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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.

plos one

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