DOI QR코드

DOI QR Code

Association of High LDH and Low Glucose Levels in Pleural Space with HER2 Expression in Non-Small Cell Lung Cancer

  • Ziaian, Bijan (Department of Surgery, Namazi Hospital) ;
  • Saberi, Ali (Department of Surgery, Namazi Hospital) ;
  • Ghayyoumi, Mohammad Ali (Department of Internal Medicine, School of Medicine, Faghihi Hospital) ;
  • Safaei, Akbar (Department of Pathology, Faghihi Hospital) ;
  • Ghaderi, Abbas (Cancer Proteomics and Biomarkers Lab, Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences) ;
  • Mojtahedi, Zahra (Cancer Proteomics and Biomarkers Lab, Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences)
  • Published : 2014.02.28

Abstract

Background: Evidence shows direct link of HER2 to increased glycolysis and over production of lactate dehydrogenase (LDH). HER2 overexpression, high LDH and low glucose pleural levels are associated with poor prognosis in lung cancer. Here, their relationships were investigated. Materials and Methods: HER2 positivity was studied using immunohistochemistry in non-small cell lung cancer. Glucose and LDH levels were measured using commercial colorimetric kits. Results: Of 42 patients (29 adenocarcinoma and 13 squamous cell carcinoma), 28 (66.7%) were HER2-negative, 14 (33.3%) were HER2- positive, including 9 (21.4%) weakly stained (1+) and 5 (11.9%) moderately stained (2+) samples. The relationship between HER2 and glucose and LDH levels were tested in 20 newly diagnosed lung cancer patients who had simultaneous pleural and serum samples. Pleural and serum LDH levels were increased, and pleural glucose levels were decreased with the scale of HER2 positivity, and that the difference in glucose levels between HER2-negative group and HER2-positive patients scored at 2+ reached statistical significance (p=0.02). This latter group all had pleural glucose levels below 40 mg/dl. Conclusions: For the first time, we showed a significant association between low pleural glucose level and overexpression of HER2 in lung cancer. Further investigations are warranted to disclose the association of HER2 with low pleural glucose levels in other populations, with a larger sample size, in malignant pleural effusions caused by other types of cancer, and finally to assess employment as a screening tool for finding HER2-positive cases of lung cancer.

Keywords

Glucose;HER2;LDH;lung cancer;malignant pleural effusion

References

  1. Zinner RG, Glisson BS, Fossella FV, et al (2004). Trastuzumab in combination with cisplatin and gemcitabine in patients with Her2-overexpressing, untreated, advanced non-small cell lung cancer: report of a phase II trial and findings regarding optimal identification of patients with Her2-overexpressing disease. Lung Cancer, 44, 99-110. https://doi.org/10.1016/j.lungcan.2003.09.026
  2. Panagiotou I, Georgiannos SN, Tsiambas E, et al (2012). Impact of HER2 and PTEN simultaneous deregulation in non-small cell lung carcinoma: correlation with biological behavior. Asian Pac J Cancer Prev, 13, 6311-8. https://doi.org/10.7314/APJCP.2012.13.12.6311
  3. Limthongkul S (1989). The pathogenesis of low pleural fluid glucose in acidotic malignant pleural effusions. J Med Assoc Thai, 72, 492-7.
  4. Masoompour SM, Yarmohammadi H, Rezaianzadeh A, Lankarani KB (2011). Cancer incidence in southern Iran, 1998-2002: results of population-based cancer registry. Cancer Epidemiol, 35, 42-7. https://doi.org/10.1016/j.canep.2011.05.018
  5. Mojtahedi Z, Safaei A, Yousefi Z, Ghaderi A (2011). Immunoproteomics of HER2-positive and HER2-negative breast cancer patients with positive lymph nodes. OMICS, 15, 409-18. https://doi.org/10.1089/omi.2010.0131
  6. Pirker R, Minar W (2010). Chemotherapy of advanced non-small cell lung cancer. Front Radiat Ther Oncol, 42, 157-63.
  7. Sanchez-Armengol A, Rodriguez-Panadero F (1993). Survival and talc pleurodesis in metastatic pleural carcinoma, revisited. Report of 125 cases. Chest, 104, 1482-5. https://doi.org/10.1378/chest.104.5.1482
  8. Xia Q, Zhu Z, Wang J, et al (2012). Expression and association of HER2 with prognosis in early-stage (T1-T2N0M0) nonsmall cell lung cancer. Tumour Biol, 33, 1719-25. https://doi.org/10.1007/s13277-012-0429-9
  9. Zahir ST, Mirtalebi M (2012). Survival of patients with lung cancer, Yazd, Iran. Asian Pac J Cancer Prev, 13, 4387-91. https://doi.org/10.7314/APJCP.2012.13.9.4387
  10. Zhao YH, Zhou M, Liu H, et al (2009). Upregulation of lactate dehydrogenase A by ErbB2 through heat shock factor 1 promotes breast cancer cell glycolysis and growth. Oncogene, 28, 3689-701. https://doi.org/10.1038/onc.2009.229
  11. Ghayumi SMA, Aghasadeghi K, Doroudchi M, Ghaderi A (2006). Determination of soluble HER-2/neu (sher-2/neu) in iranian patients with lung cancer. Iran J Immunol, 3, 61-5.
  12. Bielsa S, Salud A, Martinez M, et al (2008). Prognostic significance of pleural fluid data in patients with malignant effusion. Eur J Intern Med, 19, 334-9. https://doi.org/10.1016/j.ejim.2007.09.014
  13. Bollig-Fischer A, Dewey TG, Ethier SP (2011). Oncogene activation induces metabolic transformation resulting in insulin-independence in human breast cancer cells. PLoS One, 6, 17959. https://doi.org/10.1371/journal.pone.0017959
  14. Ernam D, Atalay F, Hasanoglu HC, Kaplan O (2005). Role of biochemical tests in the diagnosis of exudative pleural effusions. Clin Biochem, 38, 19-23. https://doi.org/10.1016/j.clinbiochem.2004.09.023
  15. Harris LN, Liotcheva V, Broadwater G, et al (2001). Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy. J Clin Oncol, 19, 1698-706. https://doi.org/10.1200/JCO.2001.19.6.1698
  16. Heffner JE, Klein JS (2008). Recent advances in the diagnosis and management of malignant pleural effusions. Mayo Clin Proc, 83, 235-50. https://doi.org/10.1016/S0025-6196(11)60848-3
  17. Hirsch FR, Franklin WA, Bunn PA (2002a). What is the role of HER-2/neu and trastuzumab (Herceptin) in lung cancer? Lung Cancer, 36, 263-4. https://doi.org/10.1016/S0169-5002(02)00011-9
  18. Hirsch FR, Varella-Garcia M, Franklin WA, et al (2002b). Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas. Br J Cancer, 86, 1449-56. https://doi.org/10.1038/sj.bjc.6600286

Cited by

  1. Glucose May Attenuate Isoflurane-Induced Caspase-3 Activation in H4 Human Neuroglioma Cells vol.119, pp.6, 2014, https://doi.org/10.1213/ANE.0000000000000383
  2. Prediction of Lung Cancer Based on Serum Biomarkers by Gene Expression Programming Methods vol.15, pp.21, 2014, https://doi.org/10.7314/APJCP.2014.15.21.9367
  3. Molecular epidemiology of lung cancer in Iran: implications for drug development and cancer prevention vol.63, pp.7, 2018, https://doi.org/10.1038/s10038-018-0450-y