scholarly journals Analysis of Single Circulating Tumor Cells in Renal Cell Carcinoma Reveals Phenotypic Heterogeneity and Genomic Alterations Related to Progression

2020 ◽  
Vol 21 (4) ◽  
pp. 1475
Author(s):  
Vera Cappelletti ◽  
Elena Verzoni ◽  
Raffaele Ratta ◽  
Marta Vismara ◽  
Marco Silvestri ◽  
...  

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix™ approach for CTC-enrichment coupled with positive and negative selection with the DEPArray™ with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold ≥1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.

Author(s):  
Brusabhanu Nayak ◽  
Sridhar Panaiyadiyan ◽  
Prabhjot Singh ◽  
Subhradip Karmakar ◽  
Seema Kaushal ◽  
...  

2019 ◽  
Vol 9 ◽  
Author(s):  
Matteo Santoni ◽  
Alessia Cimadamore ◽  
Liang Cheng ◽  
Antonio Lopez-Beltran ◽  
Nicola Battelli ◽  
...  

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 506-506 ◽  
Author(s):  
Ilya Tsimafeyeu ◽  
Alexandra Naumova ◽  
Evgenia Stepanova ◽  
Alfia Khasanova ◽  
Ilya Varlamov ◽  
...  

506 Background: In our previous study we showed that fibroblast growth factor receptor 2 (FGFR2) mutations are rare across papillary types of renal cell carcinoma (pRCC). The aim of the present study is to test FGFR2 expression for association with survival outcome in the largest patient cohort to date. Methods: Formalin-fixed, paraffin-embedded specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody (Santa Cruz Biotechnology). Expression was quantified by consensus of two independent observers using a four-value intensity score (0, 1+, 2+, and 3+) and the percentage (0-100%) of the extent of reactivity. Expression was scored according to the percentage of positive cells present among all tumor cells in the section. The cytoplasmic and nuclear expression score was obtained by multiplying the intensity and reactivity extension values (range, 0-300). FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response. Results: Expression of FGFR2 was observed in 23% (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. 2 of 214 (1%) patients had nuclear FGFR2 expression. Intensity was 3+ in all cases. Expression of FGFR2 was significant lower in the normal tissue of kidney (1%, P=0.001). FGFR2 expression was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0-1), type 2 of pRCC, lower nucleolar grade (P<0.001). FGFR2-positive patients had significantly shorter OS and PFS in first-line therapy (P<0.05; Table). On multivariate analysis, FGFR2 expression, MSKCC risk group, and type of pRCC were found to be independent predictors of survival. Conclusions: In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. Clinical trial information: rosoncoweb2011. [Table: see text]


2020 ◽  
Vol 162 ◽  
pp. 112250 ◽  
Author(s):  
Jiyoon Bu ◽  
Ashita Nair ◽  
Luke J. Kubiatowicz ◽  
Michael J. Poellmann ◽  
Woo-jin Jeong ◽  
...  

2015 ◽  
Vol 26 ◽  
pp. vi62
Author(s):  
E. Verzoni ◽  
P. Grassi ◽  
V. Cappelleti ◽  
C. Maggi ◽  
R. Montone ◽  
...  

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