Performance evaluation of tumour markers assay on Mindray CL-2000i chemiluminescence immunoassay system

Tumour markers play an important role in the detection and management of cancer. It is critical to evaluate new assay systems for precise measurement of commonly used tumour markers in the clinical setting. The goal of this study is to evaluate the performance of a new Mindray CL-2000i Chemiluminescence Immunoassay System (Mindray CL-2000i system) in comparison with our reference method (Roche COBAS e601 and BCI Dxi 800) using eight tumour markers.

by Minjie Wang, Binbin Han, Xuexiang Li, Jun Qi

Clinical significant of tumour marker measurement
Tumour markers are molecules that indicate the presence of cancer or provide prognosis of a cancer. They are potentially used in screening, helping diagnosis, and predicting the prognosis of malignant diseases [1]. One of the widely studied tumour markers is prostate-specific antigen (PSA) for prostate cancer screening, though PSA is not recommended as a routine screening marker of prostate cancer [2]. α-fetoprotein (AFP) is useful biomarker for the screening of hepatocellular cancer [3], and carbohydrate antigen 125 (CA 125) is related to ovarian cancer, but the value for screening ovarian cancer in asymptomatic women is not yet recognized [4]. Carcinoembryonic antigen (CEA) is widely recommended as surveillance following initial treatment of colorectal cancer [5]. AFP and human chorionic gonadotrophin (HCG) are considered as valuable tumour markers for monitoring non-seminomatous type germ cell tumours of testis [6]. Carbohydrate antigen 15-3 (CA15-3) is the most widely used tumour marker fo 成 r surveillance after diagnosis of breast cancer, and CA19-9 has been recommended for monitoring pancreatic cancer [7]. Elevated ferritin is related to some cancers, such as acute leukemia, Hodgkin’s disease and carcinoma of the lung, colon, liver and prostate [8]. In the present study, we have evaluated the performance of the Mindray CL 2000i system by using eight tumour markers.

Imprecision
Imprecision studies were performed according to the CLSI EP5-A2 guideline (9), and have been evaluated using two samples with low and high concentration. The within-run imprecision was performed by measuring each sample for 20 times. The total imprecision was evaluated by measuring each sample continuously for 20 days with the same lot of reagent, and the samples were assayed in duplicate per run, two runs per day with an interval of at least 2 hours. The imprecision was expressed as coefficient of variation (CV%) in both within runs and total runs. Table 1 shows the result of the within-run and total imprecision of eight tumour markers. The CVs are in a range from 1.38 – 3.59% for within run, and from 2.00 – 5.45% for total imprecision.

Method Comparison
Patient samples from benign diseases to a variety of cancers were freshly collected from the clinical laboratory of our hospital. The samples were preselected based on the result of our reference method to make the concentration evenly distributed within the entire assay range for each analyte. The sample numbers for each analyte are ranged from 251 to 1863 samples. The reference intervals were determined based on the measurement of 70 apparently healthy subjects. The samples are from the leftover of the clinical immunoassays, and the names of the patients were coded to protect the privacy of the subjects. The informed consent was waived by the Ethic committee of the Cancer Hospital, Chinese Academy of Medical Sciences.

The comparison studies were performed using the Mindray CL 2000i and the reference methods in our laboratory [Figure 1]. The slopes for the eight tumour markers range from 0.82 to 1.17 and the intercepts from -23.70 to 5.29. All of the eight markers display very high interassay correlation (r2 > 0.94). FPSA displayed the highest correlation between Mindray CL 2000i system and Roche COBAS e601 system (slope = 1.097; r2 = 0.99) [Figure 1d], while CEA showed the lowest agreement between Mindray CL 2000i system and the Roche COBAS e601 (slope = 1.038; r2 = 0.94) [Figure 1b].

Using the cutoff established based on our reference methods, each tumour marker was evaluated for its analytical concordance between Mindray CL 2000i system and our reference methods (Roche COBAS e601), and the results are listed in Table 2. The analytical agreements are ranged from 97.3% to 100.0%.

Conclusion
In the present study, using eight tumour markers, the performance of Mindray CL-2000i system has been evaluated in comparison with our reference systems. The imprecision was highly acceptable for all the tumour markers tested. The reference intervals provided by the manufacturer are concordant to that from the measurement of normal population in our lab, and the analytical agreement of the Mindray CL-2000i system with our reference methods is very high. The method comparison between the Mindray CL-2000i system and the reference methods evidenced high concordance. The performance parameters of  the Mindray CL-2000i system are well suited for the detection of tumour markers in the clinical settings.

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The authors
Minjie Wang, Binbin Han, Xuexiang Li, Jun Qi*
Department of Clinical Laboratory, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Chaoyang District, Beijing, 100021 China

*Corresponding author
qijun5610@126.com