Any Place for Immunohistochemistry within the Predictive Biomarkers of Treatment in Lung Cancer Patients?

Abstract

The identification of certain genomic alterations (EGFR, ALK, ROS1, BRAF) or immunological markers (PD-L1) in tissues or cells has led to targeted treatment for patients presenting with late stage or metastatic lung cancer. These biomarkers can be detected by immunohistochemistry (IHC) and/or by molecular biology (MB) techniques. These approaches are often complementary but depending on, the quantity and quality of the biological material, the urgency to get the results, the access to technological platforms, the financial resources and the expertise of the team, the choice of the approach can be questioned. The possibility of detecting simultaneously several molecular targets, and of analyzing the degree of tumor mutation burden and of the micro-satellite instability, as well as the recent requirement to quantify the expression of PD-L1 in tumor cells, has led to case by case development of algorithms and international recommendations, which depend on the quality and quantity of biological samples. This review will highlight the different predictive biomarkers detected by IHC for treatment of lung cancer as well as the present advantages and limitations of this approach. A number of perspectives will be considered.

Immunohistochemistry for Diagnosis of Metastatic Carcinomas of Unknown Primary Site

“…There is a need for an efficient diagnostic screening algorithm method of molecular alterations using IHC. IHC may provide an efficient screening tool for “druggable” genomic alterations by taking advantage of a growing list of available mutation-specific antibodies (i.e., ALK rearrangements, D5F3 and 5A4 clones; ROS1 rearrangements, clone D4D6; BRAF V600E mutation, clone VE1; EGFR exon 19 E746_A750del, 6B6 clone; EGFR exon 21 L858R mutation, 43B2 clone) [ 78 , 79 ]. Recently, PD-1 and PD-L1, detected by IHC, have been identified as immune therapy biomarkers in various solid malignancies including CUPs, which may open up an unexplored avenue for treatment with anti-PD-1/PD-L1 antibodies in these patients [ 80 , 81 ].…”

CSF1R-Expressing Tumor-Associated Macrophages, Smoking and Survival in Lung Adenocarcinoma: Analyses Using Quantitative Phosphor-Integrated Dot Staining

“…Lung adenocarcinoma represents a group of clinicopathologically and molecularly heterogeneous diseases [ 23 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ]. A history of smoking substantially affects the molecular features of these tumors.…”

Non–small cell lung cancer predictive biomarker testing via immunocytochemistry: Ways of future past?

“…Given the backdrop of rapid change in thoracic oncology and resulting increased testing complexity in this era of personalized medicine, it behooves the cytopathologist to actively participate in a process that has been described as “personalized sample management.” The tumor cell quality, quantity, and purity can greatly vary from specimen to specimen. When considering relevant clinicopathologic features as well as the medical urgency dictated by the clinical status of the patient, the cytopathologist as part of the clinical care team is best situated to enter into discussions with the oncologist to decide if and how to deviate from standard testing algorithms, for instance deciding when to use focused biomarker ICC testing as outlined in the accompanying paper by Jain et al…”