Advertisement

Annals of Surgical Oncology

, Volume 21, Issue 12, pp 3751–3757 | Cite as

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

  • L. M. A. Schreurs
  • J. K. Smit
  • K. Pavlov
  • B. B. Pultrum
  • J. Pruim
  • H. Groen
  • H. Hollema
  • John Th. M. PlukkerEmail author
Thoracic Oncology

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.

Keywords

18F-FDG-PET Biomarkers Standardized uptake values Prognosis Esophageal cancer 

Notes

Disclosure

No commercial, financial or personal conflicts of interest.

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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 PubMedGoogle Scholar
  4. 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.CrossRefGoogle Scholar
  5. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. 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.PubMedPubMedCentralGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 13.
    Bradbury PA, Zhai R, Ma C, et al. Vascular endothelial growth factor polymorphisms and esophageal cancer prognosis. Clin Cancer Res. 2009;15:4680–5.PubMedCrossRefPubMedCentralGoogle Scholar
  14. 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.PubMedCrossRefGoogle Scholar
  15. 15.
    Kleespies A, Guba M, Jauch KW, Bruns CJ. Vascular endothelial growth factor in esophageal cancer. J Surg Oncol. 2004;87:95–104.PubMedCrossRefGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.PubMedCrossRefGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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.PubMedCrossRefGoogle Scholar
  23. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Heagerty PJ, Lumley T, Pepe MS. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics. 2000;56:337–44.PubMedCrossRefGoogle Scholar
  26. 26.
    Heagerty PJ, Zheng Y. Survival model predictive accuracy and ROC curves. Biometrics. 2005;61:92–105.PubMedCrossRefGoogle Scholar
  27. 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.PubMedGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • L. M. A. Schreurs
    • 1
    • 3
  • J. K. Smit
    • 1
  • K. Pavlov
    • 2
  • B. B. Pultrum
    • 1
  • J. Pruim
    • 4
  • H. Groen
    • 5
  • H. Hollema
    • 6
  • John Th. M. Plukker
    • 1
    Email author
  1. 1.Department of Surgical Oncology/Gastrointestinal SurgeryUniversity of Groningen/University Medical Center GroningenGroningenThe Netherlands
  2. 2.Department of Gastroenterology and HepatologyUniversity of Groningen/University Medical Center GroningenGroningenThe Netherlands
  3. 3.Department of SurgeryMedical Spectrum TwenteEnschedeThe Netherlands
  4. 4.Department of Nuclear Medicine and Molecular BiologyUniversity of Groningen/University Medical Center GroningenGroningenThe Netherlands
  5. 5.Department of EpidemiologyUniversity of Groningen/University Medical Center GroningenGroningenThe Netherlands
  6. 6.Department of PathologyUniversity of Groningen/University Medical Center GroningenGroningenThe Netherlands

Personalised recommendations