Non-Small Cell Lung Carcinoma Biomarker Testing: The Pathologist’s Perspective

Abstract

Biomarker testing has become standard of care for patients diagnosed with non-small cell lung carcinoma (NSCLC). Although, it can be successfully performed in circulating tumor cells, at present, the vast majority of investigations are carried out using direct tumor sampling, either through aspiration methods, which render most often isolated cells, or tissue sampling, that could range from minute biopsies to large resections. Consequently, pathologists play a central role in this process. Recent evidence suggests that refining NSCLC diagnosis might be clinically significant, particularly in cases of lung adenocarcinomas (ADC), which in turn, has prompted a new proposal for the histologic classification of such pulmonary neoplasms. These changes, in conjunction with the mandatory incorporation of biomarker testing in routine NSCLC tissue processing, have directly affected the pathologist’s role in lung cancer work-up. This new role pathologists must play is complex and demanding, and requires a close interaction with surgeons, oncologists, radiologists, and molecular pathologists. Pathologists often find themselves as the central figure in the coordination of a process, that involves assuring that the tumor samples are properly fixed, but without disruption of the DNA structure, obtaining the proper diagnosis with a minimum of tissue waste, providing pre-analytical evaluation of tumor samples selected for biomarker testing, which includes assessment of the proportion of tumor to normal tissues, as well as cell viability, and assuring that this entire process happens in a timely fashion. Therefore, it is part of the pathologist’s responsibilities to assure that the samples received in their laboratories, be processed in a manner that allows for optimal biomarker testing. This article goal is to discuss the essential role pathologists must play in NSCLC biomarker testing, as well as to provide a summarized review of the main NSCLC biomarkers of clinical interest.

Approach to Biomarker Testing: Perspectives from Various Specialties

“…To optimize the analysis of limited tissue available for biomarker testing, communication between the pathologist and the rest of the multidisciplinary team is critical 17 . Thoughtful prioritization of how the tissue sample will be used will help to preserve sufficient biopsy material for molecular analysis and ensure rapid diagnosis 18 .…”

Targeted Therapies for Non-Small Cell Lung Cancer: An Update on Epidermal Growth Factor Receptor and Anaplastic Lymphoma Kinase Inhibitors

“…Considering the impact of targeted therapies and molecular testing from patient perspectives is useful. Before undergoing molecular testing, patients need to be made aware of the relatively low individual likelihood of obtaining a positive result for either an activating EGFR mutation (about 15% of primary lung adenocarcinoma) or ALK rearrangement (2%-6% of patients with NSCLC) (Brega & Brandao, 2014). Patients should be advised that current targeted therapies are not curative and that all of these lung cancers are eventually expected to develop resistance to the treatment.…”

The accelerated path of ceritinib: Translating pre-clinical development into clinical efficacy

“…Several other variants of ALK rearrangements have subsequently been identified in NSCLC, all resulting in constitutive activation [6]. Approximately 2-6% of NSCLC patients exhibit ALK-positive (ALK+) NSCLC [7], with higher rates observed in a clinically enriched (younger, neversmokers [8][9][10]) population of adenocarcinoma patients.…”