Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2012-06, Vol.76 (3), p.403-409
• Main Authors: Paik, Jin Ho, Choi, Chang-Min, Kim, Hyojin, Jang, Se Jin, Choe, Gheeyoung, Kim, Dong Kwan, Kim, Hwa Jung, Yoon, Hoil, Lee, Choon-Taek, Jheon, Sanghoon, Choe, Ji-Young, Chung, Jin-Haeng
• Format: Article
• Language: English
• Subjects: ALK; Fluorescence in situ hybridization; Hematology, Oncology and Palliative Medicine; Immunohistochemistry; Non-small cell lung cancer; Prognosis; Pulmonary/Respiratory
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2011.11.008

Abstract Background To characterize the clinicopathologic features of ALK -rearranged lung cancer, and suggest a molecular test protocol for lung adenocarcinoma in the small biopsy specimen. Methods In 735 NSCLC surgical specimens, clinicopathologic features, ALK protein over-expression by immunohistochemistry (IHC), and ALK rearrangement by fluorescence in situ hybridization (FISH) as well as EGFR and KRAS mutation studies were analyzed. Results Of the 735 NSCLC cases, 28 (3.8%) were ALK FISH-positive. ALK rearrangement, EGFR and KRAS mutation were mutually exclusive. ALK rearrangement was significantly higher in adenocarcinomas (6.8%, p < 0.001), younger age ( p < 0.0007), women (7.6%, p < 0.001), and never-smokers (8.9%, p < 0.001) with no gender difference in the adenocarcinoma or never-smoker subgroup. ALK FISH-positivity was not associated with disease recurrence (HR, 0.79; 95% CI, 0.42–1.49) or overall survival (HR, 0.61; 95% CI, 0.24–1.55). However, ALK -rearranged lung cancer tended to show more frequent lymph node metastasis despite its lower T stage. Similar to EGFR -mutated lung cancer, ALK -rearranged lung cancer was enriched in adenocarcinoma, women, and never-smokers. The results of ALK IHC and FISH obtained from tissue microarray (TMA)/biopsy specimens and whole sections after resection were concordant. Conclusion ALK rearrangement was not a significant prognostic factor in surgically resectable NSCLC. The clinical profiles of ALK -rearranged lung cancer patients overlapped with those of EGFR -mutated patients. Therefore, we suggest that simultaneous tests for ALK IHC and EGFR mutation (Chung's SNUBH molecular test protocol), which has important implications for the storage and use of small biopsy or cytology samples for genetic analysis.