Korean J Lab Med.  2008 Jun;28(3):179-184. 10.3343/kjlm.2008.28.3.179.

Establishment of Reference Intervals of Tumor Markers in Korean Adults

• Woo HY
• Kim YJ
• Park H

• KMID: 854863
• DOI: http://doi.org/10.3343/kjlm.2008.28.3.179

Abstract

BACKGROUND
The sensitivity and specificity of tumor markers for detecting cancer could be significantly changed by the reference intervals of tumor markers. We established reference intervals of tumor markers in Korean adults and evaluated its importance, since the reference intervals recommended by the manufacturers were determined in the Caucasian population and have sometimes been adopted without verification.
METHODS
We established the reference intervals of alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen (CA)125, carbohydrate antigen (CA)19-9, total prostate specific antigen (TPSA), cytokeratin fragment (Cyfra)21-1, and neuron specific enolase (NSE) according to the CLSI guideline in a maximum number of 1,364 healthy adults aged 20-60 yrs who visited a health promotion center from January to February 2007.
RESULTS
Reference intervals of all tumor markers except for AFP were not in agreement with those recommended by the manufacturers. Reference intervals of CEA, TPSA, CA19-9, CA125, and Cyfra21-1 were age dependent. The mean reference values of NSE, CA125, and CEA were statistically different according to gender (11.72 vs 10.78 ng/mL), menopause status (18.89 vs 12.62 U/mL), and smoking status (2.60 vs 2.12 vs 1.80 ng/mL for smokers, past smokers, and non-smokers, respectively),respectively.
CONCLUSIONS
With the verification and establishment of reference intervals of tumor markers in a Korean local population, we found the reference intervals significantly different by either age, gender, smoking or menopause status.

Keyword

Tumor marker; Reference interval; AFP; CEA; CA19-9; CA125; TPSA; Cyfra21-1; NSE

MeSH Terms

Adult
Age Factors
Carcinoembryonic Antigen/analysis
Female
Humans
Korea
Male
Menopause
Middle Aged
Phosphopyruvate Hydratase/analysis
Prostate-Specific Antigen/analysis
Questionnaires
Reagent Kits, Diagnostic
Reference Values
Sex Factors
Smoking
Tumor Markers, Biological/*standards
alpha-Fetoproteins/analysis

Reference

1.Bates S. Clinical application of serum tumor markers. Ann Intern Med. 1991. 115:623–38.

2.Sturgeon C. Practice guidelines for tumor marker use in the clinic. Clin Chem. 2002. 48:1151–9.

3.Sturgeon C., Hammond E., Ch'ng SL., Soletormos G., Hayes DF. National academy of clinical biochemistry: draft guidelines on quality requirements for the use of tumor markers. http://www.aacc.org/AACC/members/nacb/IMPG/OnlineGuide/DraftGuidelines/TumorMarkers/. Accessed 1st February. 2008.

4.Lee MK., Park YK., Park AJ. Reevaluation of the reference range of prostate-specific antigen in Korean men. J Clin Pathol & Quality Control. 2001. 23:221–5. (이미경, 박윤경, 박애자. 한국인에서의혈청 PSA 참고범위의재평가. 임상병리와정도관리 2001;23: 221-5).

5.Semjonow A., Brandt B., Oberpeninning F., Roth S., Hertle L. Discordance of assay methods creates pitfalls for the interpretation of prostate-specific antigen values. Prostate Suppl. 1996. 7:3–16.

6.Sturgeon CM., Seth J. Why do immunoassays for tumour markers give differing results? –a view from the UK national external quality assessment schemes. Eur J Clin Chem Clin Biochem. 1996. 34:755–9.

7.How to define and determine reference intervals in the clinical laboratory; approved guideline- second edition (CLSI document C28-A). Wayne, PA: CLSI;2000.

8.Kim JY., Seong CS., Jeong HS., Seung SL. Clinical efficacy of various tumor markers in medical screening. Korean J Med. 2001. 60:148–55. (김지연, 심성춘, 정현식, 이승세. 건강검진수진자에서종양표지자측정의임상적효율성. 대한내과학회지 2001;60: 148-55.).

9.Kim JE., Lee KT., Lee JK., Paik SW., Rhee JC., Choi KW. Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol. 2004. 19:182–6.

10.Sturgeon CM. Tumor markers in the laboratory: closing the guideline-practice gap. Clin Biochem. 2001. 34:353–9.

11.Ito K., Yamamoto T., Kubota Y., Suzuki K., Fukabori Y., Kurokawa K, et al. Usefulness of age-specific reference range of prostate-specific antigen for Japanese men older than 60 years in mass screening for prostate cancer. Urology. 2000. 56:278–82.

12.Stevenes D., Mackay IR. Increased carcinoembryonic antigen in heavy cigarette smokers. Lancet. 1973. 2:1238–9.

13.Engaras B., Hafstrom L., Kewenter J., Nilsson O., Wedel H. Standard serum concentrations and normal fluctuations of CEA, CA 50 and CA 242 during twelve months in men and women aged 60-64 years without malignant disease. Eur J Surg. 1999. 165:110–6.

14.Meriadec de Byans B., Ducimetiere P., Richard JL., Salard JL., Henry R. Variations in carcinoembryonic antigen levels correlated with tobacco consumption in normal subject. Biomedicine. 1976. 25:197–8.

15.DeAntoni EP., Crawford ED., Oesterling JE., Ross CA., Berger ER., McLeod DG, et al. Age- and race-specific reference ranges for prostate-specific antigen from a large community-based study. Urology. 1996. 48:234–9.

16.Bon GG., Kenemans P., Verstraeten R., van Kamp GJ., Hilgers J. Serum tumor marker immunoassays in gynecologic oncology: establishment of reference values. Am J Obstet Gynecol. 1996. 174:107–14.

17.Costey M., Mora J., Leon X., Lopez M., Orus C., Verges J, et al. CEA and Cyfra 21.1 study pre-treatment in 252 patients with head and neck carcinomas. Acta Otorrinolaringol Esp. 2004. 55:338–42.

18.Deng YF., Chen P., Lin YZ., Le JZ., Wu XL., Yu MQ, et al. Analytical and clinical evaluation of CYFRA 21-1 by electrochemiluminescent immunoassay in head and neck squamous cell carcinoma. J Laryngol Otol. 2003. 117:190–4.

19.Kao CH., Hsieh JF., Ho YJ., Tsai SC., Lee JK. Cytokeratin fragment 19 (CYFRA 21-1) in healthy smokers. Anticancer Res. 1999. 19:4545–6.

20.Henderson RJ., Eastham JA., Culkin DJ., Kattan MW., Whatley T., Mata J, et al. Prostate-specific antigen (PSA) and PSA density: racial differences in men without prostate cancer. J Natl Cancer Inst. 1997. 89:134–8.

21.Behbehani AI., Mathew A., Farghaly M., van Dalen A. Reference levels of the tumor markers carcinoembryonic antigen, the carbohydrate antigens 19-9 and 72-4, and cytokeratin fragment 19 using the Elecsys Relecsys 1010 analyzer in a normal population in Kuwait. The importance of the determination of local reference levels. Int J Biol Markers. 2002. 17:67–70.

22.Soletormos G., Schioler V., Nielsen D., Skovsgaard T., Dombernowsky P. Interpretation of results for tumor markers on the basis of analytical imprecision and biological variation. Clin Chem. 1993. 39:2077–83.