A targeted expression panel for classification, gene fusion detection and PD-L1 measurements – Can molecular profiling replace immunohistochemistry in non-small cell lung cancer?

TY - JOUR

T1 - A targeted expression panel for classification, gene fusion detection and PD-L1 measurements – Can molecular profiling replace immunohistochemistry in non-small cell lung cancer?

AU - Simonsen, Anita Tranberg

AU - Utke, Amalie

AU - Lade-Keller, Johanne

AU - Thomsen, Lasse Westphal

AU - Steiniche, Torben

AU - Stougaard, Magnus

N1 - Publisher Copyright: © 2022 The Authors

PY - 2022/4

Y1 - 2022/4

N2 - The histological classification of non-small-cell lung cancer (NSCLC) and identification of possible therapeutic targets are important for disease management. However, as biopsies are often small, with a limited amount of tumor cells, it can be challenging to obtain enough tissue for the needed number of diagnostic immunohistochemical stains and molecular analyses. In this study, we combined a small custom designed targeted expression panel with a commercial fusion transcript assay by which we were able to perform both a histological classification (transcribing the expression of the genes encoding TTF1, Napsin A, CK5/6, and the truncated P63 isoform ΔNp63 (p40) into either adenocarcinoma or squamous cell carcinoma) and an identification of fusion genes involving ALK, RET, and ROS1. The expression panel also included the PD-L1 encoding gene, CD274, in order to evaluate the PD-L1 mRNA potential for identification of patients who will benefit from immune checkpoint inhibitor treatment. We evaluated the panel using 42 NSCLC patient samples. The molecular profiling agreed with the original immunohistochemistry (IHC)-based classification in 93% of the cases. For ten of the patients, being fusion gene positive, the fusion transcripts were detected in 100%. The molecular assessment of PD-L1 also showed agreement with the original assessment made by IHC. In conclusion, this study presents a small, targeted expression panel with the potential to perform both a molecularly based histological classification and a fusion gene identification in NSCLC patients as well as identifying PD-L1 status from a very limited amount of starting material.

AB - The histological classification of non-small-cell lung cancer (NSCLC) and identification of possible therapeutic targets are important for disease management. However, as biopsies are often small, with a limited amount of tumor cells, it can be challenging to obtain enough tissue for the needed number of diagnostic immunohistochemical stains and molecular analyses. In this study, we combined a small custom designed targeted expression panel with a commercial fusion transcript assay by which we were able to perform both a histological classification (transcribing the expression of the genes encoding TTF1, Napsin A, CK5/6, and the truncated P63 isoform ΔNp63 (p40) into either adenocarcinoma or squamous cell carcinoma) and an identification of fusion genes involving ALK, RET, and ROS1. The expression panel also included the PD-L1 encoding gene, CD274, in order to evaluate the PD-L1 mRNA potential for identification of patients who will benefit from immune checkpoint inhibitor treatment. We evaluated the panel using 42 NSCLC patient samples. The molecular profiling agreed with the original immunohistochemistry (IHC)-based classification in 93% of the cases. For ten of the patients, being fusion gene positive, the fusion transcripts were detected in 100%. The molecular assessment of PD-L1 also showed agreement with the original assessment made by IHC. In conclusion, this study presents a small, targeted expression panel with the potential to perform both a molecularly based histological classification and a fusion gene identification in NSCLC patients as well as identifying PD-L1 status from a very limited amount of starting material.

KW - Gene fusion

KW - NGS

KW - NSCLC

KW - PD-L1

KW - RNA expression

UR - http://www.scopus.com/inward/record.url?scp=85124518716&partnerID=8YFLogxK

U2 - 10.1016/j.yexmp.2022.104749

DO - 10.1016/j.yexmp.2022.104749

M3 - Journal article

C2 - 35093316

AN - SCOPUS:85124518716

SN - 0014-4800

VL - 125

JO - Experimental and Molecular Pathology

JF - Experimental and Molecular Pathology

M1 - 104749

ER -