Advertisement

Topics

Assessment of PD-L1 mRNA and protein expression in non-small cell lung cancer, head and neck squamous cell carcinoma and urothelial carcinoma tissue specimens using RNAScope and immunohistochemistry.

08:00 EDT 15th April 2019 | BioPortfolio

Summary of "Assessment of PD-L1 mRNA and protein expression in non-small cell lung cancer, head and neck squamous cell carcinoma and urothelial carcinoma tissue specimens using RNAScope and immunohistochemistry."

Four immunohistochemistry (IHC) diagnostic assays have been approved for tumour PD-L1 protein assessment in the clinic. However, mRNA detection by in situ hybridisation (ISH) could be utilised as an alternative to protein detection. Detecting spatial changes in gene expression provides vital prognostic and diagnostic information, particularly in immune oncology where the phenotype, cellular infiltration and immune activity status may be associated with patient survival. Translation of mRNA expression to a clinically relevant cut off or threshold is challenging due to variability between assays and the detection of different analytes. These studies aim to confirm the suitability of formalin fixed paraffin embedded (FFPE) tissue sections for use with RNA ISH. A comparison of mRNA expression and protein expression may inform the suitability of mRNA as a patient selection biomarker in a similar manner to IHC and provide evidence of a suitable scoring algorithm. Ninety patient samples, thirty for each indication of non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC) and urothelial carcinoma (UC), previously assessed using the VENTANA PD-L1 (SP263) Assay were chosen to represent a wide dynamic range of percentage tumour cell staining (TCIHC). Expression of mRNA was assessed by ISH using the RNAScope 2.5 assay and probe CD274/PD-L1 (Advanced Cell Diagnostics) including kit provided positive and negative control probes. Brightfield whole slide images of tissues were captured. The percentage of tumour cells with PD-L1 mRNA expression (%TCmRNA) and mean punctate dots/tumour cell were determined using image analysis. Differences in RNA expression between the IHC derived TCIHC≥25% and <25% groups were assessed using t-tests. For each indication, a receiver-operating characteristic (ROC) analysis identified thresholds for patient classification using %TCmRNA and dots/tumour cell, with reference to TCIHC≥25%. Eighty-six samples were successfully tested; 3 failed due to insufficient control probe staining, 1 due to lack of tumour. Percent TCmRNA staining using RNAScope demonstrated statistical significance (at α = 0.05) in the PD-L1 high (TCIHC ≥25%) vs the PD-L1 low (TCIHC <25%) groups for NSCLC, HNSCC, and UC. The number of punctate dots/tumour cell was significantly higher in the PD-L1 high vs the PD-L1 low groups for NSCLC and HNSCC but not UC. For %TCmRNA; ROC analysis identified thresholds of: NSCLC 18.0%, HNSCC 31.8%, UC 25.8%. For dots/tumour cell, thresholds were: NSCLC 0.26, HNSCC 0.53, UC 0.45. Routine tissue fixation and processing is suitable for RNA detection using RNAScope. PD-L1 mRNA extent and level is associated with PD-L1 status determined by IHC. Threshold optimisation for %TCmRNA and mean dots/tumour cell results in high specificity to IHC PD-L1 classification, but only moderate sensitivity.

Affiliation

Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0215393

Links

DeepDyve research library

PubMed Articles [51457 Associated PubMed Articles listed on BioPortfolio]

p38 MAP kinases: plausible diagnostic and prognostic serum protein marker of non small cell lung cancer.

p38 MAPK signaling molecules plays a dual role in cancer, both progression and suppression. Elevated expression of p38α was reported in lung cancer tissue in rat model. Our objective was to explore t...

Mechanism of decorin protein inhibiting invasion and metastasis of non-small cell lung cancer.

To detect the protein level of Decorin in non-small cell lung cancer (NSCLC) patients, and to study the mechanism of Decorin inhibiting invasion and metastasis of non-small cell lung cancer from the p...

The Correlation of Visfatin and Its Gene Polymorphism with Non-Small Cell Lung Cancer.

To investigate the protein expression of visfatin and its gene polymorphism in non-small cell lung cancer (NSCLC) patients.

CCDC85B promotes non-small cell lung cancer cell proliferation and invasion.

Coiled-coil domain containing 85 B (CCDC85B) is involved in diverse biological processes; however, its expression patterns and functions in human cancers are yet unknown. The present study demonstrate...

Overexpression of Alteration/Deficiency in Activation 3 correlates with poor prognosis in non-small cell lung cancer.

Alteration/Deficiency in Activation 3 (ADA3), the human homologue of yeast ADA3, is involved in a variety of cell biological processes and plays an important role in tumorigenesis. Here, western blott...

Clinical Trials [27414 Associated Clinical Trials listed on BioPortfolio]

Saliva mRNA Expression Profiling for Early Stage Non-Small Cell Lung Cancer Screening

This is a pilot study to test the feasibility of using gene expression from saliva to identify patients with early-stage non-small cell lung cancer (NSCLC). The primary objective of this ...

Retrospective Study Evaluating IGF1R And p95HER2 as Prognostic Factors in Non Small Cell Lung Cancer (NSCLC)

Aim of the study is to evaluated the role of IGF1R and p95HER2 on prognosis in radically resected non small cell lung cancer patients The primary objective is to correlate the expression ...

A Study to Assess Programmed Death Ligand-1 (PD-L1) Expression in Cytological Versus Histological Lung Cancer Specimens

The primary purpose of this non-interventional, multinational study is to assess the feasibility of assessing PD-L1 protein expression on cytological samples as a surrogate for histologica...

Construction and Use of Lung Tumor Microarray for the Analysis of Gene Expression in Lung Cancer

The proposed research intends to construct a set of tissue microarrays containing different types of normal and lung cancer tissues for the study of genes associated with lung cancer. Thus...

Clinical Research for the Consistency Analysis of PD-L1 in Cancer Tissue and Plasma Exosome

The detection of tissue PD-L1 immunohistochemistry in Non-small cell lung cancer (NSCLC) has an important role in guiding for the treatment of immune detection point. At the same time,tiss...

Medical and Biotech [MESH] Definitions

Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.

A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).

A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.

A cell adhesion molecule that contains extracellular immunoglobulin V and C2 domains. It mediates homophilic and heterophilic cell-cell adhesion independently of calcium, and acts as a tumor suppressor in NON-SMALL-CELL LUNG CANCER (NSCLC) cells. Its interaction with NATURAL KILLER CELLS is important for their cytotoxicity and its expression by MAST CELLS plays a role in their interaction with neurons; it may also function in synapse assembly, nerve growth and differentiation.

A quinazoline derivative and ANTINEOPLASTIC AGENT that functions as a PROTEIN KINASE INHIBITOR for EGFR associated tyrosine kinase. It is used in the treatment of NON-SMALL CELL LUNG CANCER.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Gilotrif (afatinib)
GILOTRIF (afatinib) is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L8...

Skin cancers
There are three main types of skin cancer: basal cell carcinoma, squamous cell carcinoma and malignant melanoma. Basal cell carcinoma Basal cell carcinoma, or BCC, is a cancer of the basal cells at the bottom of the epidermis. It’s very common ...


Searches Linking to this Article