scholarly journals Co-stimulatory and co-inhibitory immune markers in solid tumors with MET alterations

2021 ◽  
Vol 7 (2) ◽  
pp. FSO662
Author(s):  
Karen L Reckamp ◽  
Jasmine A McQuerry ◽  
Isa Mambetsariev ◽  
Rebecca Pharaon ◽  
Susan E Yost ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Checkpoint Inhibitors ◽  
Splice Site Mutation ◽  
Immune Markers ◽  
Site Mutation ◽  
Met Amplification ◽  
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Immune Profiling ◽  
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The implication of MET alterations in solid tumors and the immune microenvironment remains elusive. Formalin-fixed, paraffin-embedded samples of 21 patients with solid tumors harboring MET alterations were used for immunohistochemical staining. Extracted RNA was analyzed with the NanoString nCounter human PanCancer immune profiling panel (NanoString Technologies, Inc., WA, USA). Patients were diagnosed with lung (n = 10), breast (n = 5), genitourinary (n = 3) or colorectal cancer (n = 3). Eleven had a MET missense mutation, four had an exon 14 splice site mutation and six had MET amplification. CD6, CCL19, CD40LG, XCR1, MAGEA1, ATM and CCL19 genes were significantly differentially expressed in MET-altered cancers. MET alterations may have a role in various solid tumors as potential therapeutic targets and combination therapy candidates with immune checkpoint inhibitors.

scholarly journals Tumor mutation burden testing: a survey of the International Quality Network for Pathology (IQN Path)

2021 ◽  
Author(s):  
Francesca Fenizia ◽  
Nicola Wolstenholme ◽  
Jennifer A. Fairley ◽  
Etienne Rouleau ◽  
Melanie H. Cheetham ◽  
...  
Keyword(s):  
Current Practice ◽  
Checkpoint Inhibitors ◽  
Testing Methods ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Tumor Mutation Burden ◽  
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Mutation Burden ◽  
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AbstractWhile tumour mutation burden (TMB) is emerging as a possible biomarker for immune-checkpoint inhibitors (ICI), methods for testing have not been standardised as yet. In April 2019, the International Quality Network for Pathology (IQN Path) launched a survey to assess the current practice of TMB testing. Of the 127 laboratories that replied, 69 (54.3%) had already introduced TMB analysis for research purposes and/or clinical applications. Fifty laboratories (72.5%) used targeted sequencing, although a number of different panels were employed. Most laboratories tested formalin-fixed paraffin-embedded material (94.2%), while 18/69 (26%) tested also cell-free DNA. Fifty-five laboratories used both single nucleotide variants and indels for TMB calculation; 20 centers included only non-synonymous variants. In conclusion, the data from this survey indicate that multiple global laboratories were capable of rapidly introducing routine clinical TMB testing. However, the variability of testing methods raises concerns about the reproducibility of results among centers.

scholarly journals Comprehensive NGS Panel Validation for the Identification of Actionable Alterations in Adult Solid Tumors

2021 ◽  
Vol 11 (5) ◽  
pp. 360
Author(s):  
Paula Martínez-Fernández ◽  
Patricia Pose ◽  
Raquel Dolz-Gaitón ◽  
Arantxa García ◽  
Inmaculada Trigo-Sánchez ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Limit Of Detection ◽  
Copy Number Variants ◽  
Hybridization Capture ◽  
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Ffpe Tumor ◽  
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Tumor Types ◽  
Next Generation Sequencing Ngs ◽  
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The increasing identification of driver oncogenic alterations and progress of targeted therapies addresses the need of comprehensive alternatives to standard molecular methods. The translation into clinical practice of next-generation sequencing (NGS) panels is actually challenged by the compliance of high quality standards for clinical accreditation. Herein, we present the analytical and clinical feasibility study of a hybridization capture-based NGS panel (Action OncoKitDx) for the analysis of somatic mutations, copy number variants (CNVs), fusions, pharmacogenetic SNPs and Microsatellite Instability (MSI) determination in formalin-fixed paraffin-embedded (FFPE) tumor samples. A total of 64 samples were submitted to extensive analytical validation for the identification of previously known variants. An additional set of 166 tumor and patient-matched normal samples were sequenced to assess the clinical utility of the assay across different tumor types. The panel demonstrated good specificity, sensitivity, reproducibility, and repeatability for the identification of all biomarkers analyzed and the 5% limit of detection set was validated. Among the clinical cohorts, the assay revealed pathogenic genomic alterations in 97% of patient cases, and in 82.7%, at least one clinically relevant variant was detected. The validation of accuracy and robustness of this assay supports the Action OncoKitDx’s utility in adult solid tumors.

Programmed death-ligand 1 (PD-L1) expression in small cell carcinoma of bladder.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16019-e16019
Author(s):  
Angela Sanguino ◽  
Arash Samiei ◽  
Gurleen Pasricha ◽  
Lakshmi Harinath ◽  
Ralph Miller ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Tumor Cells ◽  
Small Cell Carcinoma ◽  
Mononuclear Cells ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
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Programmed Death ◽  
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e16019 Background: Small cell carcinoma of bladder (SCCB) is a rare but aggressive variant of bladder neoplasm. There is limited insight for risk prognostication and treatment guidance in this entity. Immune checkpoint inhibitors (ICI), anti-PD-1 or anti-PD-L1 antibodies, have been approved for treating urothelial carcinoma, while the evidence of their efficacy in SCCB is lacking. PD-L1 expression in tumor tissue of urothelial cancer has been postulated to correlate with response to ICI but with controversy. We have studied the expression of PD-L1 in SCCB and its association with patient survival. Methods: Nineteen cases of SCCB diagnosed between 2011 and 2017 in a single center were identified. Formalin-fixed paraffin-embedded tumor samples were stained for PD-L1 (Ventana PD-L1 SP142). Cases showing positive stain in 5% or more of tumor cells and tumor stromal mononuclear cells (TSMC) were considered positive. Results: Among 19 cases of SCCB, 4 (21%) stained positive for PD-L1. All 4 cases had strong PD-L1 staining ( > 30%) seen in the TSMC but barely in tumor cells (focal < 5% cells in 2/4 cases). Except for one patient who died from surgery, all remaining 3 patients with positive PD-L1 staining are still alive. Twelve out of 19 SCCB patients developed metastatic disease; 4 of them were treated with ICI. The only responder of the 4 patients had strong PD-L1 expression in TSMC cells. The overall survival for patients with positive PD-L1 staining was 41 months versus 14 months for those with negative staining (p = 0.09). Age, pathologic stage and treatments were similar between the two groups. Conclusions: In our study, PD-L1 expression was seen in 21% of tumor samples from patients with SCCB, mostly in TSMC, but minimal in tumor cells. The strong expression of PD-L1 in TSMC correlates with a trend of improved survival and potential response to ICI in SCCB. PD-L1 expression in TSMC, rather than tumor cells, could be used as a marker for prognosis in SCCB.

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