ALK immunohistochemistry is highly sensitive and specific for the detection of ALK translocated lung adenocarcinomas: lessons from an audit of lung cancer molecular testing

• Main Authors: YC Kheng, K Walsh, L Williams, WA Wallace, DJ Harrison, A Oniscu
• Format: Article
• Language: English
• Published: Royal College of Physicians of Edinburgh 2018-03-01
• Series: The Journal of the Royal College of Physicians of Edinburgh
• Subjects: ALK; EGFR; KRAS; lung adenocarcinomas; molecular pathology
• Online Access: https://www.rcpe.ac.uk/sites/default/files/jrcpe_48_1_oniscu.pdf

Background The approval of novel targeted treatments for epidermal growth factor receptor (EGFR)-positive and anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer has led to the increased requirement for mutation testing. Results We report our experience of ALK testing with immunohistochemistry (IHC) and fluorescence in-situ hybridisation (FISH) and present the prevalence of EGFR, Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) and ALK mutations. From January 2011 to May 2014, we found mutation rates of EGFR, KRAS and ALK to be 10.4% (67/643), 35.8% (86/240) and 2.3% (7/304), respectively. ALK-rearrangements were found to be associated with never smokers (p < 0.001) and younger patients (≤ 50 years old) (p < 0.001). ALK IHC protein expression in tumour cells is 100% sensitive (7 IHC+/7 FISH+) and 96.6% specific (113 IHC-/117 FISH-) for ALK-rearrangements by FISH. ALK-rearranged tumours were wild-type for EGFR and KRAS. Conclusion Our findings support the use of ALK protein expression and KRAS mutation testing as part of the molecular diagnostic algorithm for lung adenocarcinomas.