What are the influencing factors of tumor marker detection
Currently, there are more than 100 kinds of tumor markers (TM) that have been identified, and the results of these TM tests can have a direct impact on patients. In practice, there are many factors affecting TM detection, involving all aspects of pre-analysis, analysis and post-analysis. Here is my knowledge of what factors influence tumor marker testing, welcome to read.
A pre-analytical influencing factors
1, the impact of clinical diagnostic and therapeutic measures on the TM
After prostate massage, prostate puncture, catheterization and proctoscopy, prostate-specific antigen (PSA) and prostate acid phosphatase (PAP) in the blood can be elevated. Certain drugs can affect TM concentrations, such as anti-androgen therapy for prostate cancer can inhibit PSA production; antitumor drugs such as mitomycin and cisplatin can lead to pseudo-elevation of PSA; and some cytotoxic drugs (e.g., 5-fluorouracil) can cause a temporary elevation of carcinoembryonic antigen (CEA) when they are used to treat tumors.
2. Impact of abnormalities in liver and kidney function
Abnormalities in liver function, poor biliary excretion, and biliary stagnation can result in increased concentrations of CEA, alkaline phosphatase (ALP), glutamyl transferase (GGT), and cytokines. Cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC), and ?2 microglobulin (?2-MG) may be elevated in renal dysfunction.
3. The influence of biological factors
PSA increases with age; CA199, CA153, CEA, etc. can be elevated in the elderly. Some women have elevated CA125 and CA199 during menstruation. AFP and CA125 are elevated during pregnancy. CEA is elevated in some chronic smokers.
4, specimen collection and preservation of the impact
Due to the presence of neuron-specific enolase (NSE) in red blood cells and platelets, hemolysis of specimens can increase the concentration of NSE in the blood. Usually blood specimens should be centrifuged in time after collection, stored in a refrigerator at 4 ℃, and measured within 24h; serum that can not be measured within 24h should be stored in a refrigerator at -20 ℃; specimens subject to long-term storage should be placed in a refrigerator at -70 ℃ to save, and should be prevented from repeated freezing and thawing. Enzymes and hormones TM is not stable, easy to degrade, should be measured in a timely manner or separation of serum cryopreservation. In addition, the procoagulant in the test tube has interference with some TM; respiratory secretions, saliva and sweat and other contaminated specimens, can make SCC, CA199 and CEA elevated.
Two factors affecting the analysis
1, the determination of the method and reagents
TM determination methods are radioimmunoassay (RIA), enzyme-linked immunoassay (ELISA) and chemiluminescent immunoassay (CLIA) and so on. Manual methods, due to the addition of samples, washing, incubation, standard curve production and other operational steps, is less reproducible, human error is greater. Automated instrumentation, repeatability is good, human error is small, but different manufacturers, different kits have differences in the determination, the reason is that the use of monoclonal antibodies against the antigen of different sites. Sometimes the same antibody is used, but different results may be obtained due to antigen heterogeneity or the influence of matrix. The main cause of errors in analysis is the lack of standardization of the assay, including the lack of uniform antigen components, calibrators and reference methods. Therefore, it is important to try to use the same method, the same instrument and the same manufacturer's kit for the assay.
2. ? The hook effect?
If the concentration of antigen in the sample to be measured is too high, there will be a high concentration of post-banding phenomenon (? Hook effect?)
3, the impact of cross-contamination
In the determination of high-concentration specimens, cross-contamination becomes a potential problem leading to false positives. Especially in the high concentration of specimens immediately after a specimen, if there is a high result, should be reviewed for cross-contamination.
4. Impact of heterophilic antibodies on test results
Most TM assays often use a pair of murine monoclonal antibodies to react with tumor antigens, such as patients who have used murine monoclonal antibodies due to scintigraphic imaging or treatment, the body will produce human anti-mouse antibodies (HAMA), and HAMA in serum can play a role in the "murine species". HAMA in serum can act as a "bridge" between the "mouse species" and the "monoclonal antibody". HAMA in the serum can act as a "bridge" between the "breeder monoclonal antibodies". HAMA in serum can act as a "bridge" between "species-rat monoclonal antibodies", leading to the false impression of increased TM concentration in the absence of antigen. Special attention should be paid to the issue of heterophilic antibodies in people with a history of close contact with animals to avoid false positives that could lead to medical disputes.
5. The effect of antigen and antibody reaction on TM measurement
Antigen-antibody reaction refers to the specific binding reaction between the antigen and the corresponding antibody, which is affected by the nature of the antigen and antibody, activity, potency, reaction ratio, and the environment (e.g., electrolyte, pH, and temperature), etc.
Antigen-antibody reaction refers to the reaction between the antigen and the corresponding antibody, and the reaction ratio of the antigen and antibody.
Three post-analytical influencing factors
1, the reference value range of TM
Different specimen types such as blood, urine, pleural and abdominal fluids, etc., there must be different. Reference values. Different regions, populations, methods, reagents and equipment should establish their own laboratory reference value range. However, most of the reference values currently used in clinical practice are data reported in foreign literature, and there are few domestic reference ranges of their own, which should be explained to the clinic for reference when diagnosing and analyzing the disease.
2. Changes in basic TM measurements
The TM level of each individual is unknown and fluctuates greatly. When monitoring changes in TM levels in patients at various stages before, during, and after treatment, it is best to make a graph of changes in TM levels and use the level of TM after treatment as a special ? reference level? which is of great value in determining efficacy and monitoring relapse.
3, and clinical exchanges and communication
Due to the TM determination of clinical diagnosis and treatment of the specificity, it is necessary to strengthen the exchanges and communication with the clinic, when the change of the TM detection methods and reagents, the clinic must be notified, so as not to affect the results of the judgment.
In conclusion, there are many factors affecting TM assay, and there is still a lot of work to be done to achieve standardization and normalization of the assay as well as the comparability of results among laboratories. However, a comprehensive understanding and mastery of the characteristics of TM, the rational and scientific use of TM, the strict implementation of operating procedures, and the avoidance of pre-analytical, analytical and post-analytical factors on the test results will certainly make TM test play a more important role in the diagnosis and prevention of tumors.
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