PMID- 22129856 OWN - NLM STAT- MEDLINE DCOM- 20120906 LR - 20220408 IS - 1872-8332 (Electronic) IS - 0169-5002 (Linking) VI - 76 IP - 3 DP - 2012 Jun TI - Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer: a proposal of diagnostic algorithm for ALK-rearranged adenocarcinoma. PG - 403-9 LID - 10.1016/j.lungcan.2011.11.008 [doi] AB - 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. CI - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved. FAU - Paik, Jin Ho AU - Paik JH AD - Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea. FAU - Choi, Chang-Min AU - Choi CM FAU - Kim, Hyojin AU - Kim H FAU - Jang, Se Jin AU - Jang SJ FAU - Choe, Gheeyoung AU - Choe G FAU - Kim, Dong Kwan AU - Kim DK FAU - Kim, Hwa Jung AU - Kim HJ FAU - Yoon, Hoil AU - Yoon H FAU - Lee, Choon-Taek AU - Lee CT FAU - Jheon, Sanghoon AU - Jheon S FAU - Choe, Ji-Young AU - Choe JY FAU - Chung, Jin-Haeng AU - Chung JH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111130 PL - Ireland TA - Lung Cancer JT - Lung cancer (Amsterdam, Netherlands) JID - 8800805 RN - EC 2.7.10.1 (ALK protein, human) RN - EC 2.7.10.1 (Anaplastic Lymphoma Kinase) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adenocarcinoma/*diagnosis/*genetics/mortality/surgery MH - Adult MH - Aged MH - Aged, 80 and over MH - Algorithms MH - Anaplastic Lymphoma Kinase MH - Early Detection of Cancer MH - Female MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*diagnosis/*genetics/mortality/surgery MH - Male MH - Middle Aged MH - Prognosis MH - Receptor Protein-Tyrosine Kinases/*genetics MH - Risk Factors MH - Survival Analysis MH - *Translocation, Genetic MH - Young Adult EDAT- 2011/12/02 06:00 MHDA- 2012/09/07 06:00 CRDT- 2011/12/02 06:00 PHST- 2011/08/13 00:00 [received] PHST- 2011/10/28 00:00 [revised] PHST- 2011/11/05 00:00 [accepted] PHST- 2011/12/02 06:00 [entrez] PHST- 2011/12/02 06:00 [pubmed] PHST- 2012/09/07 06:00 [medline] AID - S0169-5002(11)00582-4 [pii] AID - 10.1016/j.lungcan.2011.11.008 [doi] PST - ppublish SO - Lung Cancer. 2012 Jun;76(3):403-9. doi: 10.1016/j.lungcan.2011.11.008. Epub 2011 Nov 30.