Predictive Immunohistochemical Biomarkers for Antibody-Drug Conjugate Therapy in Pulmonary Cytology

The management of lung cancer has undergone a major transformation with the advent of precision oncology, where treatment decisions increasingly rely on tumor-specific biomarkers rather than morphology alone. In advanced-stage disease, pulmonary cytology specimens are often the only diagnostic material available. Cytological preparations are increasingly important in the workup of NSCLC. Cell blocks are among the available preparation methods that can be used for morphological evaluation and ancillary testing, including immunohistochemistry (IHC) and molecular studies. With advances in transcriptomic and proteomic profiling, several novel biomarkers have emerged beyond conventional lineage-specific markers, expanding the role of IHC in prognostication, prediction of therapeutic response and therapeutic selection. This has become particularly important in the era of antibody-drug conjugates (ADCs), which selectively target tumor-associated antigens while minimizing damage to normal tissue.

Cytology preparations, in all their forms, have become increasingly important in the diagnostic and predictive evaluation of non-small cell lung carcinoma (NSCLC). IHC remains one of the most practical and widely accessible methods for biomarker assessment, particularly in resource limited settings. Several ADC-related biomarkers, including HER2, MET, TROP2, and HER3 have recently gained therapeutic relevance, with multiple targeted agents either approved or under active clinical investigation. In addition, emerging biomarkers such as MTAP deficiency further broaden the predictive biomarker landscape and can be reliably assessed using IHC. This review summarizes the current understanding and evolving data regarding immunohistochemical biomarkers in pulmonary cytology, with special emphasis on ADC-related markers and their application in cell block preparations. The biological rationale, diagnostic utility, therapeutic implications, interpretation criteria, and limitations of these biomarkers are discussed.

Various cytological preparations from pulmonary cytology specimens can be used for diagnostic and predictive biomarker testing in lung carcinoma. IHC-based evaluation of emerging biomarkers is increasingly important for guiding personalized therapy, particularly in the context of ADCs and targeted treatment strategies. A clear understanding of the interpretation and limitations of these biomarkers is essential for pathologists involved in thoracic cytopathology and precision oncology.