Impact of GLUT1 and Ki-67 expression on early‑stage lung adenocarcinoma             diagnosed according to a new international multidisciplinary classification.
High expression levels of glucose transporter isoform 1 (GLUT1) and Ki-67             are reportedly associated with malignancy-related clinicopathological factors             in malignant tumors. Recently, a new histological IASLC/ATS/ERS classification             for lung adenocarcinoma was proposed. In this study, we investigated the clinicopathological             impact of GLUT1 and Ki-67 expression on early-stage lung adenocarcinoma classified             according to the IASLC/ATS/ERS classification. One hundred and five patients with             completely resected stage IA lung adenocarcinoma were retrospectively classified             into two groups, a 'non-invasive type' (n=31) or an 'invasive type' (n=74), based             on the IASLC/ATS/ERS classification. GLUT1 and Ki-67 expression status was evaluated             using immunohistochemistry. The epidermal growth factor receptor (EGFR) and KRAS             mutation status was determined using PCR-based assays. Positive GLUT1 and Ki-67             expression and EGFR and KRAS mutations were detected in 28 (27%), 33 (31%), 51 (49%)             and 5 (8%) cases, respectively. Positive GLUT1 expression was significantly associated             with a wild-type EGFR and mutant KRAS status. A multivariate analysis revealed             that positive GLUT1 expression was independently associated with the 'invasive             type'. In multivariate analyses for overall survival (OS) and disease-free survival             (DFS), positive Ki-67 and GLUT1 expression was the only independent factor for             a poor OS (P=0.012) and DFS (P=0.040), respectively. In addition, when stratified             according to the GLUT1 and Ki-67 status, double-positive cases had the poorest             DFS and OS times, compared with the other categories. Positive GLUT1 expression             is associated with the invasive character of early-stage lung adenocarcinoma and             with early disease relapse. Our results strongly suggest that GLUT1 and Ki-67             play important roles in acquiring biological malignant potential in early-stage             lung adenocarcinoma.
Department of Thoracic Surgery, Okayama University Hospital,                     Okayama, Japan.
Yuho
Y
Maki
Junichi
J
Soh
Kouichi
K
Ichimura
Kazuhiko
K
Shien
Masashi
M
Furukawa
Takayuki
T
Muraoka
Norimitsu
N
Tanaka
Tsuyoshi
T
Ueno
Hiromasa
H
Yamamoto
Hiroaki
H
Asano
Kazunori
K
Tsukuda
Shinichi
S
Toyooka
Shinichiro
S
Miyoshi
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007390:International Agencies; D019394:Ki-67 Antigen / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009367:Neoplasm Staging / Q000145:classification*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; D051272:Glucose Transporter Type 1; C117307:KRAS protein, human; D019394:Ki-67 Antigen; D011518:Proto-Oncogene Proteins; C495677:SLC2A1 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins