Takaoki Furukawa1, Yoshihiro Miyata1, Kei Kushitani2, Takahiro Mimae1, Yasuhiro Tsutani1, Yukio Takeshima2, Morihito Okada3. 1. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima. 2. Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. 3. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima morihito1217@gmail.com.
Abstract
OBJECTIVE: High maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography are associated with inferior survival in non-small cell lung cancer. Here, we investigated the biological mechanisms underlying [(18)F]-fluoro-2-deoxyglucose uptake in non-small cell lung cancer. METHODS: This study included 133 patients with non-small cell lung cancer (109 with adenocarcinoma and 24 with squamous cell carcinoma). The patients underwent tumour resection, at the latest, 4 weeks after [(18)F]-fluoro-2-deoxyglucose positron emission tomography. The maximum standardized uptake values for primary lesions were calculated based on [(18)F]-fluoro-2-deoxyglucose uptake. The expression of hypoxia-inducible factor 1α and glucose transporter 1 was evaluated on immunostained tumour sections using six-point grading scales. RESULTS: Maximum standardized uptake values and the expression of hypoxia-inducible factor 1α and glucose transporter 1 were significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.001, P = 0.034 and P < 0.001, respectively). In adenocarcinoma, but not squamous cell carcinoma, maximum standardized uptake values, hypoxia-inducible factor 1α and glucose transporter 1 correlated with various clinicopathological factors relating to malignancy, and maximum standardized uptake values and glucose transporter 1 were associated with disease-free survival (P < 0.001 and P = 0.029) and overall survival (P < 0.001 and P = 0.033, respectively). Patients with high expression of hypoxia-inducible factor 1α tended to exhibit shorter disease-free survival and overall survival than those with low expression, but the differences were not significant (P = 0.32 and P = 0.15, respectively). And then in adenocarcinoma, hypoxia-inducible factor 1α and glucose transporter 1, glucose transporter 1 and maximum standardized uptake values, and hypoxia-inducible factor 1α and maximum standardized uptake values were significantly correlated (P < 0.001 for all), suggesting that hypoxia-inducible factor 1α-induced glucose transporter 1 might influence maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography. CONCLUSIONS: In lung adenocarcinoma, but not squamous cell carcinoma, hypoxia-inducible factor 1α and glucose transporter 1 expressions indicate tumour aggressiveness pathologically and might explain high [(18)F]-fluoro-2-deoxyglucose uptake on positron emission tomography and correlate with poor prognosis.
OBJECTIVE: High maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography are associated with inferior survival in non-small cell lung cancer. Here, we investigated the biological mechanisms underlying [(18)F]-fluoro-2-deoxyglucose uptake in non-small cell lung cancer. METHODS: This study included 133 patients with non-small cell lung cancer (109 with adenocarcinoma and 24 with squamous cell carcinoma). The patients underwent tumour resection, at the latest, 4 weeks after [(18)F]-fluoro-2-deoxyglucose positron emission tomography. The maximum standardized uptake values for primary lesions were calculated based on [(18)F]-fluoro-2-deoxyglucose uptake. The expression of hypoxia-inducible factor 1α and glucose transporter 1 was evaluated on immunostained tumour sections using six-point grading scales. RESULTS: Maximum standardized uptake values and the expression of hypoxia-inducible factor 1α and glucose transporter 1 were significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.001, P = 0.034 and P < 0.001, respectively). In adenocarcinoma, but not squamous cell carcinoma, maximum standardized uptake values, hypoxia-inducible factor 1α and glucose transporter 1 correlated with various clinicopathological factors relating to malignancy, and maximum standardized uptake values and glucose transporter 1 were associated with disease-free survival (P < 0.001 and P = 0.029) and overall survival (P < 0.001 and P = 0.033, respectively). Patients with high expression of hypoxia-inducible factor 1α tended to exhibit shorter disease-free survival and overall survival than those with low expression, but the differences were not significant (P = 0.32 and P = 0.15, respectively). And then in adenocarcinoma, hypoxia-inducible factor 1α and glucose transporter 1, glucose transporter 1 and maximum standardized uptake values, and hypoxia-inducible factor 1α and maximum standardized uptake values were significantly correlated (P < 0.001 for all), suggesting that hypoxia-inducible factor 1α-induced glucose transporter 1 might influence maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography. CONCLUSIONS: In lung adenocarcinoma, but not squamous cell carcinoma, hypoxia-inducible factor 1α and glucose transporter 1 expressions indicate tumour aggressiveness pathologically and might explain high [(18)F]-fluoro-2-deoxyglucose uptake on positron emission tomography and correlate with poor prognosis.