1180PD - Expression of hypoxia-induced factor 1α and glucose transporter 1 correlates with [18F]-fluoro-2-deoxy-glucose uptake on positron emission tomograp...

Date 29 September 2012
Event ESMO Congress 2012
Session NSCLC - Immunotherapy, SCLC and Mesothelioma
Topics Non-Small-Cell Lung Cancer, Early Stage
Translational Research
Presenter Yoshihiro Miyata
Authors Y. Miyata1, T. Furukawa2, Y. Tsutani2, T. Mimae2, K. Misumi2, T. Yoshiya2, Y. Ibuki2, M. Okada2
  • 1Surgical Oncology Dept., Hiroshima University, 7348551 - Hiroshima/JP
  • 2Surgical Oncology, Hiroshima University, 7348551 - Hiroshima/JP

Abstract

Background

High maximal standardized uptake values (SUVmax) on [18F]-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) are associated with inferior survival in lung adenocarcinoma. However, the exact mechanisms are unknown. Here, we investigated the biological mechanisms underlying FDG uptake in different subtypes of adenocarcimomas.

Methods

This retrospective study included 287 patients with adenocarcinoma (166 with Stage IA). The patients underwent systematic tumor resection at Hiroshima University Hospital from January 2007 to December 2011, at the latest, 4 weeks after FDG-PET. The SUVmax values for primary lesions were calculated based on FDG uptake. Tumors were subdivided according to each morphologic growth pattern. The expression of hypoxia-inducible factor 1α (HIF1α) and glucose transporter 1 (GLUT1) was evaluated in 70 patients with 147 histologic subtypes using immunostaining.

Results

There were significant differences in SUVmax and disease-free survival (DFS) among different histologic subtypes. Mean SUVmax and 5-year DFS were 0.90 and 100% in is situ (n = 41), 1.1 and 100% in minimally invasive (n = 5), 1.8 and 94.3% in lepidic (n = 66), 3.9 and 75.2% in papillary (n = 136), 5.4 and 91.7% in acinar (n = 26), and 7.6 and 71.6% in solid (n = 13) predominant subtypes. HIF1α and GLUT1, and GLUT1 and SUVmax were significantly correlated (p < 0.001 for both) in adenocarcinoma. Moreover, the expressions of HIF1α and GLUT1 correlated with various clinicopathological factors relating to malignancy, such as pathological stage (I vs. II + III; p = 0.014), lymph node metastasis (p = 0.037), pleural invasion (p = 0.0093), lymphatic invasion (p < 0.001), and venous invasion (p < 0.001). GLUT1 and SUVmax were jointly associated with DFS (p = 0.0098 and p < 0.001, respectively in adenocarcinoma). There were significant differences in HIF1α and GLUT1 expression among different histologic subtypes. Mean HIF1α and GLUT1score were 0 and 0.15 in is situ (n = 13), 0.03 and 0.11 in lepidic (n = 36), 0.19 and 1.0 in papillary (n = 52), 0.47 and 1.2 in acinar (n = 34), 0.11 and 1.6 in micropapillary (n = 9), and 2.3 and 3.0 in solid (n = 3) subtypes.

Conclusions

In different histologic subtypes of lung adenocarcinomas, HIF1α-induced GLUT1 expression might explain high FDG uptake on PET and correlate with poor prognosis.

Disclosure

All authors have declared no conflicts of interest.