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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
the College of American Pathologists (CAP)/International Association for the Study of Lung Cancer (IASLC)/Association for Molecular Pathology (AMP), have recommended that ALK testing not be routinely performed on advanced NSCLC with squamous histology (Lindeman 2013). (See Appendix 2 and Chapter 9 for a complete discussion of guidelines for ALK testing.) However, ALK rearrangement has been detected in approximately 1.3% of more than 1,400 squamous cell lung carcinomas (Appendix 1) and in several case reports in which ALK rearrangement was verified by IHC (Alrifai 2013, An 2013, Ochi 2013). The discordance among studies of squamous cell lung carcinoma may be caused by the difficulties that still exist in diagnosing histologic subtypes of NSCLC. A lung cancer diagnosis is often made according to the examination of a small biopsy specimen or cytology samples, but histopathologic diagnoses made on small biopsy specimens are not always representative of the whole tumor. Reassessment of a squamous cell cancer diagnosis in such specimens with no evidence of EGFR and KRAS mutations demonstrated components of adenocarcinoma in 15 of 16 tumors (Rekhtman 2012). Therefore, the CAP/IASLC/AMP guideline suggests that ALK testing be done only for patients with adenocarcinomas and mixed lung cancers with an adenocarcinoma component in the setting of a fully excised lung cancer specimen. ALK testing is also recommended for limited specimens, such as biopsy and cytology specimens, where an adenocarcinoma component cannot be completely excluded. Screening for ALK with IHC may represent an ideal solution to the concerns of ALK testing in squamous cell lung carcinoma. Considering its low cost and high reproducibility, sensitivity, and specificity, IHC testing is conceivable for patients with squamous cell lung carcinoma, with FISH, which is more expensive, used to confirm positive results of IHC. For patients with localized or local-regional NSCLC, testing for ALK rearrangement is not currently associated with any immediate therapeutic consequences. However, ALK testing may be beneficial, as many of these patients will subsequently have disease recurrence, and the test results may save time and effort later on.