FDG uptake and glucose transporter type 1 expression in lymph nodes of non-small cell lung cancer

Chung, Jin-Haeng; Lee, Won Woo; Park, S.Y.; Choe, Gheeyoung; Sung, Sook-Whan; Lee, M.C.; Kim, S.E.

doi:10.1016/j.ejso.2006.05.017

Cited by 17 publications

(13 citation statements)

References 15 publications

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“…The current study showed that GLUT1 was expressed exclusively in lymphoid follicles, as has been found by other investigators (8,9). The identical staining pattern found between GLUT1 and CD21 suggests that FDCs in lymphoid follicles express GLUT1 but does not indicate, however, that 18 F-FDG accumulates in all lymphoid follicles harboring FDCs, because the number of total follicles was not associated with nodal SUVmax.…”

Section: Discussionsupporting

confidence: 63%

“…In previous articles, GLUT1 expression in lymphoid follicles was reported in mediastinal lymphadenopathy of lung cancer patients, which the authors concluded was a major cause of false-positive findings on PET/ CT for nodal staging of lung cancer (8,9). The semiquantitative standardized uptake value (SUV) in lymph nodes, however, did not correlate with the area and grade of GLUT1 expression (9). Lymphoid follicles are composed of lymphocytes, macrophages, and follicular dendritic cells (FDCs).…”

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confidence: 99%

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¹⁸F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

Nakagawa¹,

Yamada²,

Suzuki³

2008

J Nucl Med

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PET using 18 F-FDG is acceptable as a preoperative diagnostic tool for head and neck cancer. PET combined with CT provides precise localization of neck lymph nodes. Reactive lymphadenopathy is well known as a principal cause of false-positive findings on PET/CT for nodal staging. We investigated the reactive lymph nodes of oral cancer to elucidate the 18 F-FDG-avid area in these nodes. Methods: Surgically dissected neck lymph nodes of oral cancer were retrospectively reviewed. Of the patients without pathologic nodal metastasis who underwent preoperative PET/CT, 11 patients with 31 enlarged lymph nodes at 20 levels were enrolled. The maximum standardized uptake value (SUVmax) of each lymph node was recorded. The diameters of the long and short axes were measured by pathologic sectioning, and the sectional surface area was calculated in square millimeters. Besides being stained with hematoxylin and eosin, the sections were immunohistochemically stained by CD79a for B cells, CD3 for T cells, CD68 for macrophages, CD21 for follicular dendritic cells (FDCs), and ubiquitous glucose transporter type 1 (GLUT1). The expression of GLUT1 was compared with staining of lymphoid cells. The numbers of total lymphoid follicles and hyperplastic secondary follicles were counted on CD21 and hematoxylin and eosin sections, respectively. The follicular reactivity index was determined as the ratio of secondary follicles relative to total follicles on the corresponding section. These parameters of reactive lymph nodes were analyzed on a level basis. Results: GLUT1 was expressed exclusively in lymphoid follicles, whose staining pattern was identical to that of FDCs. The calculated sectional area correlated significantly with the number of total follicles (r 5 0.560; P 5 0.0101). SUVmax did not correlate with the number of total follicles (P 5 0.8947) but correlated significantly with the number of secondary follicles (r 5 0.535; P 5 0.0152). In addition, a strong positive correlation between SUVmax and the follicular reactivity index was demonstrated (r 5 0.829; P , 0.0001). Conclusion: GLUT1 was expressed on cytoplasmic protrusions of FDCs in lymphoid follicles. The 18 F-FDG accumulation in reactive lymphadenopathy depended on secondary follicles. FDCs in germinal centers of secondary follicles are suggested to be avid for 18 F-FDG and the principal cause of false-positive findings for nodal staging.

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Section: Discussionsupporting

confidence: 63%

mentioning

confidence: 99%

¹⁸F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

Nakagawa¹,

Yamada²,

Suzuki³

2008

J Nucl Med

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“…On the other hand, Tohma et al [33] stated that Glut1 expression had a weak correlation with FDG accumulation. Chung et al [34] investigated Glut1 expression in LNs of non-small cell lung cancer. They showed that the mean percentage of Glut1-positive cells in tumors was significantly higher, and the mean Glut1 staining intensity was significantly greater, in PET-positive than in PET-negative metastatic LNs.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between the Glucose Transporter Type 1 Expression and <sup>18</sup>F-Fluorodeoxyglucose Uptake in Esophageal Squamous Cell Carcinoma

Hiyoshi

Watanabe²,

Imamura³

et al. 2009

Oncology

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Objective: Glucose transporter type 1 (Glut1) has been reported to be present in several types of carcinomas. The aims of this study are to evaluate Glut1 expression in both primary tumors and metastatic lymph nodes (LNs) of esophageal squamous cell carcinoma (ESCC) and to assess the relationship between Glut1 expression and ¹⁸F-fluorodeoxyglucose (FDG) accumulation. Methods: We immunohistochemically examined the expression of Glut1 in 60 surgically resected primary lesions and 95 metastatic LNs of ESCC and classified them into 3 groups. The FDG accumulation was assessed with a positron emission tomography (PET). Results: In the primary tumors, a high Glut1 expression was found to be significantly associated with advanced lesions: depth of tumor (p < 0.01), LN metastasis (p < 0.05) and advanced pathological stage (p < 0.01). The Glut1 expression of the metastatic LNs significantly correlated with that of each primary tumor (p < 0.001). The PET-positive lesions had a larger size and higher Glut1 expression than the PET-negative lesions in both the primary tumors and metastatic LNs. Conclusions: In both the primary tumors and metastatic LNs of ESCC, the Glut1 expression and tumor size correlated with the FDG accumulation and influence the sensitivity of the PET scan.

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“…Similar tumor behavior prediction with 18 F-FDG PET in relation to activity of hexokinase enzyme has also been reported in experimental colon cancer (100). However, other animal studies with implanted human colon cancer cell lines suggest that, compared with hexokinase activity, GLUT1 is the more essential factor for 18 F-FDG accumulation in the colon tumor (101). However, cells in culture can genetically drift and one must be careful about the applicability of results from cell culture or xenograft models to patient tumors.…”

Section: Colon Cancermentioning

confidence: 99%

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

Jadvar

Alavi²,

Gambhir³

2009

J Nucl Med

204

176

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It is hoped that in the not too distant future, noninvasive imagingbased molecular interrogation and characterization of tumors can improve our fundamental understanding of the dynamic biologic behavior of cancer. For example, the new dimension of diagnostic information that is provided by 18 F-FDG PET has led to improved clinical decision making and management changes in a substantial number of patients with cancer. In this context, the aim of this review is to bring together and summarize the current data on the correlation between the underlying molecular biology and the clinical observations of tumor 18 F-FDG accumulation in 3 major human cancers: lung, breast, and colon.Key Words: molecular biology; molecular imaging; oncology; PET; PET/CT; breast cancer; colon cancer; 18 F-FDG; lung cancer Theemergenceoft he central role of PET with 18 F-FDG for the imaging evaluation of patients with cancer is undeniable. The development of hybrid PET/CT systems, regional distribution centers for 18 F-FDG, rapidly accumulating clinical experience, and improved reimbursement have all contributed to this phenomenal success. 18 F-FDG PET has been used for diagnosis, initial staging, restaging, prediction, and monitoring of treatment response, surveillance, and prognostication in a variety of cancers. The new dimension of diagnostic information that is provided by 18 F-FDG PET has also led to improved clinical decision making and management changes in a substantial number of patients (1-3).18 F-FDG PET is a molecular imaging technique that monitors tissue glucose metabolism. It has long been known that most tumors are hypermetabolic, with increased glucose metabolism (Warburg effect). The underlying mechanism and reason for elevated glucose metabolism in cancers is multifactorial and more complex than it may appear at first glance (4). These factors include but are not limited to tumor-related components (e.g., type and histologic differentiation), biochemical and molecular alterations (e.g., glucose metabolic pathway, hypoxia), and nontumor-related constituents (e.g., inflammation) (5-8). The 2 recent excellent reviews by Gillies et al. and Plathow et al. summarized the current understanding of the phenotype of elevated glucose metabolism in cancers (9,10). In simple terms, it was postulated that the relationship between tumor growth and glucose metabolism may be explained in terms of adaptation to hypoxia through upregulation of glucose transporters (GLUTs) and translocation and increased enzymatic activity of hexokinase. However, energy production by glycolysis is relatively inefficient (2 adenosine triphosphates produced per glucose with glycolysis rather than 30 ATPs produced with complete oxidation) and produces a toxic acidic microenvironment (9,10). It has been proposed that the increased extracellular acid production may be the underlying basis for promoting tumor survival and spread in the context of the 6 hallmarks of cancer-self-sufficiency in growth signals, insensitivity to antigrowth signals, evasion of apopt...

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FDG uptake and glucose transporter type 1 expression in lymph nodes of non-small cell lung cancer

Cited by 17 publications

References 15 publications

¹⁸F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

¹⁸F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

The Relationship between the Glucose Transporter Type 1 Expression and <sup>18</sup>F-Fluorodeoxyglucose Uptake in Esophageal Squamous Cell Carcinoma

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

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FDG uptake and glucose transporter type 1 expression in lymph nodes of non-small cell lung cancer

Cited by 17 publications

References 15 publications

18F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

18F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

The Relationship between the Glucose Transporter Type 1 Expression and <sup>18</sup>F-Fluorodeoxyglucose Uptake in Esophageal Squamous Cell Carcinoma

18F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization

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¹⁸F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

¹⁸F-FDG Uptake in Reactive Neck Lymph Nodes of Oral Cancer: Relationship to Lymphoid Follicles

¹⁸F-FDG Uptake in Lung, Breast, and Colon Cancers: Molecular Biology Correlates and Disease Characterization