Elsevier

Lung Cancer

Volume 72, Issue 2, May 2011, Pages 191-198
Lung Cancer

Assessment of factors influencing FDG uptake in non-small cell lung cancer on PET/CT by investigating histological differences in expression of glucose transporters 1 and 3 and tumour size

https://doi.org/10.1016/j.lungcan.2010.08.017Get rights and content

Abstract

Purpose

The objective of this study was to evaluate the major factors influencing on FDG uptake in non-small cell lung cancer (NSCLC) by investigating histological difference in the expression of glucose transporters 1 and 3 (Glut-1 and Glut-3) and tumour size.

Methods

This study enrolled 32 patients including 9 with squamous cell carcinoma (SCC) and 23 with adenocarcinoma (AC). The AC cases comprised 16 AC with mixed subtypes (AC-mixed) and 7 localized AC in situ (localized bronchioloalveolar carcinoma). Partial volume effect corrected maximum standardized uptake values (cSUVmax) and tumour size were obtained using FDG PET/CT. Glut-1 and Glut-3 expression were evaluated using five-point grading scales.

Results

Overexpression of Gluts was observed at high rates (88% for Glut-1 and 97% for Glut-3). They were mutually correlated. cSUVmax showed better correlation with size than with Gluts overexpression. AC and SCC showed a high positive expression rate for both Glut-1 and Glut-3, although the degree of overexpression was significantly higher in SCC than AC. In addition, localized AC in situ revealed a considerably higher positive expression rate and similar degrees of overexpression for both Glut-1 and Glut-3 compared with AC-mixed. By contrast, localized AC in situ alone was significantly smaller in both cSUVmax and size than either SCC or AC-mixed. No significant difference was found in cSUVmax or size between SCC and AC-mixed.

Conclusions

The FDG uptake of NSCLC might be dependent on size rather than on overexpression of Glut-1 or Glut-3. Low FDG uptake in localized AC in situ might result from its small size rather than Glut overexpression.

Introduction

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related deaths worldwide [1]. Recently, PET/CT using the glucose analogue F-18 fluorodeoxyglucose (FDG) has been reported to provide functional and morphologic images in a single examination [2], [3]. It is necessary for clinical management of non-small cell lung cancer (NSCLC). However, the factors influencing the FDG uptake of the primary tumour have not been clarified yet. Increased glucose consumption and glycolytic activity have been reported in NSCLC [4]. The uptake mechanism and biochemical pathways of F-18 FDG have been studied in vitro and in vivo, and glucose transport through the cell membrane via glucose transporters (Gluts) has been reported as an important factor to increase FDG uptake in malignant tumours [5], [6], [7], [8]. Many reports in the relevant literature describe the relation between FDG uptake and the respective expressions of Glut-1 and Glut-3. Several authors reported that FDG uptake correlated well with overexpression of Glut-1 and/or Glut-3 in NSCLC [9], [10], [11], [12], [13]; other investigators reported contradictory findings [14], [15]. Brown et al. reported that expression of Glut-3 was not observed in NSCLC and concluded that FDG uptake was dependent upon tumour size [14]. Consequently, the major factor influencing FDG uptake in NSCLC remains controversial.

An important advantage of PET/CT is that it enables evaluation of the tumour size precisely using high-resolution CT imaging; it also provides an accurate quantitative assessment of FDG uptake.

This study was conducted to clarify the major factors influencing FDG uptake of NSCLC using PET/CT imaging by comparing histological differences in the expression of Glut-1 and Glut-3 and tumour size, particularly addressing localized form of bronchioloalveolar carcinoma (BAC). In the near future, the term “bronchioloalveolar carcinoma” is supposed to be replaced by “adenocarcinoma in situ”. Therefore, we adopted the term ‘adenocarcinoma (AC) in situ’ instead of BAC in the present study.

Section snippets

Subjects

This prospective study was approved by our institutional review board. Written informed consent was obtained from each patient.

Patients with NSCLC who underwent FDG PET/CT examination within 1 month before surgery and who agreed to undergo examination with Glut staining were included in the study.

Exclusion criteria were the following: (1) patients who had received any prior anticancer therapy, (2) patients with diabetes mellitus or a high serum glucose level (greater than 150 mg/dL) at the time

Patients

During December 2005 through October 2008, 36 patients with NSCLC underwent FDG PET/CT examination within 1 month before surgery and agreed to participate in this study. Four patients were excluded (one for a high serum glucose level of 170 mg/dl, two for adenosquamous cell carcinoma, and one for large cell neuroendocrine carcinoma). Consequently, 32 patients (18 males, 14 females, range 45–81 years, median age 68 years) were included in this study.

The histological types were SCC in 9 patients

Discussion

The results obtained from this study are summarized as follows:

  • Overexpression of Glut-1 and Glut-3 was observed equally at high rates and their grades correlated well mutually in NSCLC.

  • FDG uptake (cSUVmax) correlated better with tumour size than with overexpression of either Glut-1 or Glut-3.

  • AC showed positive expression at a high rate, as did SCC, for both Glut-1 and Glut-3, although the degree of overexpression was significantly higher for SCC than for AC. Furthermore, localized AC in situ

Conclusion

The FDG uptake of NSCLC might be dependent on tumour size rather than overexpression of Glut-1 or Glut-3. The positive expressions of Glut-1 and Glut-3 were observed equally at high rates for SCC, AC-mixed, and localized AC in situ, although the grade of expression of each Glut was highest for SCC. For localized AC in situ, both FDG uptake and tumour size were significantly lower than for lung cancers of the other two types. Results may suggest that low FDG uptake in localized AC in situ was

Conflict of interest statement

None declared.

Acknowledgements

The authors wish to extend special thanks to Shigeki Kobayashi MD and Koichiro Yamakado MD and Nobuyoshi Matsushima MD (Department of Radiology, Mie University School of Medicine) for discussion of related ideas, and Naoki Nagasawa MSc and Yoshikazu Yamao MSc (Central Department of Radiology, Mie University Hospital) for technical suggestions related to FDG PET/CT data acquisition.

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