A Comprehensive Comparative Analysis of the Histomorphological Features of ALK-Rearranged Lung Adenocarcinoma Based on Driver Oncogene Mutations: Frequent Expression of Epithelial-Mesenchymal Transition Markers than Other Genotype

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Kim, Hyojin; Jang, Se Jin; Chung, Doo Hyun; Yoo, Seol Bong; Sun, Pingli; Jin, Yan; Nam, Kyung Han; Paik, Jin-Ho; Chung, Jin-Haeng

Issue Date
Public Library of Science
PLoS ONE, Vol.8 No.10, p. e76999
Molecular classification of lung cancer correlates well with histomorphological features. However, specific histomorphological features that differentiate anaplastic lymphoma kinase (ALK)-rearranged tumors from ALK-negative tumors have not been fully evaluated. Eighty ALK-rearranged and 213 ALK-negative (91 epidermal growth factor receptor-mutated; 29 K-ras-mutated; 93 triple-negative) resected lung adenocarcinomas were analyzed for several histomorphological parameters and histological subtype. ALK-rearranged tumors were associated with younger age at presentation, frequent nodal metastasis, and higher stage of disease at diagnosis. ALK-rearranged tumors were more likely to show a solid predominant pattern than ALK-negative tumors (43.8%; 35/80; p>0.001). Unlike ALK-negative tumors, a lepidic predominant pattern was not observed in ALK-rearranged tumors (p>0.001). In multivariate analysis, the most significant morphological features that distinguished ALK-rearranged tumors from ALK-negative tumors were cribriform formation (odds ratio [OR], 3.253; p=0.028), presence of mucin-containing cells (OR, 4.899; p=0.008), close relationship to adjacent bronchioles (OR, 5.361; p= 0.001), presence of psammoma bodies (OR, 4.026; p=0.002), and a solid predominant pattern (OR, 13.685; p=0.023). ALK-rearranged tumors exhibited invasive histomorphological features, aggressive behavior and frequent expression of epithelial-mesenchymal transition markers (loss of E-cadherin and expression of vimentin) compared with other genotype (p=0.015). Spatial proximity between bronchus and ALK-rearranged tumors and frequent solid histologic subtype with p63 expression may cause diagnostic difficulties to differentiate squamous cell carcinoma in the small biopsy, whereas p40 was rarely expressed in ALK-rearranged adenocarcinoma. Knowledge of these features may improve the diagnostic accuracy and lead to a better understanding of the characteristic behavior of ALK-rearranged tumors.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Biomedical Sciences (대학원 의과학과)Journal Papers (저널논문_의과학과)
College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Journal Papers (저널논문_의학과)
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