National Working Group Meeting on ALK diagnostics in lung cancer

Abstract

The global landscape of molecular testing is rapidly changing, with the recent publication of the International Association for the Study of Lung Cancer (IASLC)/College of American Pathologists (CAP) guidelines and the ALK Atlas. The IASLC/CAP guidelines recommend that tumors from patients with non-small cell lung cancer (NSCLC) be tested for ALK rearrangements in addition to epidermal growth factor receptor (EGFR) mutations. The spur for this recommendation is the availability of novel therapies that target these rearrangements. This article is based on coverage of a

ALK‐rearrangement in non‐small‐cell lung cancer (NSCLC)

“…The principle of IHC is based on the fact that activating ALK rearrangements are accompanied by significant overexpression of the catalytic portion of this tyrosine kinase. IHC is generally capable of producing highly reliable results when performed in reference laboratories; however, it requires the standardization of reagents and protocols across pathology laboratories . The Ventana ALK assay used D5F3 antibody is a resultful method of detecting ALK rearrangement.…”

“…IHC is generally capable of producing highly reliable results when performed in reference laboratories; however, it requires the standardization of reagents and protocols across pathology laboratories. [55][56][57][58] The Ventana ALK assay used D5F3 antibody is a resultful method of detecting ALK rearrangement. The Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems, Tucson, AZ, USA) was approved by the US FDA in 2015 as a companion detection test for the use of crizotinib.…”

Novel ALK fusion partners in lung cancer

“…FISH requires significant time input of an extensively trained personnel and cannot be subjected to a reasonable automation; furthermore, it demonstrates relatively high failure rates at least in some sample series and may provide poorly interpretable results in a noticeable fraction of NSCLC cases. In addition, FISH always relies on the purchase of commercial kits, which are highly expensive [2,[6][7][8][9][10][11].…”

“…The principle of IHC is based on the fact that activating ALK rearrangements are accompanied by significant overexpression of the catalytic portion of this tyrosine kinase. IHC is generally capable to produce highly reliable results when performed in reference laboratories, however its interlaboratory reproducibility and performance in heterogenous lung cancer tissue collections remains to be evaluated [8,9,[11][12][13][14]. Use of PCR-based assays is also a common approach for ALK testing.…”

ALK and ROS1 Double-Rearranged Lung Squamous Cell Carcinoma Responding to Crizotinib Treatment: A Case Report

“…ALK rearrangement occurs in approximately 5% of all lung adenocarcinomas and 1.3% of lung squamous cell cancer (SqCC), whereas ROS1 rearrangement accounts for 1% to 3% of all lung adenocarcinomas and rarely, has been reported in lung SqCC. 1,2 Crizotinib has been approved by the U.S. Food and Drug Administration for treating patients with advanced-stage ALK-positive or ROS1-positive NSCLCs. Some case reports have also shown that patients with lung SqCC with ALK or ROS1 rearrangements respond to crizotinib treatment.…”