Current concepts on the molecular pathology of non-small cell lung carcinoma

Abstract

Recent advances in the understanding of the complex biology of non-small cell lung carcinoma (NSCLC), particularly activation of oncogenes by mutation, translocation and amplification, have provided new treatment targets for this disease, and allowed the identification of subsets of NSCLC tumors, mostly with adenocarcinoma histology, having unique molecular profiles that can predict response to targeted therapy. The identification of specific genetic and molecular targetable abnormalities using tumor tissue and cytology specimens followed by the administration of a specific inhibitor to the target, are the basis of personalized lung cancer treatment. In this new paradigm, the role of a precise pathology diagnosis of lung cancer and the proper handling of tissue and cytology samples for molecular testing is becoming increasingly important. These changes have posed multiple new challenges for pathologists to adequately integrate routine histopathology analysis and molecular testing into the clinical pathology practice for tumor diagnosis and subsequent selection of the most appropriate therapy.

Keywords: Adenocarcinoma; Molecular testing; Next-generation of sequencing; Squamous cell carcinoma; Targeted therapy.

Figure 1. Histology section-based molecular tests for NSCLC

A. Immunohistochemistry panel: Thyroid transcription factor (TTF-1) is a marker of adenocarcinoma, and p40 (p63) is a marler of squamous cell carcinoma. B. EGFR mutation analysis. C. EML4-ALK fusion fluorescent in situ hybridyzation (FISH) analysis.

Figure 2. Histology subtyping based on treatment algorithm for lung cancer

The utilization of multiplex platforms to test mutations in tumor samples allows testing all NSCLC histologies for panel of mutations and other gene abnormalities regardless of their histology. SCLC, small cell lung cancer; NSCLC, non-small cell lung cancer; NOS, not otherwise specified