-EGFR mutations and anaplastic lymphoma kinase (ALK) translocations have significant biologic and therapeutic implications in lung cancers, particularly lung adenocarcinomas.
-The National Cancer Care Network and the combined College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology guidelines indicate that all lung adenocarcinomas (ADCs) should be tested for epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements.
104 consecutively resected lung adenocarcinomas from 396 non-smoker females (less than 100 cigarettes in a lifetime) at a single institution (Tongji University, Shanghai, China) were analyzed for mutations in EGFR, EML4-ALK, KRAS, HER2, BRAF, and PIK3CA.
ALK FISH testing was performed on 129 lung adenocarcinomas from 71 cytology cases and 58 biopsy/resection specimens using Papanicolaou staining with integrated cytomorphology.
ALK-positive patients showed a greater RR and longer PFS with pemetrexed-based therapy than patients without ALK rearrangements, suggesting that pemetrexed should be preferentially considered for the treatment of ALK-positive lung adenocarcinoma when use of crizotinib is not feasible.
ALK fusions were positively associated with a micropapillary pattern (P = .002) and were negatively associated with a lepidic pattern (P = .008) in an expanded statistical analysis of 900 individual adenocarcinoma components, although they appeared to be more common in acinar-predominant LADCs in the analysis of 629 patients.
ALK fusion-positive tumors were significantly different in tumor stage, central location, SUV(max), homogeneity on 1-, 2-, and 3-voxel distances, and sum mean on 2-voxel distance compared with ROS1/RET fusion-positive tumors.ALK/ROS1/RET fusion-positive lung adenocarcinomas possess certain clinical and imaging features that enable good discrimination of fusion-positive from fusion-negative lung adenocarcinomas.
Anaplastic lymphoma kinase (ALK)-expressing Lung Adenocarcinoma with Combined Neuroendocrine Component or Neuroendocrine Transformation: Implications for Neuroendocrine Transformation and Response to ALK-tyrosine Kinase Inhibitors.
Anaplastic lymphoma kinase ( ALK) gene rearrangements are found in approximately 5% of lung adenocarcinomas and are associated with specific clinical features including a high risk of brain metastases.