J Pathol Transl Med.  2022 Nov;56(6):326-333. 10.4132/jptm.2022.10.17.

Biomarker testing of cytology specimens in personalized medicine for lung cancer patients

• Kim H
• Chung JH

• KMID: 2535852
• DOI: http://doi.org/10.4132/jptm.2022.10.17

Abstract

Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.

Keyword

Lung neoplasms; Cytology; Molecular testing; Biomarkers; Precision m

Figure

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  Fig. 1. Reperesentatvie microscopic findings according to cytologic preparations diagnosed as metastatic non-small cell carcinoma. (A) Direct smear of endobronchial ultrasound–guided fine needle aspiration samples from mediastinal lymph nodes (Papanicolaou stain). (B, C) Cytospin and liquid based preparation of pleural fluids from advanced lung cancer patients, respectively (Papanicolaou stain). (D) Cell block from (B).

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  Fig. 2. Fluorescence in situ hybridization using an LSI anaplastic lymphoma kinase (ALK) dual-color break-apart probe (A) and immunocytochemical staining using ALK D5F3 clone (B) on cytologic blocks of lung adenocarcinoma. (A) Two distinct red and green (break apart) signals with one intact fusion signal patterns (arrows) and an isolated red signal (IRS) with one intact fusion signal pattens (asterisks) were observed in > 50% of tumor cells. (B) Tumor cells exhibited strong, granular, and diffuse cytoplasmic signal, indicating aberrant ALK protein expression generated by gene fusion.

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  Fig. 3. Programmed death–ligand 1 (PD-L1) expression on a cytological cell block of pericardial fluid with advanced lung adenocarcinoma patient using the PD-L1 22C3 PharmDx assay.

Reference

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