Assessment of the Activity of Lactate Dehydrogenase, Gamma-glutamyl Transpeptidase and Alkaline Phosphatase in Breast Cancer Patients with and without Lymph Node Metastasis
Abstract
Background: Breast cancer has the highest cancer incidence in women and is one of the leading causes of mortality globally. Lactate dehydrogenase (LDH) and other enzymes are vital metabolic enzymes that are associated with cancer development, invasion, and metastasis.
Aim: The present study aimed to evaluate the LDH, Gamma-glutamyl transpeptidase (GGT) and Alkaline phosphatase (ALP) levels in the circulation of patients of breast cancer in different stages and tried to correlate levels with the disease stage and duration of breast cancer with and without lymph node involvement.
Methods: LDH, GGT, and ALP were analyzed by means of the spectrophotometer, Biosystem device and reagents, serum samples were used for measurement.
Results: GGT and LDH had a significant difference with P.value 0.022 and 0.001 respectively between stages II and III, while ALP didn't show a significant difference.
Conclusion: This data concluded that enzyme markers like serum LDH and GGT could be sensitive, specific and cost effective biomarkers for diagnosing carcinoma of the breast and for monitoring its progression
References
1. American Cancer Society. Cancer Facts & Figures. Atlanta: American Cancer Society; (2014).
2. Hill C, Doyon F. [The frequency of cancer in France in the year 2002, and trends since 1968]. Bull Cancer 2006 Jan;93 (1):7-11.
3. Ma X, Yu H. Global burden of cancer. Yale J Biol Med 2006 Dec;79(3-4):85-94.
4. Sasco AJ. Epidemiology of breast cancer: an environmental disease? APMIS 2001 May;109(5):321-32.
5. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
6. Curado MP, Edwards B, Shin HR. Cancer Incidence in Five Continents Lyon: World Health Organization and International Association of Cancer Registries; 2007Available from http://www.iarc.fr/en/publica-tions/pdfs online/epi/sp160/CI5vol9-A.pdfAccessed April 5, 2013.
7. Beral V, Million Women Study Collaborators Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27.
8. Layde PM, Webster LA, Baughman AL, Wingo PA, Rubin GL, Ory HW. The independent associations of parity, age at first full-term pregnancy, and duration of breastfeeding with the risk of breast cancer. Cancer and Steroid Hormone Study Group. J Clin Epidemiol. 1989;42(10):963-73.
9. Caplan LS, Helzlsouer KJ. Delay in breast cancer: a review of the literature. Public Health Rev (1992-1993) 20:187–214.
10. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144: Cell. 2011 Mar 4;144(5):646-74.
11. Vander Heiden MG, Cantley LC, Thompson CB.Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324: 1029–1033.
12. Thorne JL, Campbell MJ. Nuclear receptors and the Warburg effect in cancer. Int J Cancer. 2015 Oct 1;137(7):1519-27.
13. Hirschhaeuser F, Sattler UGa, Mueller-Kleiser W. Lactate: Lactate: a metabolic key player in cancer. Cancer Res. 2011 Nov 15;71(22):6921-5.
14. Maekawa M, Taniguchi T, Ishikawa J, Sugimura H, Sugano K, Kanno T. Promoter hypermethylation in cancer silences LDHB, eliminating lactate dehydrogenase isoenzymes 1-4. Clin Chem 2003.49: 1518–1520.
15. Drent M, Cobben NA, Henderson RF, Wouters EF, van Dieijen-Visser M Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation. Eur Respir J 1996. 9: 1736–1742.
16. Kemp M, Donovan J, Higham H, Hooper J Biochemical markers of myocardial injury. Br J Anaesth 2004. 93: 63–73.
17. Kato GJ, McGowan V, Machado RF, Little JA, Taylor VIJ, Morris CR, Nichols JS, Wang X, Poljakovic M, Morris SM, Gladwin MT Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006;107: 2279–2285.
18. Balch CM, Soong S, Atkins MB, Buzaid AC, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin, 2004;54: 131–149, quiz 182–184.
19. Barlow LJ, Badalato GM, McKiernan JM Serum tumor markers in the evaluation of male germ cell tumors. Nat Rev Urol, 2010;7: 610–617.
20. Armstrong AJ, George DJ, Halabi S Serum lactate dehydrogenase predicts for an overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J Clin Oncol 2012;30: 3402–3407.
21. Nagle SJ, Woo K, Schuster SJ, Nasta SD, Stadtmauer E, Mick R, Svoboda J, Outcomes of patients with relapsed/refractory diffuse large B-cell lymphoma with the progression of lymphoma after autologous stem cell transplantation in the rituximab era. Am J Hematol 2013;88: 890–894
22. Ferreira LMR, Hebrant A, Dumont JE Metabolic reprogramming of the tumor. Oncogene 2012;31: 3999–4011.
23. Petrelli F, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V, Barni S Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta Oncol 2015;54: 961–970.
24. Kazemi-Shirazi L, Endler G, Winkler S, Schickbauer T, Wagner O, Marsik C. Gamma-glutamyltransferase and long-term survival: is it just the liver? Clin Chem. 2007;53(5):940–6. Epub 2007/03/27.
25. Teschke R, Brand A, Strohmeyer G. Induction of hepatic microsomal gamma-glutamyltransferase activity following chronic alcohol consumption. BiochemBiophys Res Commun. 1977;75:718–724.
26. Whitfield JB. Gamma-glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.
27. Kim DJ, Noh JH, Cho NH, Lee BW, Choi YH, Jung JH, et al. Serum gamma glutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors. Diabet Med. 2005;22(9):1134–40. Epub 2005/08/20.
28. Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 2009;136(2):477–85 e11. Epub 2008/12/23.
29. Fishman WH. Oncotrophoblast gene expression: placental alkaline phosphatase. Adv Cancer Res. 1987;48:1–35.
30. Harris H. The human alkaline phosphatases: what we know and what we don’t know. Clin Chim Acta. 1990;186:133–150.
31. Reichling JJ, Kaplan MM. Clinical use of serum enzymes in liver diseases. Dig Dis Sci. 1988;33:1601–1614.
32. Friedman LS, Martin P, Munoz SJ Liver function tests and the objective evaluation of the patient with liver disease. In: Zakim D, Boyer TD (eds) Hepatology: a textbook of liver disease. WB Saunders, Philadelphia, pp 791–833(1996).
33. McIntyre N, Rosalki S. Biochemical investigations in the management of liver disease. In: McIntyre R (ed) Oxford textbook of clinical hepatology. Oxford University Press, Oxford, 1991;pp 293–309.
34. Jemal A1, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90.
35. Guo Li, Jin Gao, Ya-Lan Tao, Bing-Qing Xu, Zi-Wei Tu, Zhi-Gang Liu,1 Mu-Sheng Zeng, and Yun-Fei Xia. Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma. Chin J Cancer. 2012 Apr; 31(4): 197–206.
36. Singh AK, Pandey A, Tewari M, Kumar R, Sharma A, Singh KA, Pandey HP, Shukla HS. Advanced stage of breast cancer hoist alkaline phosphatase activity: risk factor for females in India. 3 Biotech. 2013 Dec;3(6):517-520.
37. Mishra S, Sharma DC, Sharma P. Studies of biochemical parameters in breast cancer with and without metastasis. Indian J Clin Biochem. 2004 Jan;19(1):71-5.
2. Hill C, Doyon F. [The frequency of cancer in France in the year 2002, and trends since 1968]. Bull Cancer 2006 Jan;93 (1):7-11.
3. Ma X, Yu H. Global burden of cancer. Yale J Biol Med 2006 Dec;79(3-4):85-94.
4. Sasco AJ. Epidemiology of breast cancer: an environmental disease? APMIS 2001 May;109(5):321-32.
5. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
6. Curado MP, Edwards B, Shin HR. Cancer Incidence in Five Continents Lyon: World Health Organization and International Association of Cancer Registries; 2007Available from http://www.iarc.fr/en/publica-tions/pdfs online/epi/sp160/CI5vol9-A.pdfAccessed April 5, 2013.
7. Beral V, Million Women Study Collaborators Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003 Aug 9;362(9382):419-27.
8. Layde PM, Webster LA, Baughman AL, Wingo PA, Rubin GL, Ory HW. The independent associations of parity, age at first full-term pregnancy, and duration of breastfeeding with the risk of breast cancer. Cancer and Steroid Hormone Study Group. J Clin Epidemiol. 1989;42(10):963-73.
9. Caplan LS, Helzlsouer KJ. Delay in breast cancer: a review of the literature. Public Health Rev (1992-1993) 20:187–214.
10. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 144: Cell. 2011 Mar 4;144(5):646-74.
11. Vander Heiden MG, Cantley LC, Thompson CB.Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324: 1029–1033.
12. Thorne JL, Campbell MJ. Nuclear receptors and the Warburg effect in cancer. Int J Cancer. 2015 Oct 1;137(7):1519-27.
13. Hirschhaeuser F, Sattler UGa, Mueller-Kleiser W. Lactate: Lactate: a metabolic key player in cancer. Cancer Res. 2011 Nov 15;71(22):6921-5.
14. Maekawa M, Taniguchi T, Ishikawa J, Sugimura H, Sugano K, Kanno T. Promoter hypermethylation in cancer silences LDHB, eliminating lactate dehydrogenase isoenzymes 1-4. Clin Chem 2003.49: 1518–1520.
15. Drent M, Cobben NA, Henderson RF, Wouters EF, van Dieijen-Visser M Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation. Eur Respir J 1996. 9: 1736–1742.
16. Kemp M, Donovan J, Higham H, Hooper J Biochemical markers of myocardial injury. Br J Anaesth 2004. 93: 63–73.
17. Kato GJ, McGowan V, Machado RF, Little JA, Taylor VIJ, Morris CR, Nichols JS, Wang X, Poljakovic M, Morris SM, Gladwin MT Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood 2006;107: 2279–2285.
18. Balch CM, Soong S, Atkins MB, Buzaid AC, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF An evidence-based staging system for cutaneous melanoma. CA Cancer J Clin, 2004;54: 131–149, quiz 182–184.
19. Barlow LJ, Badalato GM, McKiernan JM Serum tumor markers in the evaluation of male germ cell tumors. Nat Rev Urol, 2010;7: 610–617.
20. Armstrong AJ, George DJ, Halabi S Serum lactate dehydrogenase predicts for an overall survival benefit in patients with metastatic renal cell carcinoma treated with inhibition of mammalian target of rapamycin. J Clin Oncol 2012;30: 3402–3407.
21. Nagle SJ, Woo K, Schuster SJ, Nasta SD, Stadtmauer E, Mick R, Svoboda J, Outcomes of patients with relapsed/refractory diffuse large B-cell lymphoma with the progression of lymphoma after autologous stem cell transplantation in the rituximab era. Am J Hematol 2013;88: 890–894
22. Ferreira LMR, Hebrant A, Dumont JE Metabolic reprogramming of the tumor. Oncogene 2012;31: 3999–4011.
23. Petrelli F, Cabiddu M, Coinu A, Borgonovo K, Ghilardi M, Lonati V, Barni S Prognostic role of lactate dehydrogenase in solid tumors: a systematic review and meta-analysis of 76 studies. Acta Oncol 2015;54: 961–970.
24. Kazemi-Shirazi L, Endler G, Winkler S, Schickbauer T, Wagner O, Marsik C. Gamma-glutamyltransferase and long-term survival: is it just the liver? Clin Chem. 2007;53(5):940–6. Epub 2007/03/27.
25. Teschke R, Brand A, Strohmeyer G. Induction of hepatic microsomal gamma-glutamyltransferase activity following chronic alcohol consumption. BiochemBiophys Res Commun. 1977;75:718–724.
26. Whitfield JB. Gamma-glutamyl transferase. Crit Rev Clin Lab Sci. 2001;38(4):263–355.
27. Kim DJ, Noh JH, Cho NH, Lee BW, Choi YH, Jung JH, et al. Serum gamma glutamyltransferase within its normal concentration range is related to the presence of diabetes and cardiovascular risk factors. Diabet Med. 2005;22(9):1134–40. Epub 2005/08/20.
28. Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 2009;136(2):477–85 e11. Epub 2008/12/23.
29. Fishman WH. Oncotrophoblast gene expression: placental alkaline phosphatase. Adv Cancer Res. 1987;48:1–35.
30. Harris H. The human alkaline phosphatases: what we know and what we don’t know. Clin Chim Acta. 1990;186:133–150.
31. Reichling JJ, Kaplan MM. Clinical use of serum enzymes in liver diseases. Dig Dis Sci. 1988;33:1601–1614.
32. Friedman LS, Martin P, Munoz SJ Liver function tests and the objective evaluation of the patient with liver disease. In: Zakim D, Boyer TD (eds) Hepatology: a textbook of liver disease. WB Saunders, Philadelphia, pp 791–833(1996).
33. McIntyre N, Rosalki S. Biochemical investigations in the management of liver disease. In: McIntyre R (ed) Oxford textbook of clinical hepatology. Oxford University Press, Oxford, 1991;pp 293–309.
34. Jemal A1, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90.
35. Guo Li, Jin Gao, Ya-Lan Tao, Bing-Qing Xu, Zi-Wei Tu, Zhi-Gang Liu,1 Mu-Sheng Zeng, and Yun-Fei Xia. Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma. Chin J Cancer. 2012 Apr; 31(4): 197–206.
36. Singh AK, Pandey A, Tewari M, Kumar R, Sharma A, Singh KA, Pandey HP, Shukla HS. Advanced stage of breast cancer hoist alkaline phosphatase activity: risk factor for females in India. 3 Biotech. 2013 Dec;3(6):517-520.
37. Mishra S, Sharma DC, Sharma P. Studies of biochemical parameters in breast cancer with and without metastasis. Indian J Clin Biochem. 2004 Jan;19(1):71-5.
Published
2019-06-01
How to Cite
ABUBAKR, muzdalifa; A. AHMED, Zahra; A. ABDRABO, AbdElkarim.
Assessment of the Activity of Lactate Dehydrogenase, Gamma-glutamyl Transpeptidase and Alkaline Phosphatase in Breast Cancer Patients with and without Lymph Node Metastasis.
Gezira Journal of Health Sciences, [S.l.], v. 15, n. 1, june 2019.
ISSN 1810-5386. Available at: <http://37.60.236.48/index.php/gjhs/article/view/1346>. Date accessed: 03 june 2026.
Issue
Section
Articles
