Showing papers on "Papillary renal cell carcinomas published in 2021"

Papillary renal cell carcinoma: Review.

Abstract: Kidney cancer is the 13th most common malignancy globally, and the incidence is rising. Papillary renal cell carcinoma is the second most common subtype, comprising 10-15% of renal cell carcinomas. Though the histologic features of this subtype were initially described in the 1990's, our understanding of the genetic and molecular characteristics of this disease have rapidly evolved over the past decade. In this review, we summarize the contemporary understanding of the clinical, morphologic, radiographic, and genetic characteristics of papillary renal cell carcinoma, as well as clinical considerations, current options for management, and prognosis.

Modest efficacy of nivolumab plus ipilimumab in patients with papillary renal cell carcinoma

Abstract: Purpose Combined immunotherapy of nivolumab plus ipilimumab for intermediate- and poor-risk metastatic clear cell renal cell carcinoma showed prolonged progression-free survival and high objective response rate in a randomized phase III clinical trial. However, the efficacy of this treatment for papillary renal cell carcinoma remains unclear. In the present study, we analysed the efficacy of nivolumab plus ipilimumab therapy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Materials and methods This is a retrospective study of 30 patients with metastatic renal cell carcinoma who received nivolumab and ipilimumab as first-line therapy between December 2015 and May 2020. The objective response rate, progression-free survival and toxicity were compared between the two groups (clear cell renal cell carcinoma and papillary renal cell carcinoma). Results Out of 30 patients, 7 and 23 were diagnosed with papillary renal cell carcinoma and clear cell renal cell carcinoma, respectively. With a median follow-up of 7.2 months, the median progression-free survival was significantly shorter in papillary renal cell carcinoma than in clear cell renal cell carcinoma (2.4 vs. 28.1 months, P = 0.014). Of the seven patients with papillary renal cell carcinoma, one had partial response, one had stable disease and five had progressive disease, resulting in an objective response rate of 14.2%, which was lower compared to that of clear cell renal cell carcinoma (14.2 vs. 52.1%, P = 0.06). Discontinuation due to toxicity was not observed with papillary renal cell carcinoma, meanwhile 60.8% of patient with clear cell renal cell carcinoma discontinued treatment due to toxicity. Conclusion Nivolumab plus ipilimumab had modest efficacy for papillary renal cell carcinoma compared with that for clear cell renal cell carcinoma. Nivolumab plus ipilimumab remains an option for a limited number of patients with intermediate- or poor-risk papillary renal cell carcinoma.

Clinicopathological and molecular characterisation of papillary renal neoplasm with reverse polarity and its renal papillary adenoma analogue.

Abstract: AIMS Papillary renal neoplasm with reverse polarity (PRNRP) is a newly defined entity with distinct histomorphology and recurrent KRAS mutation. It has been estimated to constitute 4% of previously diagnosed papillary renal cell carcinoma (PRCC). Renal papillary adenoma (PA) is suggested to be the precursor of PRCC. This study aimed to investigate the association between PRNRP and PA, particularly the morphologically similar type D PA. METHODS AND RESULTS Nephrectomy specimens of PRCC and PA from our 10-year pathology archives were retrieved and reviewed. GATA3 immunohistochemistry and RAS/BRAF testing were performed in all cases reclassified as PRNRP and all PAs with sufficient materials. Overall, PRNRP accounted for 9.1% (10 of 110) of PRCC and there was no recurrence/metastasis with a mean follow-up period of 39 months. Three novel morphological features were described, including clear cell change, mast cell infiltration and metaplastic ossification. Nine of the 10 PRNRPs showed diffuse and strong GATA3 expression and KRAS missense mutations at codon 12. One case exhibited moderate GATA3 staining on 80% of the tumour cells and RAS/BRAF wild-type. In a total of 73 PAs, 11 were classified as type D. GATA3 expression was significantly more frequent in type D versus non-type D PAs (100 versus 35%, P < 0.01). KRAS missense mutations were identified in six of eight (75%) of the type D PAs but none of the 18 non-type D PAs. CONCLUSIONS Type D PA was different from other types of PA and represented an analogue or a small-sized PRNRP for their identical morphology, immunophenotype and molecular signature.

A Review of Recent Research on the Role of MicroRNAs in Renal Cancer.

Abstract: Renal cell carcinoma (RCC) is a most common type of urologic neoplasms; it accounts for 3% of malignant tumors, with high rates of relapse and mortality. The most common types of renal cancer are clear cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal carcinoma (chRCC), which account for 90%, 6-15%, and 2-5%, respectively, of all renal malignancies. Although surgical resection, chemotherapy, and radiotherapy are the most common treatment method for those diseases, their effects remain dissatisfactory. Furthermore, recent research shows that the treatment efficacy of checkpoint inhibitors in advanced RCC patients is widely variable. Hence, patients urgently need a new molecular biomarker for early diagnosis and evaluating the prognosis of RCC. MicroRNAs (miRNAs) belong to a family of short, non-coding RNAs that are highly conserved, have long half-life evolution, and post-transcriptionally regulate gene expression; they have been predicted to play crucial roles in tumor metastasis, invasion, angiogenesis, proliferation, apoptosis, epithelial-mesenchymal transition, differentiation, metabolism, cancer occurrence, and treatment resistance. Although some previous papers demonstrated that miRNAs play vital roles in renal cancer, such as pathogenesis, diagnosis, and prognosis, the roles of miRNAs in kidney cancer are still unclear. Therefore, we reviewed studies indexed in PubMed from 2017 to 2020, and found several studies suggesting that there are more than 82 miRNAs involved in renal cancers. The present review describes the current status of miRNAs in RCC and their roles in progression, diagnosis, therapy targeting, and prognosis of RCC.

Anti-tumor efficacy of human anti-c-met CAR-T cells against papillary renal cell carcinoma in an orthotopic model.

Abstract: Chimeric antigen receptor (CAR)-T cell therapy has shown salient efficacy in cancer immunotherapy, particularly in the treatment of B cell malignancies. However, the efficacy of CAR-T for solid tumors remains inadequate. In this study, we displayed that c-met is an appropriate therapeutic target for papillary renal cell carcinoma (PRCC) using clinical samples, developed an anti-human c-met CAR-T cells, and investigated the anti-tumor efficacy of the CAR-T cells with an orthotopic mouse model as a pre-clinical research. Administration of the anti-c-met CAR-T cells induced remarkable infiltration of the CAR-T cells into the tumor tissue and unambiguous suppression of the tumor growth. Furthermore, in combination with axitinib, the anti-tumor efficacy of the CAR-T cells was synergistically augmented. Taken together, our current study demonstrated the potential for clinical application of anti-c-met CAR-T cells in the treatment of patients with PRCC.

The Morphological Spectrum of Papillary Renal Cell Carcinoma and Prevalence of Provisional/Emerging Renal Tumor Entities with Papillary Growth.

Abstract: Renal cell carcinoma (RCC) represents a heterogeneous disease, encompassing an increasing number of tumor subtypes. Post-2016, the World Health Organization (WHO) classification recognized that the spectrum of papillary renal cell carcinoma is evolving and has long surpassed the dichotomic simplistic “type 1 versus type 2” classification. The differential diagnosis of pRCC includes several new provisional/emerging entities with papillary growth. Type 2 tumors have been cleared out of several confounding entities, now regarded as independent tumors with specific clinical and molecular backgrounds. In this work we describe the prevalence and characteristics of emerging papillary tumor entities in two renal tumor cohorts (one consisting of consecutive papillary tumors from a single institute, the other consisting of consultation cases from several centers). After a review of 154 consecutive pRCC cases, 58% remained type 1 pRCC, and 34% type 2 pRCC. Papillary renal neoplasm with reversed polarity (1.3%), biphasic hyalinizing psammomatous RCC (1.3%), and biphasic squamoid/alveolar RCC (4.5%) were rare. Among 281 consultation cases, 121 (43%) tumors had a dominant papillary growth (most frequently MiT family translocation RCCs, mucinous tubular and spindle cell carcinoma and clear cell papillary RCC). Our data confirm that the spectrum of RCCs with papillary growth represents a major diagnostical challenge, frequently requiring a second expert opinion. Papillary renal neoplasm with reversed polarity, biphasic hyalinizing psammomatous RCC, and biphasic squamoid/alveolar RCC are rarely sent out for a second opinion, but correct classification and knowledge of these variants will improve our understanding of the clinical behavior of renal tumors with papillary growth.

NF2 Tumor Suppressor Gene Inactivation in Advanced Papillary Renal Cell Carcinoma.

Abstract: To the Editor: In a recent issue of this journal, Argani et al1 described a distinctive biphasic hyalinizing psammomatous renal cell carcinoma (RCC) associated with somatic neurofibromatosis type 2 (NF2) gene mutations. We would like to support the observation of Argani and colleagues by providing molecular evidence of NF2 mutation-associated renal neoplasia in a large cohort of clinically advanced papillary renal cell carcinomas (pRCCs) and highlight the importance of this finding for the application of targeted therapies. The NF2 gene on chromosome 22q encodes the tumor suppressor protein merlin involved in a wide range of mitogenic signaling pathways, including receptor tyrosine kinases, Rac/p21-activated kinase, mammalian/ mechanistic target of rapamycin (mTOR), and the Hippo pathway. Heterozygous germline NF2 loss or inactivation is associated with neurofibromatosis type 2 syndrome, which results in the development of vestibular schwannomas, meningiomas, ependymomas, and ocular disturbances. Somatic genomic alterations (GAs) in NF2 have recently been described in a spectrum of kidney tumors including aggressive variants such as collecting duct carcinoma, sarcomatoid RCC, and unclassified RCC as well as in more indolent mucinous and spindle cell carcinoma of the kidney.2–5 We analyzed NF2 GA by comprehensive genomic profiling (CGP) in a large cohort of 414 clinically advanced pRCCs to evaluate (1) the frequencies and type of NF2 GA; and (2) cooccurring GA in other genes and biomarkers to support the driving role of NF2. Formalin-fixed paraffin-embedded tissues underwent hybrid-capture based CGP using the FoundationOne platform which interrogates the coding exons of up to 395 cancer-related genes and introns from up to 34 genes commonly rearranged in cancer (Cambridge, MA) to evaluate all classes of GA, variant-level loss of heterozygosity (LOH), tumor mutational burden (TMB), and microsatellite instability. Programmed death-ligand 1 (PD-L1) (Dako 22C3) and NF2 (1:100, D3S3W; Cell Signalling Technology) expression in tumor cells was measured by immunohistochemistry (IHC). Forty-eight (12%) pRCC cases featured NF2 GA. All NF2 mutant (NF2mut) cases were stage IV; 21 NF2mut samples used for CGP were biopsies of metastases and 27 were primary kidney tumors. The age and sex were not statistically different between NF2mut and NF2 wild-type (NF2wt) pRCCs (Table 1). Notable differences of our cohort from the TCGA pRCC dataset include a higher incidence of NF2 GA (12% vs. 3.2%). In contrast to the limited number of patients with confirmed stage IV disease in the TCGA cohort, the majority of patients in our cohort had stage IV disease. Thus, higher frequencies of NF2 GA in our cohort suggest an association ofNF2GA with more aggressive pRCC and may suggest its role in disease progression. The distribution of GA in pRCC is shown in the Table 1 and Supplementary Figure 1 (Supplemental Digital Content 1, http://links.lww.com/PAS/B12). Within NF2muts, short variant (SV) mutations were the predominant type of GA (76.4%). Less common GA were copy number alterations (homozygous deletions and amplifications) (12.7% and TABLE 1. Clinicopathologic Features and GAs in NF2 Mutated Versus NF2 Wildtype pRCC

Y-chromosome loss is frequent in male renal tumors

Abstract: Background Loss of the Y-chromosome is a common event in different tumor types but its prevalence and clinical relevance in renal cell tumors is still not understood. Methods It was the aim of this study to estimate the frequency and clinical relevance of Y-loss in kidney neoplasms. A cohort of 1,252 male renal tumors was analyzed in a tissue microarray format by fluorescence in-situ hybridization (FISH). Results Y-loss was found in 47% of tumors. The frequency of this alteration varied markedly between kidney tumor subtypes. Y-loss was most prevalent in papillary renal cell carcinoma (RCC) (77%) followed by chromophobe RCC (60%), oncocytoma (51%), clear cell RCC (39%) and clear cell (tubulo)papillary RCC (19%). Y-loss was linked to higher patient age and smaller tumor size at diagnosis. Mean age (95% CI) was 65 (64-66) years in patients with Y-loss in their tumor compared to 60 (58-61) years in patients without Y-loss (P<0.0001). Significant correlations between Y-loss and tumor phenotype were found only for papillary carcinomas (P=0.002), especially for type 1 (P=0.03). Conclusions Y-loss is present in different histologic subtypes of renal neoplasm. The highest frequency is in papillary RCC, where it may represent a potentially relevant prognostic biomarker suggesting favorable disease outcome.

Characterization of genetically defined sporadic and hereditary type 1 papillary renal cell carcinoma cell lines.

Abstract: Renal cell carcinoma (RCC) is not a single disease but is made up of several different histologically defined subtypes that are associated with distinct genetic alterations which require subtype specific management and treatment Papillary renal cell carcinoma (pRCC) is the second most common subtype after conventional/clear cell RCC (ccRCC), representing ~20% of cases, and is subcategorized into type 1 and type 2 pRCC It is important for preclinical studies to have cell lines that accurately represent each specific RCC subtype This study characterizes seven cell lines derived from both primary and metastatic sites of type 1 pRCC, including the first cell line derived from a hereditary papillary renal carcinoma (HPRC)-associated tumor Complete or partial gain of chromosome 7 was observed in all cell lines and other common gains of chromosomes 16, 17, or 20 were seen in several cell lines Activating mutations of MET were present in three cell lines that all demonstrated increased MET phosphorylation in response to HGF and abrogation of MET phosphorylation in response to MET inhibitors CDKN2A loss due to mutation or gene deletion, associated with poor outcomes in type 1 pRCC patients, was observed in all cell line models Six cell lines formed tumor xenografts in athymic nude mice and thus provide in vivo models of type 1 pRCC These type 1 pRCC cell lines provide a comprehensive representation of the genetic alterations associated with pRCC that will give insight into the biology of this disease and be ideal preclinical models for therapeutic studies

Napsin A Expression in Human Tumors and Normal Tissues

Abstract: Background: Novel aspartic proteinase of the pepsin family A (Napsin A, TAO1/TAO2) is a functional aspartic proteinase which is involved in the maturation of prosurfactant protein B in type II pneumocytes and the lysosomal protein catabolism in renal cells. Napsin A is highly expressed in adenocarcinomas of the lung and is thus commonly used to affirm this diagnosis. However, studies have shown that other tumors can also express Napsin A. Methods: To comprehensively determine Napsin A expression in normal and tumor tissue, 11,957 samples from 115 different tumor types and subtypes as well as 500 samples of 76 different normal tissue types were evaluable by immunohistochemistry on tissue microarrays. Results: Napsin A expression was present in 16 different tumor types. Adenocarcinoma of the lung (85.6%), clear cell adenocarcinoma of the ovary (71.7%), clear cell adenocarcinoma of the endometrium (42.8%), papillary renal cell carcinoma (40.2%), clear cell (tubulo) papillary renal cell carcinoma (16.7%), endometrial serous carcinoma (9.3%), papillary thyroid carcinoma (9.3%) and clear cell renal cell carcinoma (8.2%) were among the tumors with the highest prevalence of Napsin A positivity. In papillary and clear cell renal cell carcinoma, reduced Napsin A expression was linked to adverse clinic-pathological features (p ≤ 0.03). Conclusion: This methodical approach enabled us to identify a ranking order of tumors according to their relative prevalence of Napsin A expression. The data also show that loss of Napsin A is linked to tumor dedifferentiation in renal cell carcinomas.

Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma: Another Provisional Entity Emerging From the Papillary Renal Cell Carcinoma Pandora's Box:

Abstract: Papillary renal cell carcinoma (especially type 2) is a Pandora's box with many newly described renal cell carcinomas emerging from it as a result of enhanced molecular techniques. Biphasic hyalini...

Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study.

Abstract: 270Background: MET signaling is a key molecular driver in pRCC. Given that there is no optimal therapy for metastatic pRCC, we sought to compare an existing standard (sunitinib) to putative MET kin...

Metanephric adenoma with BRAF V600K mutation and a doubtful radiological imaging: pitfalls in the diagnostic process

Abstract: Metanephric adenoma (MA) is an uncommon benign renal tumor whose histomorphological aspect resembles that of Wilms' tumor and papillary renal cell carcinoma. From a diagnostic and therapeutic perspective, recognition of this entity is important as it has a more favorable clinical outcome compared with Wilms' tumor and papillary renal cell carcinoma. MA should not be treated with nephrectomy if the tumor size is small, opting for a conservative treatment. However, the preoperative diagnosis of this disease is extremely challenging. The present study describes a case of this rare disease, showing an ambiguous radiological imaging and that only after a percutaneous biopsy, was defined as a MA and treated with partial nephrectomy. Moreover, the histological diagnosis of this case was partially complicated by the equivocal immunohistochemical analysis showing negativity for BRAF VE1 staining. Only the mutational analysis demonstrated the presence of the BRAF V600K mutation (for the first time described in a case of metanephric adenoma), highlighting the necessity of sequencing in case of MA with negativity for BRAF VE1 clone.

Deep learning with a convolutional neural network model to differentiate renal parenchymal tumors: a preliminary study.

Abstract: With advancements in medical imaging, more renal tumors are detected early, but it remains a challenge for radiologists to accurately distinguish subtypes of renal parenchymal tumors. We aimed to establish a novel deep convolutional neural network (CNN) model and investigate its effect on identifying subtypes of renal parenchymal tumors in T2-weighted fat saturation sequence magnetic resonance (MR) images. This retrospective study included 199 patients with pathologically confirmed renal parenchymal tumors, including 77, 46, 34, and 42 patients with clear cell renal cell carcinoma (ccRCC), chromophobe renal cell carcinoma (chRCC), angiomyolipoma (AML), and papillary renal cell carcinoma (pRCC), respectively. All enrolled patients underwent kidney MR scans with the field strength of 1.5 Tesla (T) or 3.0 T before surgery. We selected T2-weighted fat saturation sequence images of all patients and built a deep learning model to determine the type of renal tumors. Receiver operating characteristic (ROC) curve was depicted to estimate the performance of the CNN model; the accuracy, precision, sensitivity, specificity, F1-score, and area under the curve (AUC) were calculated. One-way analysis of variance and χ2 tests of independent samples were used to analyze the variables. The experimental results demonstrated that the model had a 60.4% overall accuracy, a 61.7% average accuracy, and a macro-average AUC of 0.82. The AUCs for ccRCC, chRCC, AML, and pRCC were 0.94, 0.78, 0.80, and 0.76, respectively. Deep CNN model based on T2-weighted fat saturation sequence MR images was useful to classify the subtypes of renal parenchymal tumors with a relatively high diagnostic accuracy.

Tumor-to-Tumor Metastasis: Lung Adenocarcinoma as a Recipient of Metastasis from Renal Cell Carcinoma: A Case Report.

Abstract: BACKGROUND The occurrence of metastasis from one neoplasm to another is known as tumor-to-tumor metastasis (TTM). It is a rare phenomenon in the natural history of any neoplasm, with approximately 100 cases reported in the literature to date. The lungs are the most frequent metastatic tumor donors and kidney cancer is the most common recipient. However, the opposite phenomenon (lung adenocarcinoma as a recipient of metastasis from renal carcinoma) has not been previously reported in the literature. CASE REPORT We present the case of a man with a history of multiple neoplasms. He had a diffuse large B-cell lymphoma in 2006, a left papillary renal cell carcinoma (RCC) type 2 in 2006, and an acinar adenocarcinoma of the prostate in 2011. A follow-up computed tomography scan in July 2019 showed a suspicious lung nodule on the left upper lobe and a retroperitoneal hypermetabolic mass on the positron emission tomography scan. The lung nodule and retroperitoneal mass biopsies were consistent with a primary lung adenocarcinoma with a lepidic pattern and a metastatic RCC, respectively. In January 2020, he underwent a thoracoscopic left upper lobectomy and a mediastinal lymph node dissection. Histopathological evaluation revealed a 2-cm nodule composed of a lung adenocarcinoma with an intratumoral metastasis from a papillary RCC. To date, the patient has stable renal neoplastic metastatic disease and no locoregional recurrences of the lung adenocarcinoma. CONCLUSIONS Metastasis from one primary tumor to another primary tumor is an extremely unusual event. We report one of the first cases of an RCC metastasis to a primary lung adenocarcinoma.

Increased Expression of TICRR Predicts Poor Clinical Outcomes: A Potential Therapeutic Target for Papillary Renal Cell Carcinoma.

Abstract: Background: Papillary renal cell carcinoma (PRCC), although the second-most common type of renal cell carcinoma, still lacks specific biomarkers for diagnosis, treatment, and prognosis. TopBP1-interacting checkpoint and replication regulator (TICRR) is a DNA replication initiation regulator upregulated in various cancers. We aimed to evaluate the role of TICRR in PRCC tumorigenesis and prognosis. Methods: Based on the Kidney Renal Papillary cell carcinoma Project (KIRP) on The Cancer Genome Atlas (TCGA) database, we determined the expression of TICRR using the Wilcoxon rank sum test. The biological functions of TICRR were evaluated using the Metascape database and Gene Set Enrichment Analysis (GSEA). The association between TICRR and immune cell infiltration was investigated by single sample GSEA. Logistic analysis was applied to study the correlation between TICRR expression and clinicopathological characteristics. Finally, Cox regression analysis, Kaplan–Meier analysis, and nomograms were used to determine the predictive value of TICRR on clinical outcomes in PRCC patients. Results: TICRR expression was significantly elevated in PRCC tumors (P < 0.001). Functional annotation indicated enrichment with negative regulation of cell division, cell cycle, and corresponding pathways in the high TICRR expression phenotype. High TICRR expression in PRCC was associated with female sex, younger age, and worse clinical stages. Cox regression analysis revealed that TICRR was a risk factor for overall survival [hazard ratio (HR): 2.80, P = 0.002], progression-free interval (HR: 2.86, P < 0.001), and disease-specific survival (HR: 7.03, P < 0.001), especially in patients with male sex, age below 60 years, clinical stages II–IV and clinical T stage T1–T2. Conclusion: Increased TICRR expression in PRCC might play a role in tumorigenesis by regulating the cell cycle and has prognostic value for clinical outcomes.

A Case of Low-Grade Oncocytic Tumor/Chromophobe Renal Cell Carcinoma (Oncocytic Variant) of the Kidney.

Abstract: The oncocytic variant of chromophobe renal cell carcinoma (oChRCC) and low-grade oncocytic tumor (LOT) is introduced as new renal disease entity. Both of these tumors are low-grade malignancies consisting of cells with eosinophilic cytoplasm. Distinguishing between eosinophilic variant of chromophobe renal cell carcinoma (eCRCC) and oncocytoma is often a diagnostic challenge in routine surgical pathology. However, oChRCC and LOT might be independent disease entities that might not fit completely into any of these categories. Histologically, these tumors have greater morphological similarity with oncocytoma than with ChRCC. However, immunohistochemically, they exhibit diffuse and dense positivity for CK7 and are negative for CD117. In the present case, we initially had difficulty distinguishing among oncocytoma, eCRCC, and type 2 papillary renal cell carcinoma (2-pRCC). However, after learning about new disease entities such as oChRCC and LOT, we were able to diagnose this tumor.

Tissue based biomarkers in non-clear cell RCC: Correlative analysis from the ASPEN clinical trial

Abstract: Biomarkers are needed in patients with non-clear cell renal cell carcinomas (NC-RCC), particularly papillary renal cell carcinoma, in order to inform on initial treatment selection and identify potentially novel targets for therapy. We enrolled 108 patients in ASPEN, an international randomized open-label phase 2 trial of patients with metastatic papillary, chromophobe, or unclassified NC-RCC treated with the mTOR inhibitor everolimus (n=57) or the vascular endothelial growth factor (VEGF) receptor inhibitor sunitinib (n=51), stratified by MSKCC risk and histology. The primary endpoint was overall survival (OS) and secondary efficacy endpoints for this exploratory biomarker analysis were radiographic progression-free survival (rPFS) defined by intention-to-treat using the RECIST 1.1 criteria and radiographic response rates. Tissue biomarkers (n=78) of mTOR pathway activation (phospho-S6 and -Akt, c-kit) and VEGF pathway activation (HIF-1α, c-MET) were prospectively explored in tumor tissue by immunohistochemistry prior to treatment and associated with clinical outcomes. We found that S6 activation was more common in poor risk NC-RCC tumors and S6/Akt activation was associated with worse PFS and OS outcomes with both everolimus and sunitinib, while c-kit was commonly expressed in chromophobe tumors and associated with improved outcomes with both agents. C-MET was commonly expressed in papillary tumors and was associated with lower rates of radiographic response but did not predict PFS for either agent. In multivariable analysis, both pAkt and c-kit were statistically significant prognostic biomarkers of OS. No predictive biomarkers of treatment response were identified for clinical outcomes. Most biomarker subgroups had improved outcomes with sunitinib as compared to everolimus.

Malignant ascites following radical nephrectomy for cystic renal cell carcinoma.

Abstract: A 69-year-old man with a history of laparoscopic radical nephrectomy for papillary renal cell carcinoma presented with a 1-week history of generalised abdominal pain, distension and loss of appetite. Clinical examination and CT imaging demonstrated ascites associated with peritoneal nodules, raising the possibility of metastatic disease. Immunochemistry staining from ascites fluid cytology confirmed renal cell carcinoma. Following multidisciplinary discussions, the patient was commenced on a small-molecule tyrosine kinase inhibitor.

Characterizing the tumor microenvironment in rare renal cancer histological types.

Abstract: The tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann-Whitney and Kruskal-Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53-4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22-5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42-3.9]). Spatial analysis revealed CD3+ T-cell and CD20+ B-cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance-dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.

PTP4A3 Is a Prognostic Biomarker Correlated With Immune Infiltrates in Papillary Renal Cell Carcinoma.

Abstract: PTP4A3 plays an important role in the tumorigenesis and metastasis of multiple tumors, but its prognostic role in renal cancer is not well understood. We utilized the Oncomine and Tumor Immunoassay Resource databases to examine the differential expression of PTP4A3 in tumor tissues and normal tissues in breast, urinary tract, gastrointestinal tract and skin. Using the GEPIA and PrognoScan databases, the independent prognostic role of PTP4A3 was confirmed in clear cell renal cell cancer and papillary renal cell cancer. Expression of PTP4A3 were obviously higher in tumor tissue compare with normal tissues (P=0.028). We haven't found the associations of PTP4A3 and clinicopathological features in our IHC cohort. Ectopic expression of PTP4A3 promotes proliferation, migration and invasion and increased the mRNA level of TGFB1 in RCC cell lines. Immunohistochemical staining indicated that the expression of PTP4A3 associates with CD3+ (P =0.037)/CD8+ (P =0.037) intratumor TILs, not with invasive margins in renal cancer. Comprehensive analysis of immune infiltration in the TIMER database correlated PTP4A3 expression with the infiltration of B cells, CD8+ T cells, CD4+ T cells and neutrophils in both clear cell renal cell carcinoma and papillary renal cell carcinoma. PTP4A3 expression was associated with the infiltration of dendritic cells in papillary renal cell carcinoma. We further confirmed that the infiltration of B cells and CD8+ T cells was associated with poor prognosis in papillary renal cell carcinoma patients, consistent with the prognostic role of PTP4A3 in papillary renal cell carcinoma. PTP4A3 expression correlated genes involved in B cells, monocytes, M1 macrophages, Th2 and Treg cells in papillary renal cell carcinoma. These results suggest PTP4A3 as a prognostic factor with a role in regulating immune cell infiltration in papillary renal cell carcinoma.

Integrative Analysis of Immune-Related Genes in the Tumor Microenvironment of Renal Clear Cell Carcinoma and Renal Papillary Cell Carcinoma

Abstract: Kidney cancer encompasses a range of primary cancers, such as clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Our knowledge about the tumor microenvironment (TME) of kidney cancer is still limited. Therefore, we comprehensively assessed the TME of kidney cancers (including ccRCC and pRCC) using the ESTIAMTE, and CIBERSORT algorithms, and conducted distinct functional and correlation analyses with data from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), Gene Expression Omnibus (GEO), Connectivity map and CellMiner database. Next, we identified two immune-related hub genes, IGLL5 and IL2RA, which play essential roles in the TME as well as on survival in ccRCC and pRCC. Furthermore, ccRCC and pRCC samples from our medical center were collected to verify the clinical application value of these two immune-related genes. A specific enrichment analysis of immune cells related to IGLL5 and IL2RA was also conducted in two types of renal cell cancer. Based on selected genes, we predicted the drug response and uncovered novel drug candidate for RCC treatment. Considering the unfavorable outcomes of kidney cancer and emerging interest in TME-targeted treatments, our results may offer insights into immune-related molecular mechanisms and possible targets to control the kidney cancer.

A review of clinical and MR imaging features of renal lipid-poor angiomyolipomas.

Abstract: Lipid-poor angiomyolipomas (lpAMLs) constitute up to 5% of renal angiomyolipomas and are challenging to differentiate from malignant renal lesions on imaging alone. This review aims to identify clinical and MRI features which can be utilized to improve specificity and diagnostic accuracy for detecting lpAMLs in patients being considered for active surveillance rather than intervention. Young age, female sex, and small lesion size are associated with lpAMLs in studies evaluating indeterminate renal lesions. The accuracy of criteria using T2-weighted imaging, diffusion-weighted imaging, chemical shift imaging, dynamic contrast enhancement, multiparametric imaging, and radiomics are reviewed. Low T2 signal intensity is a particularly important MRI feature for lpAML. In studies with low T2 signal intensity, homogeneous early enhancement is a typical feature with an arterial-to-delay enhancement ratio > 1.5. Intratumoral hemorrhage with decrease in signal intensity on in-phase chemical shift imaging may be particularly useful for differentiating papillary renal cell carcinomas from lpAMLs in low T2 signal intensity lesions. Combining clinical and multiparametric MRI features can result in near-perfect specificity for lpAML. In select patients, clinical and MRI features can result in a high specificity and diagnostic accuracy for lpAMLs. These lesions can be considered for active surveillance rather than invasive diagnostic and therapeutic procedures such as biopsy or surgery.