Clinical, Pathological, and Molecular Features of Lung Adenocarcinomas with AXL Expression.
The receptor tyrosine kinase AXL is a member of the Tyro3-Axl-Mer receptor tyrosine kinase subfamily. AXL affects several cellular functions, including growth and migration. AXL aberration is reportedly a marker for poor prognosis and treatment resistance in various cancers. In this study, we analyzed clinical, pathological, and molecular features of AXL expression in lung adenocarcinomas (LADs). We examined 161 LAD specimens from patients who underwent pulmonary resections. When AXL protein expression was quantified (0, 1+, 2+, 3+) according to immunohistochemical staining intensity, results were 0: 35%; 1+: 20%; 2+: 37%; and 3+: 7% for the 161 samples. AXL expression status did not correlate with clinical features, including smoking status and pathological stage. However, patients whose specimens showed strong AXL expression (3+) had markedly poorer prognoses than other groups (P = 0.0033). Strong AXL expression was also significantly associated with downregulation of E-cadherin (P = 0.025) and CD44 (P = 0.0010). In addition, 9 of 12 specimens with strong AXL expression had driver gene mutations (6 with EGFR, 2 with KRAS, 1 with ALK). In conclusion, we found that strong AXL expression in surgically resected LADs was a predictor of poor prognosis. LADs with strong AXL expression were characterized by mesenchymal status, higher expression of stem-cell-like markers, and frequent driver gene mutations.
Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Katsuaki
0000-0003-4045-7796
K
Sato
Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Kenichi
K
Suda
Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
Shigeki
S
Shimizu
Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Kazuko
K
Sakai
Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Hiroshi
H
Mizuuchi
Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Kenji
K
Tomizawa
Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Toshiki
T
Takemoto
Department of Genome Biology, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Kazuto
K
Nishio
Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
Tetsuya
T
Mitsudomi
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015820:Cadherins / Q000096:biosynthesis; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D000077156:Gefitinib; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000601:surgery; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D008297:Male; D015999:Multivariate Analysis; D009154:Mutation; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D011799:Quinazolines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D000094963:Axl Receptor Tyrosine Kinase
D000970:Antineoplastic Agents; D015820:Cadherins; D018960:Hyaluronan Receptors; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D000077156:Gefitinib; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human