Enhancing tumour content and tumour cell count using microdissection contributes to higher detection rate of genetic mutations by next-generation sequencers

Abstract

Background: Next-generation sequencing (NGS) analysis is becoming indispensable for the treatment of advanced lung cancer. NGS analysis requires a large number of cancer cell-containing tissues; however, it is often difficult for small biopsies to obtain the required quantities. In microdissection, only the tumour parts of a tissue specimen are obtained, which thereby increases the tumour content and tumour cell count of the tissue specimen. In this study, we investigated the extent to which the detection rate of genetic mutations changes by increasing the tumour content using microdissection. Patients and methods: This is a retrospective study. In the genetic panel test using the Oncomine Dx Target Test (ODxTT), participants were divided into two groups: before (group A; April 2021–March 2022) and after (group B; April 2022–December 2022) the introduction of microdissection. The submission criteria for ODxTT were tumour content and tumour cell count >30 % and >2000 in group A, and >40 % and >5000 in group B, respectively. We compared the rate of genetic mutations detected using ODxTT between the two groups. Results: This study included 214 consecutive ODxTT cases between April 2021 and December 2022. In group A (n = 112), 65 cases were adenocarcinoma, 84 involved lung tissue, and 64 underwent bronchoscopic sampling, whereas in group B (n = 102), 55 cases were adenocarcinoma, 91 cases involved lung tissue, and 79 cases underwent bronchoscopic sampling. Furthermore, genetic mutations were detected in 39 of 112 cases (35 %) in group A and 59 of 102 cases (58 %) in group B, which was statistically higher in group B (P = 0.0006). Genetic mutations were detected in 45 of 55 adenocarcinoma cases in group B. The genetic mutations detected in epidermal growth factor rescepor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and mesenchymal epithelial transition (MET) were higher in group B. Conclusion: Increasing the number of tumour cells and tumour content can enhance the detection rate of genetic mutations using ODxTT.

Keywords

• Oncomine Dx target test
• Microdissection
• Next-generation sequencing
• Tumour content
• Genetic mutation