, showing a distinctive profile: diffuse staining for cytokertain 7 and carbonic anhydrase IX. CCPRCC is a new malignant pathological entity in renal tumors. It can be associated with other benign renal lesions. This should be taken into consideration while histopathological examination, mainly of scanoguided biopsy cores.

Suburothelial hemorrhage masquerading as renal neoplasms: a case report of antopol Goldman lesion

Renal cell carcinoma (RCC), which accounts for 2-3% of all adult malignancies, is one of the most lethal urologic cancers. They are sporadic in the majority of cases with 4-6% being familial. They are adenocarcinomas arising from renal tubular epithelial cells. They can present with symptoms of loin pain, palpable mass and haematuria. Another rare presentation is spontaneous perirenal haemorrhage which can be seen in up to 50% of these patients. These patients are also predisposed to increased risk of deep vein thrombosis (DVT) due to prevailing pro-thrombogenic state. Management requires radical nephrectomy for localised disease, targeted therapy and cytoreductive nephrectomy for metastatic RCC. Our patient is adult female who was referred to surgical OPD given her history of gross haematuria and right flank pain for 6 days. She is a known case of DVT on treatment with Warfarin for 4 years. A diagnosis of renal malignancy was made, contrast CT was suggestive of solid mass lesion of the upper pole of calyx likely transitional cell carcinoma (TCC)/papillary RCC. She underwent an urgent radical nephrectomy which showed a hard 5×5 cm lump in the upper pole of the kidney, revealing a clot on the cut section. Post-op HPE showed a large subcapsular hematoma in the upper pole with microscopy showing large areas of haemorrhage surrounded by chronic inflammatory infiltrate, likely Antopol Goldman lesion notorious for its similarity to renal malignancy.

Network diffusion-based approach for survival prediction and identification of biomarkers using multi-omics data of papillary renal cell carcinoma

Identification of cancer subtypes based on molecular knowledge is crucial for improving the patient diagnosis, prognosis, and treatment. In this work, we integrated copy number variations (CNVs) and transcriptomic data of Kidney Papillary Renal Cell Carcinoma (KIRP) using a network diffusion strategy to stratify cancers into clinically and biologically relevant subtypes. We constructed GeneNet, a KIRP specific gene expression network from RNA-seq data. The copy number variation data was projected onto GeneNet and propagated on the network for clustering. We identified robust subtypes that are biologically informative and significantly associated with patient survival, tumor stage and clinical subtypes of KIRP. We performed a Singular Value Decomposition (SVD) analysis of KIRP subtypes, which revealed the genes/silent players related to poor survival. A differential gene expression analysis between subtypes showed that genes related to immune, extracellular matrix organization, and genomic instability are upregulated in the poor survival group. Overall, the network-based approach revealed the molecular subtypes of KIRP and captured the relationship between gene expression and CNVs. This framework can be further expanded to integrate other omics data.

Renal Tumours Of Non-Clear Cell Histology; 10 Years' Experience In A Specialized Centre.

Non-clear cell renal cell carcinomas are uncommon renal tumours with diverse histologically and genetically defined entities. Due to limited clinical outcomes data, no standardized management approach can be offered to these patients. This study aimed to analyse outcomes of non clear cell renal cell carcinoma after surgical resection of localized renal tumours in our population. Patients with renal tumours who underwent partial or radical nephrectomy at the Department of Urology, from January 2010 to December 2019 were identified and evaluated, in terms of prevalence, presentation, recurrence, and survival outcome. Non-clear cell tumours were found in one-fourth of the total number of nephrectomies performed during this period for renal cell carcinoma (RCC). The mean age was 50.48±14.76 years (range 18-89 years) with 57% being of the male gender. The predominant types were chromophobe RCC, papillary RCC, and sarcomatoid RCC, in all non-clear cell renal tumours. Mean Recurrence Free Survival (RFS) for all tumours was 75.26±2.7 months. The projected 5 years RFS of papillary RCC, chromophobe RCC and sarcomatoid RCC were 94.2%, 84.3% and 62.5% respectively. RCC of non-clear-cell histology depicts excellent survival in patients with localized renal tumours. Furthermore, sarcomatoid RCC has worse recurrence free survival followed by chromophobe RCC and papillary RCC, in our population subset.

Clinicopathologic Classification of Renal Cell Carcinoma in Patients ≤40 Years Old From Peru.

There are scant data on renal cell carcinoma (RCC) from relatively younger patients in South America using contemporary classification. Fifty-nine consecutively treated patients with RCC (≤40 years old) were assessed from the National Institute of Neoplastic Diseases in Peru from 2008 to 2020 (34 males; 25 females), age range of 13 to 40 years. Most common presenting symptoms were flank pain (n = 40), hematuria (n = 19), and weight loss (n = 12). Associated conditions included 4 patients with proven or presumed tuberous sclerosis and 1 patient with von Hippel Lindau syndrome, all with clear cell RCC. Tumor histopathology was clear cell RCC in 32 of 59 (54%), chromophobe RCC in 6 of 59 (10%), and 5 of 59 (8%) each of papillary RCC and MiT family translocation-associated RCC. Four of 59 (7%) were FH-deficient RCC and 2 of 59 (3%) remained unclassified. The remaining tumors were isolated examples of clear cell papillary renal cell tumor, eosinophilic solid and cystic RCC (ESC RCC), RCC with fibromyomatous stroma, sarcomatoid RCC, and sarcomatoid clear cell RCC. Of the 4 FH-deficient RCCs, none had the classic morphology. The 5 MiT family translocation RCCs had variable morphology. There were 41 tumors without recurrence or metastases, 3 tumors with local recurrence only, 8 tumors with metastases only, and 7 tumors with both local recurrence and metastases. The current study demonstrates the importance of special studies in accurately classifying RCC in younger individuals. The distribution of RCC subtypes in younger individuals is similar between 2 representative large institutions of the United States and Peru.

Identification and verification of prognostic cancer subtype based on multi-omics analysis for kidney renal papillary cell carcinoma.

Identifying Kidney Renal Papillary Cell Carcinoma (KIRP) patients with high-risk, guiding individualized diagnosis and treatment of patients, and identifying effective prognostic targets are urgent problems to be solved in current research on KIRP. In this study, data of multi omics for patients with KIRP were collected from TCGA database, including mRNAs, lncRNAs, miRNAs, data of methylation, and data of gene mutations. Data of multi-omics related to prognosis of patients with KIRP were selected for each omics level. Further, multi omics data related to prognosis were integrated into cluster analysis based on ten clustering algorithms using MOVICS package. The multi omics-based cancer subtype (MOCS) were compared on biological characteristics, immune microenvironmental cell abundance, immune checkpoint, genomic mutation, drug sensitivity using R packages, including GSVA, clusterProfiler, TIMER, CIBERSORT, CIBERSORT-ABS, quanTIseq, MCPcounter, xCell, EPIC, GISTIC, and pRRophetic algorithms. The top ten OS-related factors for KIRP patients were annotated. Patients with KIRP were divided into MOCS1, MOCS2, and MOCS3. Patients in the MOCS3 subtype were observed with shorter overall survival time than patients in the MOCS1 and MOCS2 subtypes. MOCS1 was negatively correlated with immune-related pathways, and we found global dysfunction of cancer-related pathways among the three MOCS subtypes. We evaluated the activity profiles of regulons among the three MOCSs. Most of the metabolism-related pathways were activated in MOCS2. Several immune microenvironmental cells were highly infiltrated in specific MOCS subtype. MOCS3 showed a significantly lower tumor mutation burden. The CNV occurrence frequency was higher in MOCS1. As for treatment, we found that these MOCSs were sensitive to different drugs and treatments. We also analyzed single-cell data for KIRP. Based on a variety of algorithms, this study determined the risk classifier based on multi-omics data, which could guide the risk stratification and medication selection of patients with KIRP.