Lab Med Online.  2022 Jan;12(1):26-32. 10.47429/lmo.2022.12.1.26.

Analytical and Clinical Assessment of Prostate Specific Antigen Using an HISCL-5000 Chemiluminescence Immunoassay

• Han J
• Jekarl DW
• Lee S
• Kim M
• Kim Y

• KMID: 2538580
• DOI: http://doi.org/10.47429/lmo.2022.12.1.26

Abstract

Background
Prostate cancer (PCa) is the leading cause of cancer-related death worldwide. Prostate specific antigen (PSA) is a useful biomarker that can be screened for the diagnosis and prognosis of PCa. We evaluated the analytical performance of the PSA test using an HISCL-5000 immunoassay (Sysmex, Japan).
Methods
The analytical and clinical evaluation of PSA was performed using an HISCL-5000 chemiluminescent enzyme immunoassay. For analyzing the precision, linearity, trueness, limit of detection (LOD), limit of blank (LOB) and for comparing the method with UniCel DxI-800 ACCESS (Beckman Coulter, USA), 510 samples of PSA were collected. Clinical analyses were performed for benign prostate hyperplasia (BPH) and PCa. The area under the receiver operating characteristic curve (AUROC) was used for evaluating the diagnostic potential.
Results
The within-laboratory coefficient of variation (CV) for low- (3.81 ng/mL) and high- (18.19 ng/mL) level PSA was 5.46% and 8.50%, respectively. Linearity was verified from 0.002 to 189.900 ng/mL for PSA. LOB and LOD were 0.007 and 0.020 ng/mL, respectively. Bias between the expected true and measured values was -9.70-11.16%. The regression equation by method comparison was y=-1.0605+0.9223x (R₂=0.99). AUROC values for diagnosis of PCa and BPH compared to non-malignant disease were 0.52 and 0.75, respectively. When compared to healthy subjects, AUROC values were 0.96 and 0.97, respectively.
Conclusions
PSA analysis using an HISCL-5000 immunoassay is reliable and can be used in clinical settings.

Keyword

Prostate specific antigen; Tumor marker; Immunoassay; Evaluation; Prostate cancer

Figure

• 

  Fig. 1 Linearity of the HISCL-5000 immunoassay for PSA. The red line and green lines indicate regression lines with linear and non-linear fit, respectively. Linearity was measured from 0.002 to 189.900 ng/mL.

• 

  Fig. 2 Method comparison for HISCL-5000 immunoassay and UniCel DxI-800 immunoassay for PSA (N=363, R2=0.99). (A) Measured range was from 0.01 to 541.56 ng/mL. The slope (95% confidence interval) was 0.92 (0.91-0.93) for PSA. The intercept (95% confidence interval) was -1.06 (-1.71~-0.40). (B) Bland-Altman plot shows the mean difference and upper and lower limit of 1.96 SD.

• 

  Fig. 3 Comparison of AUROCs in the BPH group with control group of non-malignant disease (A). PCa group with control group of non-malignant disease (B). BPH group with control group of healthy population (C). PCa group with control group of healthy population (D). Abbreviations: BPH, benign prostate hyperplasia; PCa, prostate cancer.

Reference

1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. 2018; Global cancer statistics 2018; GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. DOI: 10.3322/caac.21492. PMID: 30207593.

2. Ilic D, Djulbegovic M, Jung JH, Hwang EC, Zhou Q, CLeves A, et al. 2018; Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis. BMJ. 362:k3519. DOI: 10.1136/bmj.k3519. PMID: 30185521. PMCID: PMC6283370.

3. Lilja H, Ulmert D, Vickers AJ. 2008; Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer. 8:268–78. DOI: 10.1038/nrc2351. PMID: 18337732.

4. Iremashvili V, Solosay MS, Rosenberg DL, Manoharan M. 2012; Clinical and demographic characteristics associated with prostate cancer progression in patients on active surveillance. J Urol. 187:1594–9. DOI: 10.1016/j.juro.2011.12.082. PMID: 22425088.

5. Bañez LL, Hamilton RJ, Partin AW, Vollmer RT, Sun L, Rodriguez C, et al. 2007; Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer. JAMA. 298:2275–80. DOI: 10.1001/jama.298.19.2275. PMID: 18029831.

6. Leibovici D, Spiess PE, Agarwal PK, Tu SM, Pettaway CA, HItzhusen K, et al. 2007; Prostate cancer progression in the presence of undetectable or low serum prostate specific antigen level. Cancer. 109:198–204. DOI: 10.1002/cncr.22372. PMID: 17171704.

7. Pinsky PF, Prorok PC, Kramer BS. 2017; Prostate cancer screening-a perspective on the current state of the evidence. N Engl J Med. 376:1285–9. DOI: 10.1056/NEJMsb1616281. PMID: 28355509.

8. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Zappa M, Nelen V, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet. 2014; 384:2027–35. DOI: 10.1016/S0140-6736(14)60525-0. PMID: 25108889. PMCID: PMC4427906.

9. Hugosson J, Carlsson S, Aus G, Bergdahl S, Khatami A, Lodding P, et al. 2010; Mortality results from the Goteborg randomized population based prostate cancer screening trail. Lancet Oncol. 11:725–32. DOI: 10.1016/S1470-2045(10)70146-7.

10. Oberaigner W, Siebert U, Horninger W, Klocker H, Bektic J, Schäfer G, et al. Prostate specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008. Int J. Public Health. 2012; 57–62. DOI: 10.1007/s00038-011-0266-4. PMID: 21681451. PMCID: PMC3281998.

11. Kitagawa Y, Namiki M. 2015; Prostate specific antigen based population screening for prostate cancer: current status in Japan and future perspective in Asia. Asian J Androl. 17:475–80. DOI: 10.4103/1008-682X.143756. PMID: 25578935. PMCID: PMC4430954.

12. Kakehi Y, Sugimoto M, Taoka R. 2017; Evidence based clinical practice guideline for prostate cancer (summary: Japanese Urological Association, 2016 edition). Int J Urol. 24:648–66. DOI: 10.1111/iju.13380. PMID: 28667698.

13. US Preventive Services Task Force. Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, et al. 2018; Screening for prostate cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 319:1901–13. DOI: 10.1001/jama.2018.3710. PMID: 29801017.

14. Schaefer U, Witt F, Schueller P, Micke O, Willich N. 2000; Prostate-specific antigen (PSA) in the monitoring of prostate cancer after radical prostatectomy and external beam radiation. Anticancer Res. 20:4989–92. PMID: 11326654.

15. Freedland SJ, Sutter ME, Dorey F, Aronson WJ. 2003; Defining the ideal cutpoint for determining PSA recurrence after radical prostatectomy. Prostate-specific antigen. Urology. 61:365–9. DOI: 10.1016/S0090-4295(02)02268-9. PMID: 12597949.

16. Clinical, Laboratory Standard Institute. Evaluation of precision of quantitative measurement procedures; approved guideline, Third edition. CLSI document EP05-A3. Wayes, PA: Clinical and Laboratory Standard Institute;2014.

17. Westgard QC. Desirable Biological Variation Database specifications. https://www.westgard.com/biodatabase1.htm. Last accessed on July 2021.

18. Clinical, Laboratory Standard Institute. Evaluation of the linearity of quantitative measurement procedures: A statistical approach; Approved guideline, CLSI document EP06-A. Wayne, PA: Clinical and Laboratory Standard Institute;2003.

19. Clinical, Laboratory Standard Institute. Evaluation of detection capability for clinical laboratory measurement procedures; Approved guideline, Second edition. CLSI document EP17-A2. Clinical and Laboratory Standard Institute;2012.

20. Clinical, Laboratory Standard Institute. 2014. User verification of precision and estimation of bias; Approved guideline-Third edition. CLSI document EP15-A3. Wayne, PA: Clinical and Laboratory Standards Institute;2014.

21. Clinical, Laboratory Standard Institute. 2013. Measurement procedure comparison and bias estimation using patient samples; Approved guideline, Third edition. CLSI document EP09-A3. Clinical and Laboratory Standard Institute;Wayne PA:

22. Obuchowski NA, Lieber ML, Wians FH Jr. 2004; ROC curves in clinical chemistry: uses, misuses, and possible solutions. Clin Chem. 50:1118–25. DOI: 10.1373/clinchem.2004.031823. PMID: 15142978.

23. Ricós C, Alvarez V, Cava F, García-Lario JV, Hernández A, Jiménez CV, et al. 1999; Current databases on biological variation: pros, cons and progress. Scand J Clin Lab Invest. 59:491–500. DOI: 10.1080/00365519950185229. PMID: 10667686.

24. Kort SA, Martens F, Vanpoucke H, van Duijnhoven HL, Blankenstein MA. 2006; Comparison of 6 automated assay for total and free prostate-specific antigen with special reference to their reactivity toward the WHO 96/670 reference preparation. Clin Chem. 52:1568–74. DOI: 10.1373/clinchem.2006.069039. PMID: 16762996.

25. Zur B, Holdenrieder S, Walgenbach-Brünagel G, Albers E, Stoffel-Wagner B. 2012; Method comparison for determination of the tumor markers AFP, CEA, PSA and free PSA between Immulite 2000 XPI and Dimension Vista 1500. Clin Lab. 58:97–105. PMID: 22372351.

26. Laffin R, Chan DW, Tanasijevic MJ, Fischer GA, Markus W, Miller J, et al. 2001; Hybritech Total and free prostate-specific antigen assays developed for the Beckman Coulter Access automated chemiluminescent immunoassay system: a multicenter evaluation of analytical performacne. Clin Chem. 47:129–32. DOI: 10.1093/clinchem/47.1.129. PMID: 11148190.

27. Park HI, Lee S, Kim Y, Shin DY, Lee C, Han S, et al. 2014; Analytical performance of a new one-step quantitative prostate-specific antigen assay, the FRENDTM PSA Plus. Clin Chem Lab Med. 52:715–23. DOI: 10.1515/cclm-2013-0545. PMID: 24323891.

28. Keukeleire SD, Wauters A, Luyts D, Chandler C, Piqueur M. 2014; Analytical performance of the VITROS immunodiagnostic products total PSA II and free PSA assays. Clin Biochem. 47:1323–5. DOI: 10.1016/j.clinbiochem.2014.06.006. PMID: 24940637.