Multiplatform molecular analysis of biomarkers in renal cell carcinoma.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 501-501 ◽  
Author(s):  
Thai Huu Ho ◽  
Sherri Z. Millis ◽  
Nancy Doll ◽  
Zoran Gatalica ◽  
Sandeep K. Reddy ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Collecting Duct ◽  
Predictive Biomarkers ◽  
Molecular Profiling ◽  
Aberrant Expression ◽  
Duct Carcinoma ◽  
The Impact

501 Background: Predictive biomarkers of response to targeted therapy are lacking in renal cell carcinoma (RCC). We evaluated a cohort of RCC patients referred for molecular profiling to identify potentially actionable recurrent molecular aberrations. Methods: 166 consecutive renal cases referred to Caris Life Sciences over 2 yrs were evaluated with central pathology review. Cases were subtyped into clear cell (ccRCC), n=100, papillary (PRCC), n=20, sarcomatoid, n=10, translocation, n=6, medullary, n=4 or unclassified, n=26. 63% of cases were metastatic. Testing included a combination of sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]), and/or gene amplification (CISH or FISH). Results: ccRCC had a 52% loss of PTEN, while PRCC had a 21% loss (p value=0.02). 100% of ccRCC with sarcomatoid features (4) showed aberrant expression of PD-L1 and were infiltrated with PD-1+ tumor infiltrating lymphocytes; 100% of 10 non-ccRCC sarcomatoids also had aberrant expression of PD-L1. Loss of PBRM1 expression was observed in 60% of ccRCC. Loss of histone 3 lysine 36 trimethylation (H3K36me3), which is associated with SETD2 mutations, was observed in 30% of ccRCC. TOP2A was overexpressed in ccRCC at 30% and in non-ccRCC at 50%. 100% of ccRCC and PRCC overexpressed EGFR; a single unclassified renal cell carcinoma did not overexpress EGFR. 50% of cases had cMET overexpression, amplification, or mutation. HER2 was not amplified or overexpressed in any RCC; a single rare HER2 mutation (R816H) was found in a collecting duct carcinoma. VHL mutations were identified in 50% of ccRCC tumors. We observed lower rates of TP53 (14%), ATM (6%), and PIK3CA(4% ccRCC, 7% PRCC) mutations compared to other cancers. Conclusions: Multiplatform molecular profiling of renal cell carcinoma identifies potential predictive biomarkers in ccRCC. The documented activity of everolimus in ccRCC (RECORD-1 trial) may be attributable to PIK3CA pathway alterations. RCC with sarcomatoid features may respond to PD1/PD-L1 targeted immunotherapies. The impact of molecular profiling in ccRCC to predict responses to currently available targeted therapy has important implications for trial design and patient selection.

scholarly journals Comprehensive Immunoprofiles of Renal Cell Carcinoma Subtypes

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 602 ◽  
Author(s):  
Moonsik Kim ◽  
Jin Woo Joo ◽  
Seok Joo Lee ◽  
Yoon Ah Cho ◽  
Cheol Keun Park ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Collecting Duct ◽  
Cathepsin K ◽  
Renal Tumors ◽  
Duct Carcinoma ◽  
Epithelial Tumors ◽  
Papillary Type

In recent years, renal epithelial tumors have been among the fastest reclassifying tumors, requiring updates to the tumor classification system. Nonetheless, immunohistochemistry (IHC) remains the most widely used tool for renal epithelial tumors. In this proposal, we aimed to create the most efficient IHC panel for categorizing the diverse subtypes of renal tumors, and to find out more specific immunohistochemical results in each subtype or each antibody. A total of 214 renal tumors were analyzed using 10 possible IHC markers to differentiate subtypes, including three major renal cell carcinoma (RCC) subtypes, clear-cell type (50 cases), papillary type (50 cases), and chromophobe type (20 cases), and minor subtypes (MiT RCC, 13 cases; collecting duct carcinoma, 5 cases; and oncocytoma, 10 cases). A triple immunomarker (cytokeratin 7 (CK7)-carbonic anhydrase IX (CAIX)- alpha-methylacyl-CoA racemase (AMACR)) panel is useful in particular high-grade clear-cell tumors. If IHC remains ambiguous, the use of an adjunctive panel can be suggested, including CD10, epithelial membrane antigen, cathepsin K, c-kit, hepatocyte nuclear factor 1-β, and E-cadherin. For an efficient immunohistochemical strategy for subtyping of RCC, we conclude that the CK7-CAIX-AMACR panel is the best primary choice for screening subtyping.

Histopathology in surgically treated renal cell carcinoma: Is there a survival difference when stratified by stage?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5089-5089
Author(s):  
K. A. Keegan ◽  
N. J. Hellenthal ◽  
K. Chamie ◽  
T. M. Koppie
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Collecting Duct ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Cancer Specific Survival ◽  
Stage Disease ◽  
The Impact

5089 Background: The impact of renal cell carcinoma histopathology (RCC) on survival has been conflicting and limited to retrospective institutional studies. Therefore, we sought to determine the role of RCC histopathology on stage-specific survival rates in a population-based cohort. Methods: We utilized the National Cancer Institute's Surveillance, Epidemiology, and End Results database and identified 21,258 patients who underwent partial or radical nephrectomy for RCC between 1996 and 2004. Patients were stratified based on histopathologic diagnosis (clear cell, papillary, chromophobe, sarcomatoid, and collecting duct) and pathologic stage. We performed Cox-proportional hazard modeling and Kaplan-Meier survival analyses to determine overall- and cancer-specific survival. Results: Using univariate analysis, histopathology significantly impacted overall- and cancer-specific survival (p< 0.001). Specifically, patients with papillary and chromophobe variants had lower stage disease at the time of surgery and had improved survival compared to clear cell subtypes, (HR: 0.50; 95% CI, 0.42–0.60 and HR: 0.31; 95% CI, 0.22–0.44, respectively). When controlled for stage, improved outcomes for chromophobe and papillary histologies persisted, although it did not achieve statistical significance at all stages. On the other hand, patients with sarcomatoid disease were more likely to present with high stage disease and invariably had worse survival compared to clear cell carcinoma (HR: 8.74; 95%, CI 7.70–9.91). When controlled for stage, this difference achieved statistical significance across all stages (p< 0.001). Conclusions: Histopathologic subtype in patients with RCC does predict overall- and cancer-specific survival. Patients with sarcomatoid RCC, even those presenting with low-stage disease, have poor survival. These findings may give further value to recent data suggesting the increased utility of percutaneous renal biopsy and its potential impact on management. [Table: see text] No significant financial relationships to disclose.

scholarly journals The Differential Diagnosis of Medullary-Based Renal Masses

2021 ◽  
Author(s):  
Nicholas Baniak ◽  
Harrison Tsai ◽  
Michelle S. Hirsch
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Collecting Duct ◽  
Fumarate Hydratase ◽  
Growth Patterns ◽  
Renal Tumors ◽  
Renal Masses ◽  
Duct Carcinoma

Context.— Renal malignancies can be divided into cortical- and medullary-based tumors, the latter of which classically infiltrate the renal parenchyma by extending between nonneoplastic structures. Although high-grade cortical tumors can rarely exhibit the same growth pattern, the infiltrative morphology should elicit a differential diagnosis to be considered in each case. However, these diagnoses can be challenging to distinguish, especially on small renal biopsy samples. Objective.— To provide an overview of the clinical, gross, and microscopic findings; genetic and molecular alterations; and immunohistochemical evaluation of medullary-based renal tumors and other tumor types with overlapping morphologies and growth patterns. Data Sources.— Literature review and personal observations were used to compile the information in this review. Conclusions.— Collecting duct carcinoma is a prototypical medullary-based tumor, and although diagnostic criteria exist, it remains a diagnosis of exclusion, especially with ancillary techniques aiding the recognition of established as well as more recently described neoplasms. Other medullary-based malignancies included in the differential diagnosis include renal medullary carcinoma/renal cell carcinoma unclassified with medullary phenotype, fumarate hydratase–deficient renal cell carcinoma, and upper tract urothelial carcinoma. Moreover, other rare entities should be excluded, including metastatic carcinoma, lymphoma, and melanoma. In addition to potential prognostic differences, accurate diagnoses can have important surgical and clinical management implications.

scholarly journals Impact of neutrophil-to-lymphocyte ratio on effects of targeted therapy for metastatic renal cell carcinoma patients with extrapulmonary metastasis

2017 ◽  
Vol 11 (5) ◽  
pp. 207 ◽  
Author(s):  
Jun Teishima ◽  
Shinya Ohara ◽  
Kousuke Sadahide ◽  
Shinsuke Fujii ◽  
Hiroyuki Kitano ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Predictive Factor ◽  
Renal Cell ◽  
Neutrophil To Lymphocyte Ratio ◽  
Independent Predictive Factor ◽  
Lymphocyte Ratio ◽  
The Impact

Introduction: The aim of our present study was to investigate the impact of the pretreatment neutrophil-to-lymphocyte ratio (NLR) on the antitumour effects of targeted agents in patients with metastatic renal cell carcinoma (mRCC).Methods: The NLRs in 283 cases of molecular targeted therapy for mRCC were measured before starting the prescription of the molecular targeted agent. The significance of pretreatment NLR on the site of metastatic organs and on progression-free survival (PFS)in each case was analyzed.Results: Metastases other than lung, which is defined as “extrapulmonary metastasis,” were observed in 190 cases (67.1%). The median of pretreated NLR was 2.39 (0.49‒68.7). In 97 of the 283 cases,pretreated NLR was 3.0 or higher. These cases were categorized as the high NLR group and the rest as the low NLR group. When the cases with extrapulmonary metastasis were investigated and classifiedbased on their pretreated NLR, 50% PFS in the high NLR and low NLR groups was 6.7 months and 12 months (p=0.0001), respectively. Multivariate analysis revealed that high NLR (>3.0) was an independent predictive factor for PFS in the cases with extrapulmonary metastasis (hazard ratio 2.762; p<0.0001), while there was no significant difference between PFS in the high and low NLR groups in cases with no extrapulmonary metastasis (p=0.3457).Conclusions: Our data indicate that the predictive significance of the NLR in mRCC cases involving targeted therapy depends on the metastatic organs. NLR is an independent predictive factor of PFS in cases of mRCC with extrapulmonary metastasis treated with targeted therapy.

scholarly journals CT and MRI findings of cystic renal cell carcinoma: comparison with cystic collecting duct carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingqiang Zhu ◽  
Jun Ling ◽  
Jing Ye ◽  
Wenrong Zhu ◽  
Jingtao Wu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Collecting Duct ◽  
Imaging Features ◽  
Mri Findings ◽  
Duct Carcinoma ◽  
Collecting Duct Carcinoma ◽  
Cystic Renal Cell Carcinoma ◽  
T2 Weighted Images

Abstract Background Cystic renal cell carcinoma (CRCC) and cystic collecting duct carcinoma (CCDC) share similar oncogeni and some imaging findings. The aim of this study was to characterize the clinical and CT imagings features of CRCC and CCDC. Methods Thirty-three patients with CRCC and thirteen patients with CCDC with pathologically proven were retrospectively studied. Tumor characteristics were assessed. Results On CT imaging, 33 patients(100 %) with CRCC and 13 patients(100 %) with CCDC, tumors calcifications (8 vs. 9, P < 0.0001), had a clear boundary (capsule sign, 30 vs. 2, P < 0.0001), infiltrative appearance (1 vs. 13, P < 0.0001), exogenous appearance (29 vs. 3, P < 0.0001), invaded the renal pelvis or ureter (1 vs. 10, P < 0.0001), hemorrhage (1 vs. 10, P < 0.0001), had retroperitoneal lymph node or distant metastasis (2 vs. 10, P < 0.0001), thickened enhancing internal septations (31 vs. 2, P < 0.0001), and mural soft-tissue nodules (21 vs. 1, P < 0.0001). On MR imaging,13 patients(39 %) with CRCC and 4 patients(31 %) with CCDC, all CRCCs appeared hypointense on T1-weighted images and hyperintense on T2-weighted images, however, all CCDCs appeared hypointense on T1-weighted images and hypointense on T2-weighted images(P < 0.0001). 33 patients with CRCC, they were all alive from3 years to 10 years follow-up, however, 13 patients with CCDC, of which 11 patients were able to be followed up, and 9 patients expired within 5 years of the initial diagnosis and the others are currently still alive. Conclusions Distinguishing features of CRCC and CCDC included calcifications, capsule signs, infiltrative appearance, metastasis, internal septations, mural nodules and signal on CT or MR images. These imaging features may help in differentiating the two renal tumor types.

Renal Cell Carcinoma, Chromophobe Type, With Collecting Duct Carcinoma and Sarcomatoid Components

2003 ◽  
Vol 127 (1) ◽  
pp. e38-e40 ◽  
Author(s):  
Yun Gong ◽  
Xiaoping Sun ◽  
G. Kenneth Haines ◽  
Michael R. Pins
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Collecting Duct ◽  
Inflammatory Cells ◽  
Chromophobe Renal Cell Carcinoma ◽  
Duct Carcinoma ◽  
Collecting Duct Carcinoma ◽  
Collecting Duct Epithelium ◽  
Immunohistochemical Studies

Abstract We report a case of a 72-year-old man with a chromophobe renal cell carcinoma that had both sarcomatoid and collecting duct carcinoma components. The 7-cm tumor occupied the entire lower pole of the kidney and infiltrated the renal parenchyma and the pelvic-calyceal system. Histologically, it had an area of classic chromophobe renal cell carcinoma that merged into a sarcomatoid component. Closely intermixed with the sarcomatoid component was a collecting duct carcinoma component characterized by highly pleomorphic, epithelioid cells arranged in cords, nests, and tubulomicrocystic structures. The cords, nests, and tubules were associated with a florid desmoplastic stromal response and numerous inflammatory cells. In addition, dysplastic changes were noted in adjacent nonneoplastic collecting duct epithelium. Immunohistochemical studies confirmed the presence of 3 distinct components in this patient's tumor. To the best of our knowledge, this is the first reported case of a chromophobe renal cell carcinoma with sarcomatoid and collecting duct carcinoma components.

Sign in / Sign up

Export Citation Format

Share Document