scholarly journals Hyperpolarized 13C-Pyruvate Metabolism as a Surrogate for Tumor Grade and Poor Outcome in Renal Cell Carcinoma—A Proof of Principle Study

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 335
Author(s):  
Stephan Ursprung ◽  
Ramona Woitek ◽  
Mary A. McLean ◽  
Andrew N. Priest ◽  
Mireia Crispin-Ortuzar ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Regional Analysis ◽  
Disease Free Survival ◽  
Tumor Grade ◽  
Renal Tumors ◽  
Metabolic Imaging ◽  
Patient Specific ◽  
Cell Renal Cell Carcinoma

Differentiating aggressive clear cell renal cell carcinoma (ccRCC) from indolent lesions is challenging using conventional imaging. This work prospectively compared the metabolic imaging phenotype of renal tumors using carbon-13 MRI following injection of hyperpolarized [1-13C]pyruvate (HP-13C-MRI) and validated these findings with histopathology. Nine patients with treatment-naïve renal tumors (6 ccRCCs, 1 liposarcoma, 1 pheochromocytoma, 1 oncocytoma) underwent pre-operative HP-13C-MRI and conventional proton (1H) MRI. Multi-regional tissue samples were collected using patient-specific 3D-printed tumor molds for spatial registration between imaging and molecular analysis. The apparent exchange rate constant (kPL) between 13C-pyruvate and 13C-lactate was calculated. Immunohistochemistry for the pyruvate transporter (MCT1) from 44 multi-regional samples, as well as associations between MCT1 expression and outcome in the TCGA-KIRC dataset, were investigated. Increasing kPL in ccRCC was correlated with increasing overall tumor grade (ρ = 0.92, p = 0.009) and MCT1 expression (r = 0.89, p = 0.016), with similar results acquired from the multi-regional analysis. Conventional 1H-MRI parameters did not discriminate tumor grades. The correlation between MCT1 and ccRCC grade was confirmed within a TCGA dataset (p < 0.001), where MCT1 expression was a predictor of overall and disease-free survival. In conclusion, metabolic imaging using HP-13C-MRI differentiates tumor aggressiveness in ccRCC and correlates with the expression of MCT1, a predictor of survival. HP-13C-MRI may non-invasively characterize metabolic phenotypes within renal cancer.

scholarly journals Bioinformatics analysis of C3 and CXCR4 demonstrates their potential as prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jing Quan ◽  
Yuchen Bai ◽  
Yunbei Yang ◽  
Er Lei Han ◽  
Hong Bai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Therapeutic Targets ◽  
Disease Free Survival ◽  
Prognostic Biomarkers ◽  
Hub Genes ◽  
Cell Renal Cell Carcinoma ◽  
Upregulated Genes

Abstract Background The molecular prognostic biomarkers of clear cell renal cell carcinoma (ccRCC) are still unknown. We aimed at researching the candidate biomarkers and potential therapeutic targets of ccRCC. Methods Three ccRCC expression microarray datasets (include GSE14762, GSE66270 and GSE53757) were downloaded from the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) between ccRCC and normal tissues were explored. The potential functions of identified DEGs were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). And then the protein - protein interaction network (PPI) was established to screen the hub genes. After that, the expressions of hub genes were identified by the oncomine database. The hub genes’ prognostic values of patients with ccRCC were analyzed by GEPIA database. Results A total of 137 DEGs were identified by utilizing the limma package and RRA method, including 63 upregulated genes and 74 downregulated genes. It is found that 137 DEGs were mainly enriched in 82 functional terms and 24 pathways in accordance with the research results. Thirteen highest-scoring genes were screened as hub genes (include 10 upregulated genes and 3 downregulated candidate genes) by utilizing the PPI network and module analysis. Through integrating the oncoming database and GEPIA database, the author found that C3 and CXCR4 are not only overexpressed in ccRCC, but also associated with the prognosis of ccRCC. Further results could reveal that patients with high C3 expression had a poor overall survival (OS), while patients with high CTSS and TLR3 expressions had a good OS; patients with high C3 and CXCR4 expressions had a poor disease-free survival (DFS), while ccRCC patients with high TLR3 expression had a good DFS. Conclusion These findings suggested that C3 and CXCR4 were the candidate biomarkers and potential therapeutic targets of ccRCC patients.

scholarly journals Sequential immune-targeted surgical therapy resulted in disease-free survival in a case with advanced renal cell carcinoma

BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kenichi Nishimura ◽  
Noriyoshi Miura ◽  
Naoya Sugihara ◽  
Keisuke Funaki ◽  
Kanae Koyama ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Thrombus ◽  
Disease Free Survival ◽  
Sequential Therapy ◽  
Residual Tumor ◽  
Advanced Renal Cell Carcinoma ◽  
Cell Renal Cell Carcinoma ◽  
Disease Free

Abstract Background Currently, immunotherapy is indicated for patients with metastatic RCC or unresectable RCC, but there is no indication for immunotherapy in the neoadjuvant setting. We report a case in which the combined use of nivolumab and ipilimumab and sequential TKI therapy enabled surgical treatment. Case presentation A 71-year-old female was diagnosed with a metastatic clear-cell renal cell carcinoma with a level IV tumor thrombus. She was started on nivolumab-ipilimumab therapy, and was switched to pazopanib monotherapy because the tumor thrombus progressed within the right atrium. The tumor shrank to resectable status with sequential therapy. She then underwent right nephrectomy and thrombectomy. Pathological analysis showed 10–20% residual tumor in the primary tumor, but no viable cells in tumor thrombus. She remains clinically disease-free 1 year after surgery. Conclusion This case suggests the utility of sequential immune-targeted therapy as neoadjuvant therapy in advanced renal cell carcinoma.

scholarly journals Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

2013 ◽  
Vol 137 (4) ◽  
pp. 467-480 ◽  
Author(s):  
Rajen Goyal ◽  
Elizabeth Gersbach ◽  
Ximing J. Yang ◽  
Stephen M. Rohan
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumor ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Immunohistochemical Stains

Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. Data Sources.—Published literature and personal experience. Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.

Expression of theForkheadTranscription Factor FOXP1 is Associated with Tumor Grade and Ki67 Expression in Clear Cell Renal Cell Carcinoma

2011 ◽  
Vol 29 (2) ◽  
pp. 123-129 ◽  
Author(s):  
Marieta I. Toma ◽  
Thomas Weber ◽  
Matthias Meinhardt ◽  
Stefan Zastrow ◽  
Marc-Oliver Grimm ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Grade ◽  
Cell Renal Cell Carcinoma ◽  
Ki67 Expression

scholarly journals Differentiation of Clear Cell Renal Cell Carcinoma from other Renal Cell Carcinoma Subtypes and Benign Oncocytoma Using Quantitative MDCT Enhancement Parameters

Medicina ◽  
2020 ◽  
Vol 56 (11) ◽  
pp. 569
Author(s):  
Claudia-Gabriela Moldovanu ◽  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Attila Tamas-Szora ◽  
Mihai Suciu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
3D Analysis ◽  
Imaging Features ◽  
Enhancement Ratio ◽  
Cell Renal Cell Carcinoma ◽  
Renal Masses

Background and objectives: The use of non-invasive techniques to predict the histological type of renal masses can avoid a renal mass biopsy, thus being of great clinical interest. The aim of our study was to assess if quantitative multiphasic multidetector computed tomography (MDCT) enhancement patterns of renal masses (malignant and benign) may be useful to enable lesion differentiation by their enhancement characteristics. Materials and Methods: A total of 154 renal tumors were retrospectively analyzed with a four-phase MDCT protocol. We studied attenuation values using the values within the most avidly enhancing portion of the tumor (2D analysis) and within the whole tumor volume (3D analysis). A region of interest (ROI) was also placed in the adjacent uninvolved renal cortex to calculate the relative tumor enhancement ratio. Results: Significant differences were noted in enhancement and de-enhancement (diminution of attenuation measurements between the postcontrast phases) values by histology. The highest areas under the receiver operating characteristic curves (AUCs) of 0.976 (95% CI: 0.924–0.995) and 0.827 (95% CI: 0.752–0.887), respectively, were demonstrated between clear cell renal cell carcinoma (ccRCC) and papillary RCC (pRCC)/oncocytoma. The 3D analysis allowed the differentiation of ccRCC from chromophobe RCC (chrRCC) with a AUC of 0.643 (95% CI: 0.555–0.724). Wash-out values proved useful only for discrimination between ccRCC and oncocytoma (43.34 vs 64.10, p < 0.001). However, the relative tumor enhancement ratio (corticomedullary (CM) and nephrographic phases) proved useful for discrimination between ccRCC, pRCC, and chrRCC, with the values from the CM phase having higher AUCs of 0.973 (95% CI: 0.929–0.993) and 0.799 (95% CI: 0.721–0.864), respectively. Conclusions: Our observations point out that imaging features may contribute to providing prognostic information helpful in the management strategy of renal masses.

Decreased prolyl hydroxylase 3 mRNA expression in oncocytomas compared with clear cell renal cell carcinoma

2020 ◽  
Vol 35 (4) ◽  
pp. 80-86
Author(s):  
Spyridon Kampantais ◽  
Ilias Kounatidis ◽  
Vasiliki Kotoula ◽  
Ioannis Vakalopoulos ◽  
Konstantinos Gkagkalidis ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Prolyl Hydroxylase ◽  
Renal Tumors ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels ◽  
Fresh Frozen

Introduction: Hypoxia inducible factors (HIF) and prolyl hydroxylase domain (PHD) enzymes play a central role in tumor progression in clear cell renal cell carcinoma (ccRCC). However, there are currently no data regarding the behavior of this pathway (HIF/PHD) in a large number of benign renal tumors, the oncocytomas. The aim of the present study was to compare the expression levels of these factors between ccRCC and oncocytoma tumors. Material and methods: A total of 56 fresh frozen specimens from patients with ccRCC and 14 oncocytoma specimens were analyzed via reverse transcription-quantitative polymerase chain reaction in order to assess the expression levels of HIF-1α, HIF-2α, PHD1, PHD2, and PHD3. The analysis involved both fresh frozen tumor samples as well as adjacent normal kidney tissues. Results: In ccRCC, HIF-1α and HIF-2α levels were upregulated in 65.5% and 71.4% of cases, respectively. PHD3 was downregulated only in 15.4% of the ccRCC cases, in contrast with oncocytoma cases, which exhibited low expression levels in the majority. The upregulation of PHD3 messenger RNA (mRNA) levels in ccRCC when compared with oncocytoma was statistically significant ( P<0.001). No other comparisons (HIF-1α, HIF-2α, PHD1, and PHD2) were significantly different. HIF-2α and PHD3 mRNA expression levels were negatively correlated with Fuhrman Grade ( P=0.029 and P=0.026, respectively) in ccRCC. Conclusion: To the best of our knowledge, this is the first time that the HIF/PHD pathway was compared between ccRCC and a common benign tumor, identifying the upregulation of PHD3 as the possible underlying factor guiding the difference in the behavior of ccRCC.

scholarly journals IKBKB expression in clear cell renal cell carcinoma is associated with tumor grade and patient outcomes

2018 ◽  
Author(s):  
Bartlomiej Krazinski ◽  
Anna Kowalczyk ◽  
Agnieszka Sliwinska‑Jewsiewicka ◽  
Jedrzej Grzegrzolka ◽  
Janusz Godlewski ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Patient Outcomes ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Grade ◽  
Cell Renal Cell Carcinoma

scholarly journals The two glycolytic markers GLUT1 and MCT1 correlate with tumor grade and survival in clear-cell renal cell carcinoma

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0193477 ◽  
Author(s):  
Damien Ambrosetti ◽  
Maeva Dufies ◽  
Bérengère Dadone ◽  
Matthieu Durand ◽  
Delphine Borchiellini ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Tumor Grade ◽  
Cell Renal Cell Carcinoma

scholarly journals Unilateral synchronous papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma: a case report with KRAS and PIK3CA mutations

2020 ◽  
Author(s):  
Hyun Jung Lee ◽  
Dong Hoon Shin ◽  
Joon Young Park ◽  
So Young Kim ◽  
Chung Su Hwang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Gene Mutation ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Tumors ◽  
Renal Neoplasm ◽  
Reverse Polarity ◽  
Cell Renal Cell Carcinoma ◽  
Exon 2

Abstract Background: The presence of histologically different neoplasms in the same organ is rare in pathologic practice. We report the first case of synchronous clear cell renal cell carcinoma (clear cell RCC) and papillary renal neoplasm with reverse polarity (PRNRP) with comprehensive immunohistochemical and molecular characterization using next-generation sequencing (NGS). Case presentation: A 61-year-old man was incidentally found to have a left renal mass on imaging studies performed for workup of left back pain and urine color change for one week. A laparoscopic left radical nephrectomy was performed. Gross examination showed lobulated masses measuring 5.6 × 4.0 × 3.3 cm in the upper to mid pole and 1.1 × 1.0 × 1.0 cm in the lower pole. Microscopic findings revealed these to be two different separate masses of clear cell renal cell carcinoma and papillary renal neoplasm with reverse polarity. NGS analyses revealed KRAS gene mutation (c.35G>T/p.G12V in exon 2) in the papillary renal neoplasm with reverse polarity, with PIK3CA gene mutation restricted to the clear cell renal cell carcinoma (c.1624G>A/p.E542K in exon 10).Conclusions: We report here an extraordinarily rare case of synchronous renal tumors of papillary renal neoplasm with reverse polarity and clear cell renal cell carcinoma. We identified simultaneous KRAS and PIK3CA mutations in two different renal masses in the same kidney for the first time. New pathologic assessment with comparative molecular analysis of mutational profiles may be helpful for tumor studies.

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