Skip to main content

Advertisement

Log in

Correlation Analysis and Prognostic Impact of 18F-FDG PET and Excision Repair Cross-Complementation Group 1 (ERCC-1) Expression in Non-Small Cell Lung Cancer

  • Original Article
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to determine the relationship between [18]-2-fluoro-2-deoxy-D-glucose (FDG) uptake and excision repair cross-complementation group 1 (ERCC-1) expression and to evaluate the prognostic effect of these two factors in resectable non-small cell lung cancer (NSCLC) patients.

Methods

We retrospectively reviewed 212 patients with resectable NSCLC who underwent FDG positron emission tomography/computed tomography (PET/CT) scan for cancer staging and ERCC-1 expression analysis between January 2008 to December 2011. All patients were then followed-up for survival analysis. Semiquantitative evaluation of ERCC-1 was performed with the H-scoring system and was correlated with maximum standardized uptake value (SUVmax) of NSCLC. Univariate and multivariate analyses were performed to evaluate for FDG uptake and ERCC-1 expression predicting overall survival.

Results

In 212 patients (139 male, median age 68 ± 9.11), 112 patients had ERCC-positive tumors and 100 patients had ERCC-negative tumors. There was no significant difference in SUVmax between ERCC-1-positive tumors (8.02 ± 5.40) and ERCC-1-negative tumors (7.57 ± 6.56, p = 0.584). All patients were followed-up for a median of 40.5 months (95 % confidence interval [CI], 38.5–42.2 months). Univariate analysis and multivariate analysis for all patients showed that both ERCC-1 expression (hazard ratio [HR], 2.78; 95 % CI, 1.20–6.47) and FDG uptake (HR, 4.50; 95 % CI, 2.07–9.77) independently predicted overall survival.

Conclusions

We have found no statistical correlation between FDG uptake and ERCC-1 expression in NSCLC. However, both higher FDG uptake and positive ERCC-1 expression are independent predictive markers of prognosis, suggesting that both should be obtained during patient workup.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Chansky K, Sculier JP, Crowley JJ, Giroux D, Van Meerbeeck J, Goldstraw P, et al. The international association for the study of lung cancer staging project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol. 2009;4(7):792–801. doi:10.1097/JTO.0b013e3181a7716e.

    Article  PubMed  Google Scholar 

  2. Heon S, Johnson BE. Adjuvant chemotherapy for surgically resected non-small cell lung cancer. J Thorac Cardiovasc Surg. 2012;144(3):S39–42. doi:10.1016/j.jtcvs.2012.03.039.

    Article  CAS  PubMed  Google Scholar 

  3. Lord RV, Brabender J, Gandara D, Alberola V, Camps C, Domine M, et al. Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res. 2002;8(7):2286–91.

    CAS  PubMed  Google Scholar 

  4. Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006;24(29):4731–7. doi:10.1200/JCO.2006.06.1101.

    Article  CAS  PubMed  Google Scholar 

  5. Ceppi P, Volante M, Novello S, Rapa I, Danenberg KD, Danenberg PV, et al. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann Oncol. 2006;17(12):1818–25. doi:10.1093/annonc/mdl300.

    Article  CAS  PubMed  Google Scholar 

  6. Olaussen KA, Dunant A, Fouret P, Brambilla E, Andre F, Haddad V, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006;355(10):983–91. doi:10.1056/NEJMoa060570.

    Article  CAS  PubMed  Google Scholar 

  7. Cobo M, Isla D, Massuti B, Montes A, Sanchez JM, Provencio M, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol. 2007;25(19):2747–54. doi:10.1200/JCO.2006.09.7915.

    Article  CAS  PubMed  Google Scholar 

  8. Simon G, Sharma A, Li X, Hazelton T, Walsh F, Williams C, et al. Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2007;25(19):2741–6. doi:10.1200/JCO.2006.08.2099.

    Article  CAS  PubMed  Google Scholar 

  9. Reynolds C, Obasaju C, Schell MJ, Li X, Zheng Z, Boulware D, et al. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J Clin Oncol. 2009;27(34):5808–15. doi:10.1200/JCO.2009.21.9766.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. van Vuuren AJ, Appeldoorn E, Odijk H, Yasui A, Jaspers NG, Bootsma D, et al. Evidence for a repair enzyme complex involving ERCC1 and complementing activities of ERCC4, ERCC11 and xeroderma pigmentosum group F. EMBO J. 1993;12(9):3693–701.

    PubMed Central  PubMed  Google Scholar 

  11. Bellmunt J, Paz-Ares L, Cuello M, Cecere FL, Albiol S, Guillem V, et al. Gene expression of ERCC1 as a novel prognostic marker in advanced bladder cancer patients receiving cisplatin-based chemotherapy. Ann Oncol. 2007;18(3):522–8. doi:10.1093/annonc/mdl435.

    Article  CAS  PubMed  Google Scholar 

  12. Kwon HC, Roh MS, Oh SY, Kim SH, Kim MC, Kim JS, et al. Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer. Ann Oncol. 2007;18(3):504–9. doi:10.1093/annonc/mdl430.

    Article  PubMed  Google Scholar 

  13. Hsu DS, Lan HY, Huang CH, Tai SK, Chang SY, Tsai TL, et al. Regulation of excision repair cross-complementation group 1 by Snail contributes to cisplatin resistance in head and neck cancer. Clin Cancer Res. 2010;16(18):4561–71. doi:10.1158/1078-0432.CCR-10-0593.

    Article  CAS  PubMed  Google Scholar 

  14. Vilmar A, Sorensen JB. Excision repair cross-complementation group 1 (ERCC1) in platinum-based treatment of non-small cell lung cancer with special emphasis on carboplatin: a review of current literature. Lung Cancer. 2009;64(2):131–9. doi:10.1016/j.lungcan.2008.08.006.

    Article  PubMed  Google Scholar 

  15. Smirnov S, Pashkevich A, Liundysheva V, Babenko A, Smolyakova R. Heterogeneity of excision repair cross–complementation group 1 gene expression in non–small–cell lung cancer patients. Mol Clin Oncol. 2014. doi:10.3892/mco.2014.415.

  16. Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res. 2005;11(8):2785–808. doi:10.1158/1078-0432.CCR-04-2626.

    Article  CAS  PubMed  Google Scholar 

  17. Lee-Kwon W, Park D, Bernier M. Involvement of the Ras/extracellular signal-regulated kinase signalling pathway in the regulation of ERCC-1 mRNA levels by insulin. Biochem J. 1998;331(Pt 2):591–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Kaira K, Endo M, Shukuya T, Kenmotsu H, Naito T, Ono A, et al. (1)(8)F-FDG uptake on PET could be a predictive marker of excision repair cross-complementation group 1 (ERCC1) expression in patients with thoracic neoplasms? Neoplasma. 2012;59(3):257–63. doi:10.4149/neo_2012_033.

    Article  CAS  PubMed  Google Scholar 

  19. Duan XY, Wang W, Wang JS, Shang J, Gao JG, Guo YM. Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer. BMC Cancer. 2013;13:546. doi:10.1186/1471-2407-13-546.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Strauss GM, Kwiatkowski DJ, Harpole DH, Lynch TJ, Skarin AT, Sugarbaker DJ. Molecular and pathologic markers in stage I non-small-cell carcinoma of the lung. J Clin Oncol. 1995;13(5):1265–79.

    CAS  PubMed  Google Scholar 

  21. Ota S, Ishii G, Goto K, Kubota K, Kim YH, Kojika M, et al. Immunohistochemical expression of BCRP and ERCC1 in biopsy specimen predicts survival in advanced non-small-cell lung cancer treated with cisplatin-based chemotherapy. Lung Cancer. 2009;64(1):98–104. doi:10.1016/j.lungcan.2008.07.014.

    Article  PubMed  Google Scholar 

  22. Booton R, Ward T, Ashcroft L, Morris J, Heighway J, Thatcher N. ERCC1 mRNA expression is not associated with response and survival after platinum-based chemotherapy regimens in advanced non-small cell lung cancer. J Thorac Oncol. 2007;2(10):902–6. doi:10.1097/JTO.0b013e318155a637.

    Article  PubMed  Google Scholar 

  23. Lee KH, Lee SH, Kim DW, Kang WJ, Chung JK, Im SA, et al. High fluorodeoxyglucose uptake on positron emission tomography in patients with advanced non-small cell lung cancer on platinum-based combination chemotherapy. Clin Cancer Res. 2006;12(14 Pt 1):4232–6. doi:10.1158/1078-0432.CCR-05-2710.

    Article  CAS  PubMed  Google Scholar 

  24. Na II, Byun BH, Kang HJ, Cheon GJ, Koh JS, Kim CH, et al. 18F-fluoro-2-deoxy-glucose uptake predicts clinical outcome in patients with gefitinib-treated non-small cell lung cancer. Clin Cancer Res. 2008;14(7):2036–41. doi:10.1158/1078-0432.CCR-07-4074.

    Article  CAS  PubMed  Google Scholar 

  25. Imamura Y, Azuma K, Kurata S, Hattori S, Sasada T, Kinoshita T, et al. Prognostic value of SUVmax measurements obtained by FDG-PET in patients with non-small cell lung cancer receiving chemotherapy. Lung Cancer. 2011;71(1):49–54. doi:10.1016/j.lungcan.2010.04.004.

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

Yong Hyu Jeong, Choong-kun Lee, Kwanhyeong Jo, Sang Hyun Hwang, Jongtae Cha, Jeong Won Lee, Mijin Yun and Arthur Cho declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000. The institutional review board approval number of this study is 4-2014-0715, and informed consent was waived.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Arthur Cho.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jeong, Y.H., Lee, Ck., Jo, K. et al. Correlation Analysis and Prognostic Impact of 18F-FDG PET and Excision Repair Cross-Complementation Group 1 (ERCC-1) Expression in Non-Small Cell Lung Cancer. Nucl Med Mol Imaging 49, 108–114 (2015). https://doi.org/10.1007/s13139-014-0304-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-014-0304-2

Keywords

Navigation