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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
Table 1. Guidelines or Recommendations Published by Various Expert Groups on ALK Testing in Lung Cancer
Author, Year Organiztion Methods Discussed Diagnosis Algorithm Testing of Cytology Samples Immunohistochemistry (IHC)
Mitsudomi et al., 2011
JLCS
FISH, IHC, and RT-PCR
IHC screening followed by confirmation with FISH
Suitable, with recommendation to make a cell block for FISH and IHC
Recommendation to submit samples to validated commercial labs where appropriate clones and detection system are used Not discussed
Garrido et al., 2012
SEOM and SEAP
FISH FISH, IHC, and RT-PCR FISH and IHC
FISH testing for patients Not discussed with EGFR-negative tumors IHC screening followed by confirmation with FISH IHC screening followed by confirmation with FISH
Thunnissen Experts in et al., Europe 2012b Yi et al., 2012 Marchetti et al., 2013 Lindeman et al., 2013 Experts AIOM and SIAPEC-IAP CAP-IASLCAMP
Histologic and Has considerable cytologic potential as a specimens are both screening tool potentially suitable Not discussed FISH is applicable, including on smears Suitable, with cell blocks preferred over smear preparations May be a practical and reliable screening tool May be used for screening, but insufficient data to draw definitive conclusions Properly validated method may be a screening tool to select specimens for ALK FISH testing; FISH not needed if results with optimized IHC are negative
FISH, IHC, FISH for selection of and RT-PCR patients with stage (frozen tissue) IIIB and IV NSCLC FISH FISH at time of diagnosis for patients with advanced lung adenocarcinoma (or NSCLS with adenocarcinoma component); testing for patients with stage I-III NSCLC is encouraged but should be decided by local multidisciplinary team FISH is standard; may screen with IHC and confirm positive results with FISH; PCR being evaluated
Ettinger et al., 2013
NCCN
FISH
Not discussed
May be used as screening tool; IHC assays for lymphoma are inadequate for the detection of most ALK-rearranged NSCLCs
ESMO = European Society for Medical Oncology, SEOM = Spanish Society of Medical Oncology, SEAP: Spanish Society of Pathology, AIOM = Italian Association of Medical Oncology, SIAPEC-IAP = Italian Society of Anatomic Pathology and Diagnostic Cytopathology-International Academy of Pathology, NCCN = National Comprehensive Cancer Network, ALCL = anaplastic large cell lymphoma.
consensus opinion in the CAP/IASLC/AMP guideline is that validation of ALK testing should follow the same guidelines and similar quality control/assurance policies as for other molecular diagnostic testing. To implement standardization across laboratories, several multicenter studies with this goal have been conducted across different countries or regions of the world (Table 2). Europe The ETOP Lungscape project is designed to address biomarker research in lung cancer. The first protocol was a retrospective cohort study of ALK gene rearrangement to address the prevalence of ALK positivity in resected stage I-III lung adenocarcinomas in Europe using IHC followed by FISH for confirmation (Blackhall 2012). An ALK IHC protocol was validated in a round-robin test with 15 laboratories. Although the antibody clone used was 5A4, in conjunction with the Novolink detection system (Leica Biosystems), some laboratories used the Bond-Max autostainer platform (Leica Biosystems) and others performed manual staining. An interim analysis demonstrated that ALK IHC