1. Quantum Cascade Laser-Based Infrared Imaging as a Label-Free and Automated Approach to Determine Mutations in Lung Adenocarcinoma
- Author
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Jana Fassunke, Klaus Gerwert, Frederik Großerueschkamp, Reinhard Buettner, Nina Goertzen, Yon-Dschun Ko, Joachim Schmidt, Roberto Pappesch, and Thomas Brüning
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,DNA Mutational Analysis ,Adenocarcinoma of Lung ,medicine.disease_cause ,Sensitivity and Specificity ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Spectroscopy, Fourier Transform Infrared ,medicine ,Humans ,Typing ,Lung cancer ,Aged ,030304 developmental biology ,Aged, 80 and over ,Microscopy ,0303 health sciences ,Mutation ,Oncogene ,business.industry ,Middle Aged ,medicine.disease ,Molecular diagnostics ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Immunohistochemistry ,Female ,KRAS ,Lasers, Semiconductor ,business - Abstract
Therapeutic decisions in lung cancer critically depend on the determination of histologic types and oncogene mutations. Therefore, tumor samples are subjected to standard histologic and immunohistochemical analyses and examined for relevant mutations using comprehensive molecular diagnostics. In this study, an alternative diagnostic approach for automatic and label-free detection of mutations in lung adenocarcinoma tissue using quantum cascade laser-based infrared imaging is presented. For this purpose, a five-step supervised classification algorithm was developed, which was not only able to detect tissue types and tumor lesions, but also the tumor type and mutation status of adenocarcinomas. Tumor detection was verified on a data set of 214 patient samples with a specificity of 97% and a sensitivity of 95%. Furthermore, histology typing was verified on samples from 203 of the 214 patients with a specificity of 97% and a sensitivity of 94% for adenocarcinoma. The most frequently occurring mutations in adenocarcinoma (KRAS, EGFR, and TP53) were differentiated by this technique. Detection of mutations was verified in 60 patient samples from the data set with a sensitivity and specificity of 95% for each mutation. This demonstrates that quantum cascade laser infrared imaging can be used to analyze morphologic differences as well as molecular changes. Therefore, this single, one-step measurement provides comprehensive diagnostics of lung cancer histology types and most frequent mutations.
- Published
- 2021