Skip to main content
Top
Published in: BMC Cancer 1/2013

Open Access 01-12-2013 | Research article

Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer

Authors: Xiao-Yi Duan, Wen Wang, Jian-Sheng Wang, Jin Shang, Jun-Gang Gao, You-Min Guo

Published in: BMC Cancer | Issue 1/2013

Login to get access

Abstract

Background

The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) ( Drugs 72(Suppl 1):28–36, 012.), p53 ( Med Sci Monit 11(6):HY11–HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) ( J Thorac Oncol 8(5):582–586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG–PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUVmax) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG–PET SUVmax in NSCLC.

Methods

FDG–PET SUVmax was calculated in chemotherapy naïve patients with NSCLC (n = 62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUVmax difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUVmax and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUVmax in suggesting chemotherapy resistant tumor markers.

Results

The significant tumor type (P = 0.045), differentiation (P = 0.021), p53 (P = 0.000) or ERCC1 (P = 0.033) positivity dependent differences of SUVmax values were observed. The tumor differentiation is significantly correlated with SUVmax (R = -0.327), tumor size (R = -0.286), grading (R = -0.499), gender (R = 0.286) as well as the expression levels for p53 (R = -0.605) and ERCC1 (R = -0.644). The expression level of p53 is significantly correlated with SUVmax (R = 0.508) and grading (R = 0.321). Furthermore, multiple stepwise regression analysis revealed that p53 expression was the primary predictor for SUVmax. When the cut-off value of SUVmax was set at 5.15 in the ROC curve analysis, the sensitivity and specificity of SUVmax in suggesting p53 positive NSCLC were 79.5% and 47.8%, respectively.

Conclusion

The current study suggests that SUVmax of primary tumor on FDG-PET might be a simple and good non-invasive method for predicting p53-related chemotherapy resistance in NSCLC when we set the cu-off value of SUVmax at 5.15.
Appendix
Available only for authorised users
Literature
1.
go back to reference Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al: Cancer treatment and survivorship statistics, 2012. CA. 2012, 62 (4): 220-241.PubMed Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al: Cancer treatment and survivorship statistics, 2012. CA. 2012, 62 (4): 220-241.PubMed
2.
go back to reference Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA: Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proc. 2008, 83 (5): 584-594.CrossRef Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA: Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proc. 2008, 83 (5): 584-594.CrossRef
3.
go back to reference Yuan K, Qian C, Zheng R: Prognostic significance of immunohistochemical Rac1 expression in survival in early operable non-small cell lung cancer. Med Sci Monit. 2009, 15 (11): BR313-BR319.PubMed Yuan K, Qian C, Zheng R: Prognostic significance of immunohistochemical Rac1 expression in survival in early operable non-small cell lung cancer. Med Sci Monit. 2009, 15 (11): BR313-BR319.PubMed
4.
go back to reference Saisho S, Yasuda K, Maeda A, Yukawa T, Okita R, Hirami Y, Shimizu K, Nakata M: Post-recurrence survival of patients with non-small-cell lung cancer after curative resection with or without induction/adjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 2013, 16 (2): 166-172. 10.1093/icvts/ivs450.CrossRefPubMed Saisho S, Yasuda K, Maeda A, Yukawa T, Okita R, Hirami Y, Shimizu K, Nakata M: Post-recurrence survival of patients with non-small-cell lung cancer after curative resection with or without induction/adjuvant chemotherapy. Interact Cardiovasc Thorac Surg. 2013, 16 (2): 166-172. 10.1093/icvts/ivs450.CrossRefPubMed
5.
go back to reference Booth CM, Shepherd FA, Peng Y, Darling G, Li G, Kong W, Biagi JJ, Mackillop WJ: Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study. Cancer. 2013, 119 (6): 1243-1250. 10.1002/cncr.27823.CrossRefPubMed Booth CM, Shepherd FA, Peng Y, Darling G, Li G, Kong W, Biagi JJ, Mackillop WJ: Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study. Cancer. 2013, 119 (6): 1243-1250. 10.1002/cncr.27823.CrossRefPubMed
6.
go back to reference Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J, International Adjuvant Lung Cancer Trial Collaborative G: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004, 350 (4): 351-360.CrossRefPubMed Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J, International Adjuvant Lung Cancer Trial Collaborative G: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004, 350 (4): 351-360.CrossRefPubMed
7.
go back to reference Alam N, Shepherd FA, Winton T, Graham B, Johnson D, Livingston R, Rigas J, Whitehead M, Ding K, Seymour L: Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer. 2005, 47 (3): 385-394. 10.1016/j.lungcan.2004.08.016.CrossRefPubMed Alam N, Shepherd FA, Winton T, Graham B, Johnson D, Livingston R, Rigas J, Whitehead M, Ding K, Seymour L: Compliance with post-operative adjuvant chemotherapy in non-small cell lung cancer. An analysis of National Cancer Institute of Canada and intergroup trial JBR.10 and a review of the literature. Lung Cancer. 2005, 47 (3): 385-394. 10.1016/j.lungcan.2004.08.016.CrossRefPubMed
8.
go back to reference Stewart DJ, Chiritescu G, Dahrouge S, Banerjee S, Tomiak EM: Chemotherapy dose–response relationships in non-small cell lung cancer and implied resistance mechanisms. Cancer Treat Rev. 2007, 33 (2): 101-137. 10.1016/j.ctrv.2006.12.002.CrossRefPubMed Stewart DJ, Chiritescu G, Dahrouge S, Banerjee S, Tomiak EM: Chemotherapy dose–response relationships in non-small cell lung cancer and implied resistance mechanisms. Cancer Treat Rev. 2007, 33 (2): 101-137. 10.1016/j.ctrv.2006.12.002.CrossRefPubMed
9.
go back to reference d'Amato TA, Landreneau RJ, McKenna RJ, Santos RS, Parker RJ: Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell lung cancer. Ann Thorac Surg. 2006, 81 (2): 440-446. 10.1016/j.athoracsur.2005.08.037. discussion 446–447CrossRefPubMed d'Amato TA, Landreneau RJ, McKenna RJ, Santos RS, Parker RJ: Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell lung cancer. Ann Thorac Surg. 2006, 81 (2): 440-446. 10.1016/j.athoracsur.2005.08.037. discussion 446–447CrossRefPubMed
10.
go back to reference Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Storkel S, et al: EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012, 13 (1): 33-42. 10.1016/S1470-2045(11)70318-7.CrossRefPubMed Pirker R, Pereira JR, von Pawel J, Krzakowski M, Ramlau R, Park K, de Marinis F, Eberhardt WE, Paz-Ares L, Storkel S, et al: EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study. Lancet Oncol. 2012, 13 (1): 33-42. 10.1016/S1470-2045(11)70318-7.CrossRefPubMed
11.
go back to reference D’Amato TA, Landreneau RJ, Ricketts W, Huang W, Parker R, Mechetner E, Yu IR, Luketich JD: Chemotherapy resistance and oncogene expression in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2007, 133 (2): 352-363. 10.1016/j.jtcvs.2006.10.019.CrossRefPubMed D’Amato TA, Landreneau RJ, Ricketts W, Huang W, Parker R, Mechetner E, Yu IR, Luketich JD: Chemotherapy resistance and oncogene expression in non-small cell lung cancer. J Thorac Cardiovasc Surg. 2007, 133 (2): 352-363. 10.1016/j.jtcvs.2006.10.019.CrossRefPubMed
12.
go back to reference Simon GR, Ismail-Khan R, Bepler G: Nuclear excision repair-based personalized therapy for non-small cell lung cancer: from hypothesis to reality. Int J BiochemCell Biol. 2007, 39 (7–8): 1318-1328.CrossRef Simon GR, Ismail-Khan R, Bepler G: Nuclear excision repair-based personalized therapy for non-small cell lung cancer: from hypothesis to reality. Int J BiochemCell Biol. 2007, 39 (7–8): 1318-1328.CrossRef
13.
go back to reference Furukawa H, Ikuma H, Asakura K, Uesaka K: Prognostic importance of standardized uptake value on F-18 fluorodeoxyglucose-positron emission tomography in biliary tract carcinoma. J Surg Oncol. 2009, 100 (6): 494-499. 10.1002/jso.21356.CrossRefPubMed Furukawa H, Ikuma H, Asakura K, Uesaka K: Prognostic importance of standardized uptake value on F-18 fluorodeoxyglucose-positron emission tomography in biliary tract carcinoma. J Surg Oncol. 2009, 100 (6): 494-499. 10.1002/jso.21356.CrossRefPubMed
14.
go back to reference Higashi K, Ueda Y, Sakurai A, Wang XM, Xu L, Murakami M, Seki H, Oguchi M, Taki S, Nambu Y, et al: Correlation of Glut-1 glucose transporter expression with. Eur J Nucl Med. 2000, 27 (12): 1778-1785. 10.1007/s002590000367.CrossRef Higashi K, Ueda Y, Sakurai A, Wang XM, Xu L, Murakami M, Seki H, Oguchi M, Taki S, Nambu Y, et al: Correlation of Glut-1 glucose transporter expression with. Eur J Nucl Med. 2000, 27 (12): 1778-1785. 10.1007/s002590000367.CrossRef
15.
go back to reference Shimizu K, Hirami Y, Saisho S, Yukawa T, Maeda A, Yasuda K, Nakata M: Maximal standardized uptake value on FDG-PET is correlated with cyclooxygenase-2 expression in patients with lung adenocarcinoma. Ann Thorac Surg. 2012, 93 (2): 398-403. 10.1016/j.athoracsur.2011.10.033.CrossRefPubMed Shimizu K, Hirami Y, Saisho S, Yukawa T, Maeda A, Yasuda K, Nakata M: Maximal standardized uptake value on FDG-PET is correlated with cyclooxygenase-2 expression in patients with lung adenocarcinoma. Ann Thorac Surg. 2012, 93 (2): 398-403. 10.1016/j.athoracsur.2011.10.033.CrossRefPubMed
16.
go back to reference Watanabe K, Nomori H, Ohtsuka T, Naruke T, Ebihara A, Orikasa H, Yamazaki K, Uno K, Kobayashi T, Goya T: [F-18]Fluorodeoxyglucose positron emission tomography can predict pathological tumor stage and proliferative activity determined by Ki-67 in clinical stage IA lung adenocarcinomas. Jpn J Clin Oncol. 2006, 36 (7): 403-409. 10.1093/jjco/hyl043.CrossRefPubMed Watanabe K, Nomori H, Ohtsuka T, Naruke T, Ebihara A, Orikasa H, Yamazaki K, Uno K, Kobayashi T, Goya T: [F-18]Fluorodeoxyglucose positron emission tomography can predict pathological tumor stage and proliferative activity determined by Ki-67 in clinical stage IA lung adenocarcinomas. Jpn J Clin Oncol. 2006, 36 (7): 403-409. 10.1093/jjco/hyl043.CrossRefPubMed
17.
go back to reference Kaira K, Oriuchi N, Shimizu K, Ishikita T, Higuchi T, Imai H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T, et al: Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer. Cancer Sci. 2009, 100 (4): 753-758. 10.1111/j.1349-7006.2008.01077.x.CrossRefPubMed Kaira K, Oriuchi N, Shimizu K, Ishikita T, Higuchi T, Imai H, Yanagitani N, Sunaga N, Hisada T, Ishizuka T, et al: Correlation of angiogenesis with 18F-FMT and 18F-FDG uptake in non-small cell lung cancer. Cancer Sci. 2009, 100 (4): 753-758. 10.1111/j.1349-7006.2008.01077.x.CrossRefPubMed
18.
20.
go back to reference Koksal D, Demirag F, Bayiz H, Ozmen O, Tatci E, Berktas B, Aydogdu K, Yekeler E: The correlation of SUVmax with pathological characteristics of primary tumor and the value of Tumor/ Lymph node SUVmax ratio for predicting metastasis to lymph nodes in resected NSCLC patients. J Cardiothorac Surg. 2013, 8: 63-10.1186/1749-8090-8-63.CrossRefPubMedPubMedCentral Koksal D, Demirag F, Bayiz H, Ozmen O, Tatci E, Berktas B, Aydogdu K, Yekeler E: The correlation of SUVmax with pathological characteristics of primary tumor and the value of Tumor/ Lymph node SUVmax ratio for predicting metastasis to lymph nodes in resected NSCLC patients. J Cardiothorac Surg. 2013, 8: 63-10.1186/1749-8090-8-63.CrossRefPubMedPubMedCentral
21.
go back to reference Brabender J, Danenberg KD, Metzger R, Schneider PM, Park J, Salonga D, Holscher AH, Danenberg PV: Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival. Clin Cancer Res. 2001, 7 (7): 1850-1855.PubMed Brabender J, Danenberg KD, Metzger R, Schneider PM, Park J, Salonga D, Holscher AH, Danenberg PV: Epidermal growth factor receptor and HER2-neu mRNA expression in non-small cell lung cancer Is correlated with survival. Clin Cancer Res. 2001, 7 (7): 1850-1855.PubMed
22.
go back to reference Taylor MD, Smith PW, Brix WK, Wick MR, Theodosakis N, Swenson BR, Kozower BD, Jones DR: Correlations between selected tumor markers and fluorodeoxyglucose maximal standardized uptake values in esophageal cancer. Eur J Cardiothorac Surg. 2009, 35 (4): 699-705. 10.1016/j.ejcts.2008.11.029.CrossRefPubMedPubMedCentral Taylor MD, Smith PW, Brix WK, Wick MR, Theodosakis N, Swenson BR, Kozower BD, Jones DR: Correlations between selected tumor markers and fluorodeoxyglucose maximal standardized uptake values in esophageal cancer. Eur J Cardiothorac Surg. 2009, 35 (4): 699-705. 10.1016/j.ejcts.2008.11.029.CrossRefPubMedPubMedCentral
23.
go back to reference Jiang J, Liang X, Zhou X, Huang R, Chu Z, Zhan Q: ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysis. Mol Biol Rep. 2012, 39 (6): 6933-6942. 10.1007/s11033-012-1520-4.CrossRefPubMed Jiang J, Liang X, Zhou X, Huang R, Chu Z, Zhan Q: ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysis. Mol Biol Rep. 2012, 39 (6): 6933-6942. 10.1007/s11033-012-1520-4.CrossRefPubMed
24.
go back to reference Thottassery JV, Zambetti GP, Arimori K, Schuetz EG, Schuetz JD: p53-dependent regulation of MDR1 gene expression causes selective resistance to chemotherapeutic agents. Proc Natl Acad Sci USA. 1997, 94 (20): 11037-11042. 10.1073/pnas.94.20.11037.CrossRefPubMedPubMedCentral Thottassery JV, Zambetti GP, Arimori K, Schuetz EG, Schuetz JD: p53-dependent regulation of MDR1 gene expression causes selective resistance to chemotherapeutic agents. Proc Natl Acad Sci USA. 1997, 94 (20): 11037-11042. 10.1073/pnas.94.20.11037.CrossRefPubMedPubMedCentral
25.
go back to reference Nakamura H, Hirata T, Kitamura H, Nishikawa J: Correlation of the standardized uptake value in FDG-PET with the expression level of cell-cycle-related molecular biomarkers in resected non-small cell lung cancers. Ann Thorac Cardiovasc Surg. 2009, 15 (5): 304-310.PubMed Nakamura H, Hirata T, Kitamura H, Nishikawa J: Correlation of the standardized uptake value in FDG-PET with the expression level of cell-cycle-related molecular biomarkers in resected non-small cell lung cancers. Ann Thorac Cardiovasc Surg. 2009, 15 (5): 304-310.PubMed
Metadata
Title
Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer
Authors
Xiao-Yi Duan
Wen Wang
Jian-Sheng Wang
Jin Shang
Jun-Gang Gao
You-Min Guo
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2013
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-13-546

Other articles of this Issue 1/2013

BMC Cancer 1/2013 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine