World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Review

Volume 14, Number 1, February 2023, pages 4-14

Carcinoembryonic Antigen, Carbohydrate Antigen 19-9, Cancer Antigen 125, Prostate-Specific Antigen and Other Cancer Markers: A Primer on Commonly Used Cancer Markers

**Table 1.** List of Markers, Reference Levels and Their Associated Cancers
Serial no.	Marker	Associated cancers	Reference level	Reference
CEA: carcinoembryonic antigen; CA 19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein; CA-125: cancer antigen 125; CA 27-29: cancer antigen 27-29; PSA: prostate-specific antigen; B-hCG: beta-human chorionic gonadotropin; Tg: thyroglobulin; LDH: lactate dehydrogenase; 5-HIAA: 5-hydroxyindoleacetic acid; β2M: beta-2 microglobulin; NETs: neuroendocrine tumors.
1	CEA	Colorectal cancer, pancreatic cancer, gastric cancer, hepatobiliary cancer, lung cancer	< 2.5 ng/mL in nonsmokers; < 5 ng/mL in smokers	[2]
2	CA 19-9	Pancreatic ductal adenocarcinoma, gastric cancer, colorectal cancer, lung cancer, thyroid cancer	37 U/mL	[3]
3	AFP	Hepatocellular carcinoma, non-seminomatous germ cell tumors (NSGCTs), gastric cancer, pancreatobiliary cancers	< 20 ng/dL	[4]
4	CA-125	Ovarian cancer, endometrial cancer, breast cancer, gastric cancer	< 35 U/mL	[5]
5	CA 27-29	Breast cancer, colon cancer, lung cancer, pancreatic cancer, ovarian cancer	< 38 U/mL	[6]
6	PSA	Prostate cancer	Aged based: 40 - 49 years: < 2.5 ng/mL; 50 - 59 years: < 3.5 ng/mL; 60 - 69 years: < 4.5 ng/mL; 70 - 79 years < 6.5 ng/mL	[7]
7	B-hCG	Non-seminomatous germ cell tumors, gestational trophoblastic tumors, neuroendocrine cancers, prostate cancer, lung cancer, gastrointestinal tract cancers, cancers of cervix, uterus and vulva	< 5 - 10 IU/mL in men	[8]
8	Tg	Thyroid cancer	1.40 - 29.2 ng/mL males; 1.50 - 38.5 ng/mL females	[9]
9	Calcitonin	Medullary thyroid cancer, neuroendocrine tumors, small cell lung cancer, prostate cancer	< 10 ng/mL	[10]
10	LDH	Testicular germ cell cancers, lung cancer, liver cancer, lymphomas, leukemias	140 - 280 U/L	[11]
11	5-HIAA	Neuroendocrine tumors (particularly small intestinal NETs and metastatic lung NETs)	2 - 8 mg/24 h	[12]
12	β2M	Multiple myeloma, chronic lymphocytic leukemia, lymphomas	< 2 mg/L	[13]

Table 1. List of Markers, Reference Levels and Their Associated Cancers

Serial no.

Marker

Associated cancers

Reference level

Reference

CEA: carcinoembryonic antigen; CA 19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein; CA-125: cancer antigen 125; CA 27-29: cancer antigen 27-29; PSA: prostate-specific antigen; B-hCG: beta-human chorionic gonadotropin; Tg: thyroglobulin; LDH: lactate dehydrogenase; 5-HIAA: 5-hydroxyindoleacetic acid; β2M: beta-2 microglobulin; NETs: neuroendocrine tumors.

CEA

Colorectal cancer, pancreatic cancer, gastric cancer, hepatobiliary cancer, lung cancer

< 2.5 ng/mL in nonsmokers; < 5 ng/mL in smokers

[2]

CA 19-9

Pancreatic ductal adenocarcinoma, gastric cancer, colorectal cancer, lung cancer, thyroid cancer

37 U/mL

[3]

AFP

Hepatocellular carcinoma, non-seminomatous germ cell tumors (NSGCTs), gastric cancer, pancreatobiliary cancers

< 20 ng/dL

[4]

CA-125

Ovarian cancer, endometrial cancer, breast cancer, gastric cancer

< 35 U/mL

[5]

CA 27-29

Breast cancer, colon cancer, lung cancer, pancreatic cancer, ovarian cancer

< 38 U/mL

[6]

PSA

Prostate cancer

Aged based: 40 - 49 years: < 2.5 ng/mL; 50 - 59 years: < 3.5 ng/mL; 60 - 69 years: < 4.5 ng/mL; 70 - 79 years < 6.5 ng/mL

[7]

B-hCG

Non-seminomatous germ cell tumors, gestational trophoblastic tumors, neuroendocrine cancers, prostate cancer, lung cancer, gastrointestinal tract cancers, cancers of cervix, uterus and vulva

< 5 - 10 IU/mL in men

[8]

Thyroid cancer

1.40 - 29.2 ng/mL males; 1.50 - 38.5 ng/mL females

[9]

Calcitonin

Medullary thyroid cancer, neuroendocrine tumors, small cell lung cancer, prostate cancer

< 10 ng/mL

[10]

LDH

Testicular germ cell cancers, lung cancer, liver cancer, lymphomas, leukemias

140 - 280 U/L

[11]

5-HIAA

Neuroendocrine tumors (particularly small intestinal NETs and metastatic lung NETs)

2 - 8 mg/24 h

[12]

β2M

Multiple myeloma, chronic lymphocytic leukemia, lymphomas

< 2 mg/L

[13]

**Table 2.** Serum Markers by Cancer Type, Advantages and Disadvantages
Cancer	Agent	Advantages	Disadvantages
CEA: carcinoembryonic antigen; CA 19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein; CA-125: cancer antigen 125; CA 27-29: cancer antigen 27-29; PSA: prostate-specific antigen; B-hCG: beta-human chorionic gonadotropin; LDH: lactate dehydrogenase; 5-HIAA: 5-hydroxyindoleacetic acid; β2M: beta-2 microglobulin; NETs: neuroendocrine tumors.
Colon cancer	CEA	Marker of choice for monitoring disease activity and for metastatic disease	Poor sensitivity, diverse prevalence of CEA in various nonmalignant conditions
Pancreatic ductal adenocarcinoma	CA 19-9	Monitoring treatment response; Postoperative decrease strongly correlates with improved survival	Not useful in patients with Lewis null phenotype; Not a useful screening marker
Hepatocellular carcinoma	AFP	Independent prognostic factor; Useful for post-treatment monitoring	Suboptimal sensitivity, use in screening is controversial; No use in staging or treatment protocols
Epithelial ovarian cancer	CA-125	Perioperative levels predict successful debulking surgery; Can be used for monitoring treatment response	Low levels in patients with stage I disease hinder early diagnosis
Breast cancer	CA 27-29	Early detection of asymptomatic recurrence	Poor positive predictive value in early stage of disease; Multiple benign disorders increase levels
Prostate cancer	PSA	Useful marker in monitoring for recurrence and metastasis free survival; Prognostic marker	Falsely elevated in benign conditions. Increased screening does not translate to improved overall survival
Non-seminomatous germ cell tumors	B-hCG	Useful in assessing tumor burden, risk stratification and treatment regimen based on degree of marker elevation; prognostic marker	False positive rates seen in tumor lysis, marijuana use and multiple other malignancies
	AFP	Useful in assessing tumor burden, risk stratification and treatment regimen based on degree of marker elevation, prognostic marker	Present in variety of malignant and nonmalignant conditions
	LDH	Useful in assessing tumor burden, risk stratification and treatment regimen based on degree of marker elevation, prognostic marker	Degree of elevation highly nonspecific and may be caused by variety of benign and malignant conditions
Thyroid cancer	Thyroglobulin	Useful in monitoring recurrent and metastatic disease, response to therapy, prognostic marker	Limited screening utility due to association with benign conditions
Medullary thyroid cancer	Calcitonin	Degree of elevation correlates with degree of tumor burden and metastasis, important for postoperative monitoring and evaluation of metastasis	Not available in US, poor positive predictive value due to low prevalence of disease
Neuroendocrine tumors	5-HIAA	Useful in evaluation of carcinoid heart disease, serves as a prognostic factor	Not effective screening marker for all NETs. Levels affected by wide range of foods and medications
Multiple myeloma	β2M	Useful in staging multiple myeloma, prognostic factor, correlates with disease stage and tumor burden	Not specific for multiple myeloma, may be seen in other malignancies and benign conditions

Table 2. Serum Markers by Cancer Type, Advantages and Disadvantages

Cancer

Agent

Advantages

Disadvantages

CEA: carcinoembryonic antigen; CA 19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein; CA-125: cancer antigen 125; CA 27-29: cancer antigen 27-29; PSA: prostate-specific antigen; B-hCG: beta-human chorionic gonadotropin; LDH: lactate dehydrogenase; 5-HIAA: 5-hydroxyindoleacetic acid; β2M: beta-2 microglobulin; NETs: neuroendocrine tumors.

Colon cancer

CEA

Marker of choice for monitoring disease activity and for metastatic disease

Poor sensitivity, diverse prevalence of CEA in various nonmalignant conditions

Pancreatic ductal adenocarcinoma

CA 19-9

Monitoring treatment response; Postoperative decrease strongly correlates with improved survival

Not useful in patients with Lewis null phenotype; Not a useful screening marker

Hepatocellular carcinoma

AFP

Independent prognostic factor; Useful for post-treatment monitoring

Suboptimal sensitivity, use in screening is controversial; No use in staging or treatment protocols

Epithelial ovarian cancer

CA-125

Perioperative levels predict successful debulking surgery; Can be used for monitoring treatment response

Low levels in patients with stage I disease hinder early diagnosis

Breast cancer

CA 27-29

Early detection of asymptomatic recurrence

Poor positive predictive value in early stage of disease; Multiple benign disorders increase levels

Prostate cancer

PSA

Useful marker in monitoring for recurrence and metastasis free survival; Prognostic marker

Falsely elevated in benign conditions. Increased screening does not translate to improved overall survival

Non-seminomatous germ cell tumors

B-hCG

Useful in assessing tumor burden, risk stratification and treatment regimen based on degree of marker elevation; prognostic marker

False positive rates seen in tumor lysis, marijuana use and multiple other malignancies

AFP

Useful in assessing tumor burden, risk stratification and treatment regimen based on degree of marker elevation, prognostic marker

Present in variety of malignant and nonmalignant conditions

LDH

Useful in assessing tumor burden, risk stratification and treatment regimen based on degree of marker elevation, prognostic marker

Degree of elevation highly nonspecific and may be caused by variety of benign and malignant conditions

Thyroid cancer

Thyroglobulin

Useful in monitoring recurrent and metastatic disease, response to therapy, prognostic marker

Limited screening utility due to association with benign conditions

Medullary thyroid cancer

Calcitonin

Degree of elevation correlates with degree of tumor burden and metastasis, important for postoperative monitoring and evaluation of metastasis

Not available in US, poor positive predictive value due to low prevalence of disease

Neuroendocrine tumors

5-HIAA

Useful in evaluation of carcinoid heart disease, serves as a prognostic factor

Not effective screening marker for all NETs. Levels affected by wide range of foods and medications

Multiple myeloma

β2M

Useful in staging multiple myeloma, prognostic factor, correlates with disease stage and tumor burden

Not specific for multiple myeloma, may be seen in other malignancies and benign conditions

**Table 3.** Half-Lives of Serum Tumor Markers
Serial no.	Tumor marker	Half-life	Reference
CEA: carcinoembryonic antigen; CA 19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein; CA-125: cancer antigen 125; PSA: prostate-specific antigen; B-hCG: beta-human chorionic gonadotropin; LDH: lactate dehydrogenase; 5-HIAA: 5-hydroxyindoleacetic acid; β2M: beta-2 microglobulin.
1	CEA	3 - 5 days	[2]
2	CA 19-9	4 - 8 days	[3]
3	AFP	5 - 7 days	[4]
4	CA-125	5 days	[5]
5	PSA	1.83 h	[7]
6	B-hCG	24 - 36 h	[8]
7	Thyroglobulin	14 h	[9]
8	Calcitonin	30 h	[10]
9	LDH	24 h	[11]
10	5-HIAA	1.3 h	[12]
11	β2M	2.5 h	[13]

Table 3. Half-Lives of Serum Tumor Markers

Serial no.

Tumor marker

Half-life

Reference

CEA: carcinoembryonic antigen; CA 19-9: carbohydrate antigen 19-9; AFP: alpha-fetoprotein; CA-125: cancer antigen 125; PSA: prostate-specific antigen; B-hCG: beta-human chorionic gonadotropin; LDH: lactate dehydrogenase; 5-HIAA: 5-hydroxyindoleacetic acid; β2M: beta-2 microglobulin.

CEA

3 - 5 days

[2]

CA 19-9

4 - 8 days

[3]

AFP

5 - 7 days

[4]

CA-125

5 days

[5]

PSA

1.83 h

[7]

B-hCG

24 - 36 h

[8]

Thyroglobulin

14 h

[9]

Calcitonin

30 h

[10]

LDH

24 h

[11]

5-HIAA

1.3 h

[12]

β2M

2.5 h

[13]