Correct understanding of the clinical significance of tumor markers

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Malignant tumor is a serious threat to the safety and health of the people. In April 29, 2008, the Ministry of Health announced the third ca


Malignant tumor is a serious threat to the safety and health of the people. In April 29, 2008, the Ministry of Health announced the third cause of death investigation in China: cancer is the second cause of death in China, accounting for about 22.3% of the total number of deaths, but in urban areas, cancer mortality has become the first cause of death. Compared with the two causes of death in 70s and 90s of last century, the death rate of cancer has increased by 83.1% and 25.5% respectively. The number of cancer deaths per year in China is 1 million 500 thousand; the number of new cancer patients is about 2 million; the annual cost of cancer patients is about $100 billion, accounting for about 20% of the total health expenditure. Early diagnosis is the key to cure cancer. At present, the clinical application of a variety of special examination in order to improve the early diagnostic rate of the tumor, including X-ray, ultrasonography, CT, magnetic resonance imaging, endoscopy, etc.. These methods can be used in the diagnosis of tumors from different angles and sides. The appearance of tumor markers (tumor marker, TM) makes people have great hope for the early diagnosis of tumors. The detection of tumor markers is of great significance in the diagnosis and prognosis of tumor. With the development of molecular biology and the human genome project, more and more specific tumor markers have been discovered and applied, which provides a new way for early diagnosis of tumors. However, many research reports exaggerated the role of tumor markers, misleading some clinical workers and the masses to understand the significance of tumor marker detection, correct evaluation of the significance of tumor markers in clinical work and reasonable application of great significance.

Tumor markers

Tumor marker refers to the occurrence and proliferation of tumor produced by the tumor cells themselves, or by the body of tumor cells generated by the reaction of the tumor, reflect the existence and growth of a class of substances, including proteins, hormones, enzymes, polyamines (isozyme) and cancer gene product etc.. The diagnosis was found in 1846 Bence - Jones protein was used in multiple myeloma has become the first reported tumor markers found in 1963 AFP, 1965 found CEA, human immune and tumor immune diagnosis of 1978 Herberman NCI will be held in the United States for the first time put forward the tumor marker concept after tumor markers widely used in clinical. At present, there are more than 100 kinds of tumor markers with clinical significance. Ideal tumor markers should have the following characteristics: (1) high sensitivity; specificity; (2) (3) to locate the tumor; (4) and the severity of the disease, tumor size or stage; (5) to monitoring the effects of cancer treatment; (6) monitoring tumor recurrence; (7) to predict the prognosis of tumor. But so far, there is no " ideal " tumor markers. Because of the complexity of the tumor gene, there is no single type of tumor, so it is difficult to find the ideal tumor marker of " ".

Two. The role of tumor markers in tumor screening

Whether the tumor is found early cancer screening program evaluation is effective for the detection method should be simple, safe and reliable and no damage to the body, and has high sensitivity and specificity, the detection result is accurate and reliable, very few false positive and false negative. The following principles should be considered in the use of tumor markers: (1) the tumor markers are highly sensitive to the early detection of tumors. (2) the sensitivity, specificity and repeatability of the method were good. (3) screening costs are economical and reasonable. (4) tumor markers increased abnormally, but there were no signs or symptoms. But in fact, the specificity and sensitivity of a tumor marker could not reach l00%, so that the tumor markers were limited to the census. In colon cancer screening as an example, the incidence rate of 37/10 million, as of a group of people with carcinoembryonic antigen (CEA) for colorectal cancer screening, the false positive rate as high as 4998, and the detection of colon cancer patients, only 26 people, which can cause a lot of waste of medical resources and examination fees. Therefore, this type of tumor markers are generally not suitable for asymptomatic population census. It has been confirmed that, in addition to AFP help to improve screening for liver cancer high-risk population of hepatocellular carcinoma early diagnosis, early diagnosis of PSA, F-PSA and their ratio is helpful to prostate cancer and other tumor markers is of great significance for the early diagnosis of cancer, its clinical value is mainly reflected in the analysis of efficacy, predicting the prognosis and recurrence transfer and etc..

Three. To improve the correct understanding of tumor markers negative

Although the sensitivity can reach more than 80% of many tumor markers, but due to the heterogeneity of the tumor, a considerable number of patients without expression of tumor markers in tumor pathogenesis, resulting in many patients and doctors blindly optimistic in the face of the tumor marker negative results, do further examination, lost a good results the time for the treatment of tumors, causing a lot of regret. For example, such as AFP for the early diagnosis of primary liver cancer with considerable significance of tumor markers, the positive rate of only 79% ~ 90%, (AFP diagnosis of primary liver cancer with a positive threshold of 400ng/ml). In other words, there are 10% to 30% of patients with primary liver cancer, AFP is normal or only slightly elevated. Therefore, in clinical work, the doctor should also be vigilant in the face of tumor markers of negative reports, according to the specific condition of patients a careful history, careful physical examination, combined with the corresponding auxiliary examination, to avoid unnecessary misdiagnosis.

Four. To evaluate the abnormal results of tumor markers

The vast majority of tumor markers in malignant tumor and benign tumor, inflammation, and even some normal tissues at the same time, no 100% specific tumor markers, tumor markers increased therefore is not caused by tumor. For example, viral hepatitis and liver cirrhosis patients and pregnant women with AFP may increase, CA19-9 value of obstructive jaundice or rheumatism patients can be higher than normal times, prostatic hypertrophy, prostatitis can have PSA moderately elevated, endometriosis can have CA125 moderately elevated, even long-term smokers will have mild CEA increased. Therefore, the diagnosis of tumor can not rely solely on the detection of tumor markers. A slight increase in the number of tumor markers or the results of each examination did not change significantly when the clinical significance is not large, only the continued rise of the dynamic significance. The examination found that one or several tumor markers increased should be vigilant, need further by B-ultrasound, CT, MR, or PET/CT as the most advanced endoscopic examination means, when necessary by pathological examination to confirm the diagnosis.

The change of tumor markers is very important to evaluate the therapeutic effect and prognosis. Such as after surgery for tumor markers increased by reduced to normal, indicating that the surgical success; no postoperative or slightly decreased, then increased again, suggesting that there may be residual tumor surgery; postoperative decline over time and significantly increased tumor recurrence or metastasis. This suggests that often early in a few months before the onset of clinical symptoms. The elevation of tumor markers can be used to predict the prognosis of patients with tumor, and it can be used as a guide for the adjustment of treatment plan. Tumor markers after treatment matter decreased after treatment the treatment is effective; tumor markers continue to rise, should replace the treatment plan, if the replacement of tumor markers after treatment were increased, often indicates recurrence or metastasis. Another point to note is the clinician, determination of tumor markers concentration immediately after surgery or chemotherapy and radiotherapy, there may be a transient increase, which is due to tumor necrosis, the detection time is right after 6 weeks of treatment.

Five. Rational use of tumor markers

Multiple tumor markers combined detection can improve the sensitivity of diagnosis. The tumor is the result of repeated cloning of a single variant cell, which is a process of multi-step and multi gene carcinogenesis. The biological characteristics of tumor cells with complexity and polymorphism, each tumor entity has different biological characteristics of cells, cell surface receptors, antigen epitope, expression of gene products, growth rate, invasive, metastasis, chemotherapy and radiotherapy on the sensitivity are likely to be far from. These cells may be different in the synthesis, expression and release of tumor markers. Therefore, the same kind of tumor may contain one or more tumor markers, and different tissues of different tumors or different types of tumors can have common tumor markers and different tumor markers. In order to improve the positive rate of tumor markers detection, the use of some specific tumor markers for joint detection can improve the application value of tumor markers.

The combined application of tumor markers should also pay attention to a problem, that is the rationality of the combined application of tumor markers as part of high correlation between things, such as the correlation between CA199 and CA50 can reach 95% ~ 98%, 95% ~ 98% of the subjects such as CA199 normal, CA50 normal, abnormal CA199 then, CA50 is also abnormal, then you can use some of the higher sensitivity of tumor markers, such as CA724. For example, CA242 is less affected by jaundice, and has high value in the differential diagnosis of benign and malignant diseases of biliary tract and pancreas.

Six. Regular follow-up of tumor markers

Many clinicians do not understand the principles of follow-up of tumor markers, and recommendations for follow-up of patients with tumor markers are also different. The recommendations of the expert committee of the Chinese Academy of Medical Sciences on the tumor markers of the Chinese Medical Association are: after the end of the treatment of malignant tumors, should be based on the condition of the treatment of elevated tumor markers for regular follow-up monitoring. Different tumor markers have different half lives, so the monitoring time and period are also different. Most experts at home and abroad suggest that after 6 weeks of treatment for the first time to determine; every year in March, once every year in; 3~5 every six months; 5~7 once a year. If there was a significant increase in follow-up, it should be measured again in January, 2 times in a row. This prediction is often earlier than clinical symptoms and signs, and help clinical treatment in a timely manner.

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