Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 12/2014

01-11-2014 | Thoracic Oncology

Prognostic Impact of Clinicopathological Features and Expression of Biomarkers Related to 18F-FDG Uptake in Esophageal Cancer

Authors: L. M. A. Schreurs, MD, PhD, J. K. Smit, MD, PhD, K. Pavlov, MD, B. B. Pultrum, MD, PhD, J. Pruim, MD, PhD, H. Groen, MD, PhD, H. Hollema, MD, PhD, John Th. M. Plukker, MD

Published in: Annals of Surgical Oncology | Issue 12/2014

Login to get access

Abstract

Purpose

To analyze the association between pretreatment 18-F-fluoro-deoxyglucose (FDG) uptake and characteristics of aggressive tumor biology in predicting outcome in esophageal cancer (EC).

Methods

Tumor FDG-uptake was measured by maximum standardized uptake values (SUVmax) in 47 patients undergoing esophagectomy with curative intent. ROC analyses were used to predict an optimal SUVmax cutoff for survival. Expression of hexokinase-II (HK-II), glucose transporter I (GLUT-I), hypoxia inducible factor-1α (HIF-Iα), vascular endothelial growth factor-C (VEGF-C), p53, and proliferative activity (Ki-67) were correlated with SUVmax values and clinicopathological characteristics.

Results

A SUVmax > 3.67 predicted a significantly lower disease-free survival (DFS) and distant recurrence-free survival (p = 0.022 and p = 0.005). High HK-II expression was correlated with reduced SUVmax values (p = 0.002) and was significantly higher in esophageal adenocarcinoma compared with squamous cell carcinoma (p = 0.005). Preoperative high FDG uptake in primary tumors was associated with nodal metastases (pN1; Spearman correlation 0.39, p = 0.01). We found no positive correlation between SUVmax and GLUT-1, HK-1, HIF-Iα 1, VEGF-C, p53, and Ki-67 expression.

Conclusions

High preoperative FDG-uptake strongly predicts poor survival outcome and is associated with lymph node metastases in EC patients. HK-II expression was related to SUVmax and DFS.
Literature
1.
van Westreenen HL, Westerterp M, Bossuyt PM, et al. Systematic review of the staging performance of 18F-fluorodeoxyglucose positron emission tomography in esophageal cancer. J Clin Oncol. 2004;22:3805–12.PubMedCrossRef
2.
van Westreenen HL, Plukker JT, Cobben DC, Verhoogt CJ, Groen H, Jager PL. Prognostic value of the standardized uptake value in esophageal cancer. AJR Am J Roentgenol. 2005;185:436–40.PubMedCrossRef
3.
Schreurs LM, Janssens AC, Groen H, et al. Value of EUS in determining curative resectability in reference to CT and FDG-PET: the optimal sequence in preoperative staging of esophageal cancer? Ann Surg Oncol. 2011. doi:10.​1245/​s10434-011-1738-8 PubMed
4.
Westerterp M, Van Westreenen HL, Sloof GW, Plukker JT, Van Lanschot JJ. Role of positron emission tomography in the (re-)staging of oesophageal cancer. Scand J Gastroenterol. 2006;243:116–22.CrossRef
5.
Zhu WQ, Sun X, Xing L, et al. Oesophageal squamous cell carcinoma: relationship between fluorine-18 fludeoxyglucose positron emission tomography CT maximum standardised uptake value, metabolic tumour volume, and tumour, node and metastasis classification. Br J Radiol. 2012;85:e383–7.PubMedCrossRefPubMedCentral
6.
Suzuki A, Xiao L, Hayashi Y, et al. Prognostic significance of baseline positron emission tomography and importance of clinical complete response in patients with esophageal or gastroesophageal junction cancer treated with definitive chemoradiotherapy. Cancer. 2011;117:4823–33.PubMedCrossRefPubMedCentral
7.
Kobayashi M, Kaida H, Kawahara A, et al. The relationship between GLUT-1 and vascular endothelial growth factor expression and 18F-FDG uptake in esophageal squamous cell cancer patients. Clin Nucl Med. 2012;37:447–52.PubMedCrossRef
8.
Izuishi K, Yamamoto Y, Sano T, et al. Molecular mechanism underlying the detection of colorectal cancer by 18F-2-fluoro-2-deoxy-d-glucose positron emission tomography. J Gastrointest Surg. 2012;16:394–400.PubMedCrossRef
9.
Younes M, Lechago LV, Somoano JR, Mosharaf M, Lechago J. Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers. Cancer Res. 1996;56:1164–7.PubMed
10.
Stein I, Neeman M, Shweiki D, Itin A, Keshet E. Stabilization of vascular endothelial growth factor mRNA by hypoxia and hypoglycemia and coregulation with other ischemia-induced genes. Mol Cell Biol. 1995;15:5363–8.PubMedPubMedCentral
11.
Takala H, Saarnio J, Wiik H, Ohtonen P, Soini Y. HIF-1alpha and VEGF are associated with disease progression in esophageal carcinoma. J Surg Res. 2011;167:41–8.PubMedCrossRef
12.
Katsuta M, Miyashita M, Makino H, et al. Correlation of hypoxia inducible factor-1alpha with lymphatic metastasis via vascular endothelial growth factor-C in human esophageal cancer. Exp Mol Pathol. 2005;78:123–30.PubMedCrossRef
13.
14.
Choi JY, Jang KT, Shim YM, et al. Prognostic significance of vascular endothelial growth factor expression and microvessel density in esophageal squamous cell carcinoma: comparison with positron emission tomography. Ann Surg Oncol. 2006;13:1054–62.PubMedCrossRef
15.
Kleespies A, Guba M, Jauch KW, Bruns CJ. Vascular endothelial growth factor in esophageal cancer. J Surg Oncol. 2004;87:95–104.PubMedCrossRef
16.
Okazawa T, Yoshida T, Shirai Y, et al. Expression of vascular endothelial growth factor C is a prognostic indicator in esophageal cancer. Hepatogastroenterology. 2008;55:1503–8.PubMed
17.
Tzao C, Lee SC, Tung HJ, et al. Expression of hypoxia-inducible factor (HIF)-1alpha and vascular endothelial growth factor (VEGF)-D as outcome predictors in resected esophageal squamous cell carcinoma. Dis Mark. 2008;25:141–8.CrossRef
18.
Ueda S, Tsuda H, Saeki T, et al. Early metabolic response to neoadjuvant letrozole, measured by FDG PET/CT, is correlated with a decrease in the Ki67 labeling index in patients with hormone receptor-positive primary breast cancer: a pilot study. Breast Cancer. 2011;18:299–308.PubMedCrossRef
19.
Han B, Lin S, Yu LJ, Wang RZ, Wang YY. Correlation of (1)(8)F-FDG PET activity with expressions of survivin, Ki67, and CD34 in non-small-cell lung cancer. Nucl Med Commun. 2009;30:831–7.PubMedCrossRef
20.
Motoyama J, Liu J, Mo R, Ding Q, Post M, Hui CC. Essential function of Gli2 and Gli3 in the formation of lung, trachea and oesophagus. Nat Genet. 1998;20:54–7.PubMedCrossRef
21.
Arsic D, Cameron V, Ellmers L, Quan QB, Keenan J, Beasley S. Adriamycin disruption of the Shh-Gli pathway is associated with abnormalities of foregut development. J Pediatr Surg. 2004;39:1747–53.PubMedCrossRef
22.
Shi ST, Yang GY, Wang LD, et al. Role of p53 gene mutations in human esophageal carcinogenesis: results from immunohistochemical and mutation analyses of carcinomas and nearby non-cancerous lesions. Carcinogenesis. 1999;20:591–7.PubMedCrossRef
23.
Groheux D, Giacchetti S, Moretti JL, et al. Correlation of high 18F-FDG uptake to clinical, pathological and biological prognostic factors in breast cancer. Eur J Nucl Med Mol Imaging. 2011;38:426–35.PubMedCrossRef
24.
Chen M, Huang J, Zhu Z, Zhang J, Li K. Systematic review and meta-analysis of tumor biomarkers in predicting prognosis in esophageal cancer. BMC Cancer. 2013;13:539.PubMedCrossRefPubMedCentral
25.
Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56:337–44.PubMedCrossRef
26.
Heagerty PJ, Zheng Y. Survival model predictive accuracy and ROC curves. Biometrics. 2005;61:92–105.PubMedCrossRef
27.
Fukunaga T, Okazumi S, Koide Y, Isono K, Imazeki K. Evaluation of esophageal cancers using fluorine-18-fluorodeoxyglucose PET. J Nucl Med. 1998;39:1002–7.PubMed
28.
Hsu PK, Lin KH, Wang SJ, Huang CS, Wu YC, Hsu WH. Preoperative positron emission tomography/computed tomography predicts advanced lymph node metastasis in esophageal squamous cell carcinoma patients. World J Surg. 2011;35:1321–6.PubMedCrossRef
29.
Hsu WH, Hsu PK, Wang SJ, Lin KH, Huang CS, Hsieh CC, Wu YC. Positron emission tomography-computed tomography in predicting locoregional invasion in esophageal squamous cell carcinoma. Ann Thorac Surg. 2009;87:1564–8.PubMedCrossRef
30.
Haber RS, Rathan A, Weiser KR, et al. GLUT1 glucose transporter expression in colorectal carcinoma: a marker for poor prognosis. Cancer. 1998;83:34–40.PubMedCrossRef
31.
Kawamura T, Kusakabe T, Sugino T, et al. Expression of glucose transporter-1 in human gastric carcinoma: association with tumor aggressiveness, metastasis, and patient survival. Cancer. 2001;92:634–41.PubMedCrossRef
32.
Younes M, Brown RW, Stephenson M, Gondo M, Cagle PT. Overexpression of Glut1 and Glut3 in stage I nonsmall cell lung carcinoma is associated with poor survival. Cancer. 1997;80:1046–51.PubMedCrossRef
33.
Sato-Tadano A, Suzuki T, Amari M, et al. Hexokinase II in breast carcinoma: a potent prognostic factor associated with hypoxia-inducible factor-1alpha and Ki-67. Cancer Sci. 2013;104:1380–8.PubMedCrossRef
34.
Qiu MZ, Han B, Luo HY, et al. Expressions of hypoxia-inducible factor-1alpha and hexokinase-II in gastric adenocarcinoma: the impact on prognosis and correlation to clinicopathologic features. Tumour Biol. 2011;32:159–66.PubMedCrossRef
35.
Ong LC, Jin Y, Song IC, Yu S, Zhang K, Chow PK. 2-[18F]-2-deoxy-d-glucose (FDG) uptake in human tumor cells is related to the expression of GLUT-1 and hexokinase II. Acta Radiol. 2008;49:1145–53.PubMedCrossRef
36.
Hamada K, Tomita Y, Qiu Y, et al. 18F-FDG-PET of musculoskeletal tumors: a correlation with the expression of glucose transporter 1 and hexokinase II. Ann Nucl Med. 2008;22:699–705.PubMedCrossRef
37.
Kato H, Takita J, Miyazaki T, et al. Correlation of 18-F-fluorodeoxyglucose (FDG) accumulation with glucose transporter (Glut-1) expression in esophageal squamous cell carcinoma. Anticancer Res. 2003;23:3263–72.PubMed
38.
Westerterp M, Sloof GW, Hoekstra OS, et al. 18FDG uptake in oesophageal adenocarcinoma: linking biology and outcome. J Cancer Res Clin Oncol. 2008;134:227–36.PubMedCrossRef
39.
Stahl A, Ott K, Weber WA, et al. FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings. Eur J Nucl Med Mol Imaging. 2003;30:288–95.PubMedCrossRef
40.
Takebayashi R, Izuishi K, Yamamoto Y, Kameyama R, Mori H, Masaki T, Suzuki Y. 18F]Fluorodeoxyglucose accumulation as a biological marker of hypoxic status but not glucose transport ability in gastric cancer. J Exp Clin Cancer Res. 2013;32:34.PubMedCrossRefPubMedCentral
41.
Sauter AW, Winterstein S, Spira D, et al. Multifunctional profiling of non-small cell lung cancer using 18F-FDG PET/CT and volume perfusion CT. J Nucl Med. 2012;53:521–9.PubMedCrossRef
Metadata
Title
Prognostic Impact of Clinicopathological Features and Expression of Biomarkers Related to 18F-FDG Uptake in Esophageal Cancer
Authors
L. M. A. Schreurs, MD, PhD
J. K. Smit, MD, PhD
K. Pavlov, MD
B. B. Pultrum, MD, PhD
J. Pruim, MD, PhD
H. Groen, MD, PhD
H. Hollema, MD, PhD
John Th. M. Plukker, MD
Publication date
01-11-2014
Publisher
Springer US
Published in
Annals of Surgical Oncology / Issue 12/2014
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-014-3848-6

Other articles of this Issue 12/2014

Annals of Surgical Oncology 12/2014 Go to the issue

Thoracic Oncology

Single-Institution Retrospective Comparison of Preoperative Versus Definitive Chemoradiotherapy for Adenocarcinoma of the Esophagus

Colorectal Cancer

A Meta-Analysis to Determine the Effect of Primary Tumor Resection for Stage IV Colorectal Cancer with Unresectable Metastases on Patient Survival

Gastrointestinal Oncology

Laparoscopic Narrow-Band Imaging for the Diagnosis of Peritoneal Metastasis in Gastric Cancer

Healthcare Policy and Outcomes

Choosing a Cancer Surgeon: Analyzing Factors in Patient Decision Making Using a Best–Worst Scaling Methodology

Pancreatic Tumors

Preoperative Characteristics of Patients with Presumed Pancreatic Cancer but Ultimately Benign Disease: A Multicenter Series of 344 Pancreatoduodenectomies

Breast Oncology

Breast Radiotherapy (RT) Using Tangential Fields (TgF): A Prospective Evaluation of the Dose Distribution in the Sentinel Lymph Node (SLN) Area as Determined Intraoperatively by Clip Placement