November 29, 2022

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It means cancer if tumor markers abnormal ?

It means cancer if tumor markers abnormal ?

It means cancer if tumor markers abnormal ? Understand the clinical significance of 10 commonly used tumor markers in one article.

Tumor markers (TM) are produced by tumor cells themselves or abnormally produced and/or increased by the body’s response to tumor cells during the occurrence and proliferation of malignant tumors, reflecting the existence and growth of tumors A class of substances, including proteins, hormones, enzymes (isoenzymes), polyamines and oncogene products, etc., exist in the blood, body fluids, cells or tissues of patients, and can be used in biochemistry, immunology, and molecular biology. The determination is of certain value for the auxiliary diagnosis, differential diagnosis, curative effect observation, recurrence monitoring and prognosis evaluation of tumors.

It means cancer if tumor markers abnormal ?

 

The editor today will give a detailed introduction to alpha-fetoprotein, carcinoembryonic antigen, neuron-specific enolase, squamous cell carcinoma antigen, cytokeratin 19 fragment, gastrin releasing peptide precursor, carbohydrate antigen 125, sugar Top 10 tumor markers including class antigen 15-3, carbohydrate antigen 19-9 and prostate specific antigen (PSA).

 

1. Alpha-fetoprotein (AFP)

AFP is very high during the neonatal period, and drops to 10 µg/L to 20 µg/L by the age of 1 year. The AFP content in adult serum is very low. When liver cells undergo malignant transformation, the content of AFP is significantly increased, which is an important indicator for clinical diagnosis of primary liver cancer.

1). Screening

Serum AFP combined with liver ultrasonography can be used as a screening test for people at high risk of primary liver cancer. High-risk groups are mainly those infected with hepatitis B virus (HBV) and/or hepatitis C virus (HCV), long-term alcoholics, and those with a family history of primary liver cancer. Screening age is male ≥40 years old, female ≥50 Starting from the age of six months, it is advisable to check once every six months.

2). Auxiliary diagnosis

① Serum AFP is the most commonly used tumor marker for clinical auxiliary diagnosis of primary liver cancer (hepatocellular carcinoma for short). For serum AFP ≥400μg/L for more than 1 month, or ≥200μg/L for 2 months, after excluding pregnancy, active liver disease and reproductive embryonic tumors, liver cancer should be highly suspected, and B-ultrasound examination is necessary. Do CT/MRI and biopsy from time to time to confirm the diagnosis. The positive rate of serum AFP in the diagnosis of liver cancer is generally about 70%, and about 30% of patients with liver cancer have a negative AFP test. Therefore, AFP alone cannot be used to diagnose liver cancer.

② Elevated serum AFP can also be seen in germline embryonic tumors, such as testicular non-seminoma, yolk sac tumor, and malignant teratoma. It can also be found in other malignant tumors, such as gastric cancer, colorectal cancer and so on.

③ Serum AFP in patients with acute and chronic hepatitis and liver cirrhosis may increase to varying degrees, mostly between 20 and 200 µg/L, and generally decreases gradually as the condition improves within 2 months.

④ Serum AFP can be seen elevated in women after 3 months of pregnancy, mainly from the fetus. Abnormal increase in serum AFP in pregnant women can be seen in fetal neural tube defects, spina bifida, and anencephaly. AFP can enter the amniotic fluid through the open neural tube and cause its content in the amniotic fluid to increase abnormally. The abnormal decrease in serum AFP in pregnant women indicates that the fetus is at risk of Down’s syndrome. Therefore, monitoring of AFP concentration in maternal serum and amniotic fluid can be used for prenatal diagnosis of fetal neural tube defects and Down’s syndrome.

3). Prognosis evaluation

Serum AFP is an important marker for judging the prognosis of primary liver cancer. A high concentration of serum AFP indicates a poor prognosis.

4). Efficacy and recurrence monitoring

① The determination of serum AFP helps to monitor the response of liver cancer patients to treatment. After liver cancer surgery, the serum AFP concentration drops within the reference range, indicating that the operation is effective; if the serum AFP drops only partly, it indicates that the operation is incomplete or there are metastatic lesions.

② Serum AFP can be used for follow-up and recurrence monitoring after liver cancer surgical resection or liver transplantation in liver cancer patients. It should be tested every 3 months within 2 years after surgery and every 6 months within 3 to 5 years.

 

2. Carcinoembryonic Antigen (CEA)

A complex structure of acid glycoprotein, mainly present in adult cancer tissues and fetal gastrointestinal tissues, is a broad-spectrum tumor marker.

1). Screening

Serum CEA is generally not used for tumor screening in asymptomatic people.

2). Auxiliary diagnosis

① Serum CEA is a relatively broad-spectrum tumor marker. Clinically, it can be used in the auxiliary diagnosis of common tumors such as colon cancer, rectal cancer, lung cancer, breast cancer, esophageal cancer, pancreatic cancer, stomach cancer, metastatic liver cancer, etc. Other malignant tumors such as medullary thyroid carcinoma, cholangiocarcinoma, and urinary system malignancies also have varying degrees of positive rates.

② In pregnancy, colitis, colon polyps, intestinal diverticulitis, pancreatitis, cirrhosis, hepatitis, benign lung diseases and cardiovascular diseases, serum CEA may also increase to varying degrees, but the percentage of positive is low.

3). Prognosis evaluation

Serum CEA level is one of the factors that determine the prognosis of tumors. Serum CEA continues to rise, indicating a poor prognosis.

4). Efficacy and recurrence monitoring

① For patients with elevated CEA before treatment, if surgery, chemotherapy, targeted therapy or immunotherapy is effective, the serum CEA concentration will drop within the reference range; if the serum CEA drops only partly or not after treatment, the treatment effect is not good .

② Serum CEA can be used for follow-up and recurrence monitoring after tumor treatment, generally within 2 years after treatment, preferably every 3 months, and every 6 months within 3 to 5 years.

 

3. Neuron-specific enolase (NSE)

NSE is an acid protease, which is involved in glycolysis and metabolism. The glycolysis of tumor tissues is strengthened, the cell proliferation cycle is accelerated, and the release of NSE in the cells into the blood increases. Tumors originating from neuroendocrine tissues, such as neuroblastoma and small cell lung cancer (SCLC), have elevated serum NSE.

1) Screening

Serum NSE is generally not used for lung cancer screening.

2) Auxiliary diagnosis

① Serum NSE is one of the first choice markers for small cell lung cancer (SCLC). The level of NSE in patients with small cell lung cancer is significantly higher than that of non-small cell lung cancer (NSCLC) such as lung adenocarcinoma, lung squamous cell carcinoma, and large cell lung cancer. It can also be used for the differential diagnosis of small cell lung cancer and non-small cell lung cancer.

② Serum NSE is also a tumor marker of neuroblastoma, which is significantly higher in patients, while it is less frequent in patients with Wilms tumor. Therefore, it can be used for the differential diagnosis of neuroblastoma and Wilms tumor.

③ Elevated serum NSE is also common in neuroendocrine cell tumors, such as pheochromocytoma, medullary thyroid carcinoma, melanoma, islet cell tumor, and retinoblastoma.

④ Serum NSE can also be increased in certain neurological diseases and lung diseases, such as meningitis and pneumonia, but the percentage of positive is low.

3) Prognosis evaluation

Serum NSE is an important prognostic indicator for small cell lung cancer and neuroblastoma. Serum NSE continues to rise, suggesting a poor prognosis.

4) Efficacy and recurrence monitoring

① Serum NSE level can reflect the response to chemotherapy of small cell lung cancer. A temporary increase in NSE (tumor disappearance) can occur 24h to 72h after chemotherapy. The serum NSE level of patients who respond well to chemotherapy will drop rapidly after the end of the first course of treatment. The continuous increase or temporary decrease of the patient’s NSE level indicates that the treatment effect is not good.

② Serum NSE can be used for follow-up and recurrence monitoring of small cell lung cancer. Generally, it should be tested every 3 months within 2 years after treatment, and every 6 months within 3 to 5 years.

 

4. Squamous cell carcinoma antigen (SCC or SCCA)

A tumor marker for detecting squamous cell carcinoma with high specificity but low sensitivity.

1) Screening

Serum SCC is generally not used for screening of cervical squamous cell carcinoma and lung squamous cell carcinoma.

2) Auxiliary diagnosis

① Serum SCC is a tumor marker mainly used to assist in the diagnosis of squamous cell carcinoma. It will increase in the serum of patients with cervical squamous cell carcinoma and lung squamous cell carcinoma, and its concentration will increase with the severity of the disease.

② Serum SCC also has varying degrees of positive rates in other malignant tumors, such as head and neck epithelial cell carcinoma, esophageal cancer, nasopharyngeal carcinoma, and skin cancer.

③ Serum SCC may also increase to varying degrees in certain benign diseases, such as hepatitis, liver cirrhosis, pneumonia, tuberculosis, psoriasis, eczema, renal failure, etc., but the positive percentage is low.

3) Prognosis evaluation

It is generally believed that elevated serum SCC is a risk factor for poor prognosis of cervical squamous cell carcinoma and lung squamous cell carcinoma, but SCC is not recommended for routine use in the prognosis of cervical squamous cell carcinoma and lung squamous cell carcinoma.

4) Efficacy and recurrence monitoring

① Elevated serum SCC is related to cervical squamous cell carcinoma lymph node metastasis and can be used for the formulation of personalized treatment plans for cervical squamous cell carcinoma, but it is not currently used as a routine application.

② Serum SCC concentration is related to the staging of cervical squamous cell carcinoma, tumor size, residual tumor after surgery, tumor recurrence and progression, etc. Therefore, it can be used for the efficacy evaluation, follow-up and recurrence monitoring of cervical cancer.

③ Serum SCC has a certain value in monitoring the efficacy of lung squamous cell carcinoma.

 

5. Cytokeratin 19 fragment (CYFRA 21-1)

It exists in tumor cells of epithelial origin such as lung cancer and esophageal cancer. It is a more sensitive marker for detecting non-small cell lung cancer (NSCLC).

1) Screening

Serum CYFRA 21-1 is generally not used for lung cancer screening.

2) Auxiliary diagnosis

① Serum CYFRA21-1 is one of the first-choice markers for non-small cell lung cancer, especially squamous cell carcinoma, which has auxiliary diagnostic value.

② Serum CYFRA21-1 also has different degrees of positive rates in other malignant tumors, such as bladder cancer, esophageal cancer, nasopharyngeal cancer, ovarian cancer and cervical cancer.

③ Serum CYFRA21-1 may also increase to a certain extent in certain benign diseases, such as hepatitis, liver cirrhosis, pancreatitis, pneumonia, and tuberculosis, but the positive rate is low. Renal failure can lead to an increase in serum CYFRA21-1.

3) Prognosis assessment

Serum CYFRA21-1 is an important prognostic indicator for non-small cell lung cancer. Serum CYFRA21-1 continues to rise, indicating a poor prognosis.

4) Efficacy and recurrence monitoring

① Serum CYFRA21-1 can be used to monitor the efficacy of non-small cell lung cancer. The continuous increase in the concentration of CYFRA21-1 indicates disease progression.

② Serum CYFRA21-1 can be used for follow-up and recurrence monitoring of non-small cell lung cancer. Generally, it should be tested every 3 months within 2 years after treatment, and every 6 months within 3 to 5 years.

 

6. Gastrin releasing peptide precursor (ProGRP)

Stable expression in the blood is a good marker for detecting small cell lung cancer.

1) Screening

Serum ProGRP is generally not used for lung cancer screening.

2) Auxiliary diagnosis

① Serum ProGRP is one of the first-choice markers for small cell lung cancer (SCLC), and it has an auxiliary diagnostic value. It can also be used for the differential diagnosis of small cell lung cancer and non-small cell lung cancer. ProGRP and NSE can increase the positive rate of small cell lung cancer when used in combination.

② Elevated serum ProGRP can also be seen in certain neuroendocrine cell tumors, such as medullary thyroid carcinoma.

③ Serum ProGRP may also be elevated to varying degrees in certain benign diseases, such as urinary system diseases and respiratory system diseases, but the percentage of positive is low. Renal failure can lead to an increase in serum ProGRP.

3) Prognosis assessment

Serum ProGRP is an important prognostic indicator for small cell lung cancer. Serum ProGRP continues to rise, indicating a poor prognosis.

4) Efficacy and recurrence monitoring

① Serum ProGRP can be used to monitor the efficacy of small cell lung cancer. After treatment, the concentration of ProGRP decreases significantly, indicating that the treatment is effective; if the serum ProGRP continues to rise, it indicates poor efficacy.

② Serum ProGRP can be used for follow-up and recurrence monitoring of small cell lung cancer. Generally, it should be tested every 3 months within 2 years after treatment, and every 6 months within 3 to 5 years.

 

7. carbohydrate antigen 125 (CA 125)

Currently, it is commonly used clinically to detect tumor markers for ovarian cancer.

1). Screening and early detection

① Serum CA125 is generally not used for ovarian cancer screening in asymptomatic women.

② For high-risk groups with special genetic mutations or family history of ovarian cancer, serum CA125 combined with vaginal ultrasound can be considered for early detection of ovarian cancer.

2). Auxiliary diagnosis

① Serum CA125 is mainly used for auxiliary diagnosis of ovarian cancer, especially epithelial ovarian cancer. It can also be used as a differential diagnosis index for benign and malignant pelvic tumors in postmenopausal women.

② Serum CA125 also has a certain positive rate in other malignant tumors such as lung cancer, pancreatic cancer, colon cancer and other gynecological tumors.

③ Serum CA125 can also increase to varying degrees in certain benign diseases such as endometriosis, chronic pelvic inflammatory disease, peritonitis, ovarian cysts, pancreatitis, hepatitis, liver cirrhosis and other diseases, but the positive percentage is low. .

 

3. Prognosis assessment

Serum CA125 is one of the factors that determine the prognosis of ovarian cancer. Whether before or after surgery, the continuous increase of serum CA125 indicates a poor prognosis.

 

4. Efficacy and recurrence monitoring

① Continuous detection of serum CA125 can be used to monitor the efficacy of chemotherapy for ovarian cancer. It is usually tested once within 2 weeks before chemotherapy and once during 2 to 4 weeks during chemotherapy. The continuous increase of CA125 during the monitoring period indicates disease progression or poor efficacy.

② For those with elevated serum CA125 before treatment, CA125 can be used for follow-up monitoring after treatment. Generally within 2 years after treatment, it should be tested every 2 to 4 months, and every 3 to 6 months for 3 to 5 years.

 

8. Carbohydrate Antigen 15-3 (CA 15-3)

It has certain value in the auxiliary diagnosis of breast cancer.

1). Screening

Serum CA15-3 is generally not used for breast cancer screening in asymptomatic people.

2). Auxiliary diagnosis

① Serum CA15-3 is an indicator mainly used for the auxiliary diagnosis of breast cancer, but the positive rate of early breast cancer is low, and the positive rate of advanced breast cancer and metastatic breast cancer is higher, ranging from 70% to 80%. The combined detection of CA15-3 and CEA can improve the sensitivity of breast cancer diagnosis.

② Serum CA15-3 also has varying degrees of positive rates in other malignant tumors, such as lung cancer, ovarian cancer, liver cancer, cervical cancer, and colon cancer.

③ Serum CA15-3 may increase to varying degrees in benign diseases such as liver, gastrointestinal tract, lung, breast, ovary, etc., but the positive percentage is low.

3). Prognosis evaluation

Serum CA15-3 is generally not used to judge the prognosis of breast cancer.

4). Efficacy and recurrence monitoring

① Serum CA15-3, together with imaging examination and clinical physical examination, can be used to monitor the treatment response of breast cancer patients. The continuous increase in the concentration of CA15-3 indicates disease progression.

② Serum CA15-3 is not routinely used for breast cancer recurrence and metastasis monitoring. However, those with elevated serum CA15-3 before surgery can be followed up and monitored with CA15-3 after surgery.

 

9. carbohydrate antigen 19-9 (CA 19-9)

Currently, it is commonly used clinically to detect tumor markers of pancreatic cancer.

1). Screening

Serum CA19-9 is generally not used for pancreatic cancer screening.

2). Auxiliary diagnosis

① Serum CA19-9 is often used for auxiliary diagnosis of malignant tumors such as pancreas and biliary tract, but the specificity is not strong enough. The measured value of CA19-9 has nothing to do with the size of pancreatic cancer, but when it is higher than 10000U/mL, there are almost all peripheral metastases.

② Serum CA19-9 also has a certain positive rate in stomach cancer, colon cancer and liver cancer.

③ Serum CA19-9 also has varying degrees of increase in certain benign diseases such as hepatitis, pancreatitis, cholangitis, cholecystitis, liver cirrhosis and other diseases. Pay attention to distinguish it from malignant tumors.

④ 3% to 7% of patients have Lewis antigen-negative blood group structure and do not express CA19-9. Therefore, the CA19-9 test results of these patients are often negative.

3). Prognosis evaluation

Serum CA19-9 combined with clinical data can be used as a comprehensive prognostic indicator of pancreatic cancer.

4.) Efficacy and recurrence monitoring

① Serum CA19-9 together with imaging examinations can be used to monitor the efficacy of pancreatic cancer radiotherapy and chemotherapy. The continuous increase in the concentration of CA19-9 indicates disease progression.

② Serum CA19-9 together with imaging examination can be used for follow-up and recurrence monitoring after pancreatic cancer surgery. In the first year after the operation, follow-up was conducted every 3 months; in the second to third years, the follow-up was conducted every 6 months; after that, every year.

 

10. Prostate Specific Antigen (PSA)

1). Screening

① PSA can be used as an indicator of individualized screening for prostate cancer. The screening is mainly for middle-aged and elderly men, and the screening age can start at 55 years; for high-risk groups of prostate cancer, such as men with a family history of prostate cancer, it can start at 45.

② Screening for prostate cancer should include PSA testing and digital rectal examination.

2). Auxiliary diagnosis

① When the serum PSA concentration is ≥4.0 μg/L, a digital rectal examination (DRE) inspection should be performed.

② If the serum PSA concentration is between 4.0 μ g / L and 10.0 μ g / L in the gray area, if DRE is positive, a prostate biopsy should be performed to confirm the diagnosis. If DRE is negative, the percentage of free PSA (%fPSA) should be tested. If %fPSA<10%, a prostate biopsy should be considered to confirm the diagnosis.

③ If the serum PSA concentration is more than 10.0 μg/L, prostate biopsy should be performed to confirm the diagnosis.

④ The rate of serum PSA is accelerated, increasing at a rate of ≥0.75 μg/(L ·year). After excluding the influencing factors of PSA testing, prostate biopsy should be done. This test is more suitable for young patients with low PSA values.

⑤ The PSA density test can help distinguish between prostate hyperplasia and the elevated PSA caused by prostate cancer. If the PSA density is ≥0.15, after excluding the influencing factors of PSA test, the doctor can guide the doctor to decide whether to perform prostate biopsy.

⑥ Composite PSA (cPSA) testing is not recommended for clinical use, but it can be used for medical research.

3). Efficacy and recurrence monitoring

① Serum PSA determination helps to monitor the response of prostate cancer patients to treatment. After 4 to 6 weeks of prostate cancer eradication surgery, the serum PSA concentration drops below the detection limit, indicating that the operation is effective; if the serum PSA concentration drops only partially, it indicates that the operation is incomplete, there are residual lesions or there are prostate cancer metastases.

② Serum PSA determination has reference value for monitoring the recurrence of prostate cancer.

③ Serum PSA should be tested every 3 months during the first 2 years after the eradication of prostate cancer, every 6 months after 2 years, and once a year after 5 years. During the monitoring, if the serum PSA concentration rises twice in a row, it indicates a biochemical recurrence of prostate cancer.

Principles of combined detection of tumor markers

The same tumor or different types of tumors may have an abnormal concentration of one or several serum tumor markers; the same serum tumor marker may appear in different tumors. In order to improve the diagnostic value of tumor markers and determine which markers are used as follow-up monitoring indicators after treatment, combined detection of tumor markers can be performed, but the combined detection indicators must be scientifically analyzed and strictly screened. Under the above premise, a reasonable selection of several serum tumor markers with high sensitivity and complementary specificity for combined detection.

(source:chinanet, reference only)


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