What is a Tumor Marker?

A tumor marker is simply a protein produced by cancer cells or another substance produced by other cells of the body in response to cancer. Though they are NOT always produced and therefore cannot always be used as a viable marker, if they show “out-of-range”, they can be helpful to determine treatment parameters. Positive tumor markers may provide information about a cancer, such as how aggressive it is, whether it can be treated with a targeted therapy, or whether it is responding to current treatment.

The nice thing about tumor markers is that they are measured with a blood test. This gives the patient, if they are present, a non-invasive way to track their care. Many people are hesitant to continue with CT and PET scans due to the radiation exposure of continued use. MRI scans with a contrast dye pose similar risks. A cancer marker test is a simple and inexpensive blood test that you usually MUST REQUEST from your doctor.

Here are some common cancer markers to request:

  1. Alpha Fetoprotein – Normal range: Adults: < 15 ng/ml. more common in Liver cancer and certain types of ovarian and testicular cancers but my show positive in other cancers as well.
  2. CA 15-3 (Cancer Antigen 15-3) – The reference range of serum CA 15-3 is less than 30 U/mL. Cancer antigen 15-3 (CA 15-3) is used to monitor response to breast cancer treatment and disease recurrence.
  3. CA 19-9 (Cancer Antigen 19-9) – Normal results are less than 37 U/mL. A high amount of CA 19-9 is most often caused by pancreatic cancer. But it can also be caused by breast cancer and other types of cancer. And it can also be elevated by infections in your liver, gallbladder, and pancreas.
  4. CA 27-29 (Cancer antigen 27-29) – The reference range of serum CA 27-29 is less than 38 U/mL. This is usually used to predict early recurrence of disease in women with treated carcinoma of the breast.
  5. CA-125 (Cancer Antigen-125) – Normal range: 0 – 35 U/mL.  This is useful for monitoring for ovarian cancer, liver and colon cancers by measuring an antigen to epithelial neoplasms circulating in blood serum. It may also be elevated in liver cirrhosis, uterine fibroids, and endometriosis.
  6. Calcitonin – A normal value is less than 10 pg/mL. Elevated levels of this thyroid hormone occasionally occur with small cell lung cancer.
  7. CEA (Carcinoembryonic Antigen) – A normal result is less than 2.5 nanograms per milliliter for non-smokers and up to 5 nanograms per milliliter for smokers. The most frequent cancer which causes an increased CEA is cancer of the colon and rectum. Others include cancers of the pancreas, stomach, breast, lung, and medullary carcinoma of the thyroid and ovarian cancer. High levels of CEA do not always mean you have cancer. These other conditions can also increase levels: Breast cysts, Chronic obstructive pulmonary disease, infections such as cholecystitis and diverticulitis, inflammatory bowel disease, Liver disease, lung problems, and pancreatitis.
  8. Human Chorionic Gonadotropin (hCG) – A test less than 5 mIU/mL is considered normal. HCG is a nonspecific marker for pancreatic, pituitary, and placental tumors; elevated levels may be present in pancreatic cancer. Of course, it will also be elevated in pregnancy.
  9. LDH (Lactic Dehydrogenase) – Normal levels of LDH in the blood can vary depending on the lab, but usually range between 140 units per liter (U/L) to 280 U/L for adults and tend to be higher for children and teens. The lactate dehydrogenase (LDH) test looks for signs of damage to the body’s tissues and therefore is a common test to help rule out a heart attack. LDH is an enzyme found in almost every cell of your body, including your blood, muscles, brain, kidneys, and pancreas.
  10. Prostate Specific Antigen (PSA) – There is no specific normal or abnormal level of PSA in the blood, and levels may vary over time in the same man. In the past, most doctors considered PSA levels of 4.0 ng/mL and lower as normal. It is best to use this test to monitor care as it rises and falls.

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Here is a more complete list, in alphabetical order, from the National Cancer Institute:

ALK gene rearrangements and over-expression

Cancer types: Non-small cell lung cancer and anaplastic large cell lymphoma
What’s analyzed: Tumor
How used: To help determine treatment and prognosis

Alpha-fetoprotein (AFP)

Cancer types: Liver cancer and germ cell tumors
What’s analyzed: Blood
How used: To help diagnose liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors

B-cell immunoglobulin gene rearrangement

Cancer type: B-cell lymphoma
What’s analyzed: Blood, bone marrow, or tumor tissue
How used: To help in diagnosis, to evaluate effectiveness of treatment, and to check for recurrence

Beta-2-microglobulin (B2M)

Cancer types: Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas
What’s analyzed: Blood, urine, or cerebrospinal fluid
How used: To determine prognosis and follow response to treatment

Beta-human chorionic gonadotropin (Beta-hCG)

Cancer types: Choriocarcinoma and germ cell tumors
What’s analyzed: Urine or blood
How used: To assess stage, prognosis, and response to treatment

Bladder Tumor Antigen (BTA)

Cancer types: Bladder cancer and cancer of the kidney or ureter
What’s analyzed: Urine
How used: As surveillance with cytology and cystoscopy of patients already known to have bladder cancer

BRCA1 and BRCA2 gene mutations

Cancer types: Ovarian and breast cancers
What’s analyzed: Blood and/or tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate. This is NOT technically a tumor marker test.

BCR-ABL fusion gene (Philadelphia chromosome)

Cancer types: Chronic myeloid leukemia, acute lymphoblastic leukemia, and acute myelogenous leukemia
What’s analyzed: Blood or bone marrow
How used: To confirm diagnosis, predict response to targeted therapy, determine whether treatment with a particular type of targeted therapy is appropriate, and monitor disease status

BRAF V600 mutations

Cancer types: Cutaneous melanoma, Erdheim-Chester disease, colorectal cancer, and non-small cell lung cancer
What’s analyzed: Tumor
How used: To select patients who are most likely to benefit from treatment with certain targeted therapies

C-kit/CD117

Cancer types: Gastrointestinal stromal tumor, mucosal melanoma, acute myeloid leukemia, and mast cell disease
What’s analyzed: Tumor, blood, or bone marrow
How used: To help in diagnosing and determining treatment

CA15-3/CA27.29

Cancer type: Breast cancer
What’s analyzed: Blood
How used: To assess whether treatment is working or if the cancer has recurred

CA19-9

Cancer types: Pancreatic, gallbladder, bile duct, and gastric cancers
What’s analyzed: Blood
How used: To assess whether treatment is working

CA-125

Cancer type: Ovarian cancer
What’s analyzed: Blood
How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence

CA 27.29

Cancer type: Breast cancer
What’s analyzed: Blood
How used: To detect metastasis or recurrence

Calcitonin

Cancer type: Medullary thyroid cancer
What’s analyzed: Blood
How used: To aid in diagnosis, check whether treatment is working, and assess recurrence

Carcinoembryonic antigen (CEA)

Cancer types: Colorectal cancer and some other cancers
What’s analyzed: Blood
How used: To keep track of how well cancer treatments are working and check if cancer has come back or spread

CD20

Cancer type: Non-Hodgkin lymphoma
What’s analyzed: Blood
How used: To determine whether treatment with a targeted therapy is appropriate

CD22

Cancer types: Hairy cell leukemia and B-cell neoplasms
What’s analyzed: Blood and bone marrow
How used: To help in diagnosis

CD25

Cancer type: Non-Hodgkin (T-cell) lymphoma
What’s analyzed: Blood
How used: To determine whether treatment with a targeted therapy is appropriate

CD30

Cancer types: Mycosis fungoides and peripheral T-cell lymphoma
What’s analyzed: Tumor
How used: To determine whether treatment with a targeted therapy is appropriate

CD33

Cancer type: Acute myeloid leukemia
What’s analyzed: Blood
How used: To determine whether treatment with a targeted therapy is appropriate

Chromogranin A (CgA)

Cancer type: Neuroendocrine tumors
What’s analyzed: Blood
How used: To help in diagnosis, assessment of treatment response, and evaluation of recurrence

Chromosome 17p deletion

Cancer type: Chronic lymphocytic leukemia
What’s analyzed: Blood
How used: To determine whether treatment with a certain targeted therapy is appropriate

Chromosomes 3, 7, 17, and 9p21

Cancer type: Bladder cancer
What’s analyzed: Urine
How used: To help in monitoring for tumor recurrence

Circulating tumor cells of epithelial origin (CELLSEARCH®)

Cancer types: Metastatic breast, prostate, and colorectal cancers
What’s analyzed: Blood
How used: To inform clinical decision making, and to assess prognosis

Cytokeratin fragment 21-1

Cancer type: Lung cancer
What’s analyzed: Blood
How used: To help in monitoring for recurrence

Des-gamma-carboxy prothrombin (DCP)

Cancer type: Hepatocellular carcinoma
What’s analyzed: Blood
How used: To monitor the effectiveness of treatment and to detect recurrence

DPD gene mutation 

Cancer types: Breast, colorectal, gastric, and pancreatic cancers
What’s analyzed: Blood
How used: To predict the risk of a toxic reaction to 5-fluorouracil therapy

EGFR gene mutation

Cancer type: Non-small cell lung cancer
What’s analyzed: Tumor
How used: To help determine treatment and prognosis

Estrogen receptor (ER)/progesterone receptor (PR)

Cancer type: Breast cancer
What’s analyzed: Tumor
How used: To determine whether treatment with hormone therapy and some targeted therapies is appropriate

FGFR2 and FGFR3 gene mutations

Cancer type: Bladder cancer
What’s analyzed: Tumor
How used: To determine whether treatment with a certain targeted therapy is appropriate

Fibrin/fibrinogen

Cancer type: Bladder cancer
What’s analyzed: Urine
How used: To monitor progression and response to treatment

FLT3 gene mutations

Cancer type: Acute myeloid leukemia
What’s analyzed: Blood
How used: To determine whether treatment with certain targeted therapies is appropriate

Gastrin

Cancer type: Gastrin-producing tumor (gastrinoma)
What’s analyzed: Blood
How used: To help in diagnosis, to monitor the effectiveness of treatment, and to detect recurrence

HE4

Cancer type: Ovarian cancer
What’s analyzed: Blood
How used: To plan cancer treatment, assess disease progression, and monitor for recurrence

HER2/neu gene amplification or protein overexpression

Cancer types: Breast, ovarian, bladder, pancreatic, and stomach cancers
What’s analyzed: Tumor
How used: To determine whether treatment with certain targeted therapies is appropriate

5-HIAA

Cancer type: Carcinoid tumors
What’s analyzed: Urine
How used: To help in diagnosis and to monitor disease

IDH1 and IDH2 gene mutations

Cancer type: Acute myeloid leukemia
What’s analyzed: Bone marrow and blood
How used: To determine whether treatment with certain targeted therapies is appropriate

Immunoglobulins

Cancer types: Multiple myeloma and Waldenström macroglobulinemia
What’s analyzed: Blood and urine
How used: To help diagnose disease, assess response to treatment, and look for recurrence

JAK2 gene mutation

Cancer type: Certain types of leukemia
What’s analyzed: Blood and bone marrow
How used: To help in diagnosis

KRAS gene mutation

Cancer types: Colorectal cancer and non-small cell lung cancer
What’s analyzed: Tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate

Lactate dehydrogenase

Cancer types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma
What’s analyzed: Blood
How used: To assess stage, prognosis, and response to treatment

Microsatellite instability (MSI) and/or mismatch repair deficient (dMMR)

Cancer types: Colorectal cancer and other solid tumors
What’s analyzed: Tumor
How used: To guide treatment and to identify those at high risk of certain cancer-predisposing syndromes

Neuron-specific enolase (NSE)

Cancer types: Small cell lung cancer and neuroblastoma
What’s analyzed: Blood
How used: To help in diagnosis and to assess response to treatment

Nuclear matrix protein 22

Cancer type: Bladder cancer
What’s analyzed: Urine
How used: To monitor response to treatment

PCA3 mRNA

Cancer type: Prostate cancer
What’s analyzed: Urine (collected after digital rectal exam)
How used: To determine need for repeat biopsy after negative biopsy

PML/RARα fusion gene

Cancer type: Acute promyelocytic leukemia (APL)
What’s analyzed: Blood and bone marrow
How used: To diagnose APL, to predict response to all-trans-retinoic acid or arsenic trioxide therapy, to assess effectiveness of therapy, to monitor minimal residual disease, and to predict early relapse

Prostatic Acid Phosphatase (PAP)

Cancer type: Metastatic prostate cancer
What’s analyzed: Blood
How used: To help in diagnosing poorly differentiated carcinomas

Programmed death ligand 1 (PD-L1)

Cancer types: Non-small cell lung cancer, liver cancer, stomach cancer, gastroesophageal junction cancer, classical Hodgkin lymphoma, and other aggressive lymphoma subtypes
What’s analyzed: Tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate

Prostate-specific antigen (PSA)

Cancer type: Prostate cancer
What’s analyzed: Blood
How used: To help in diagnosis, to assess response to treatment, and to look for recurrence

ROS1 gene rearrangement

Cancer type: Non-small cell lung cancer
What’s analyzed: Tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate

Soluble mesothelin-related peptides (SMRP)

Cancer type: Mesothelioma
What’s analyzed: Blood
How used: To monitor progression or recurrence

Somatostatin receptor

Cancer type: Neuroendocrine tumors affecting the pancreas or gastrointestinal tract (GEP-NETs)
What’s analyzed: Tumor (by diagnostic imaging)
How used: To determine whether treatment with a particular type of targeted therapy is appropriate

T-cell receptor gene rearrangement

Cancer type: T-cell lymphoma
What’s analyzed: Bone marrow, tissue, body fluid, blood
How used: To help in diagnosis; sometimes to detect and evaluate residual disease

Thiopurine S-methyltransferase (TPMT) enzyme activity or TPMT genetic test

Cancer type: Acute lymphoblastic leukemia
What’s analyzed: Blood and buccal (cheek) swab
How used: To predict the risk of severe bone marrow toxicity (myelosuppression) with thiopurine treatment

Thyroglobulin

Cancer type: Thyroid cancer
What’s analyzed: Blood
How used: To evaluate response to treatment and to look for recurrence

UGT1A1*28 variant homozygosity

Cancer type: Colorectal cancer
What’s analyzed: Blood and buccal (cheek) swab
How used: To predict toxicity from irinotecan therapy

Urine catecholamines: VMA and HVA

Cancer type: Neuroblastoma
What’s analyzed: Urine
How used: To help in diagnosis

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)

Cancer type: Breast cancer
What’s analyzed: Tumor
How used: To determine aggressiveness of cancer and guide treatment

FoundationOne® CDx (F1CDx) genomic test

Cancer type: Any solid tumor
What’s analyzed: Tumor
How used: As a companion diagnostic test to determine whether treatment with a particular type of targeted therapy is appropriate

5-Protein signature (OVA1®)

Cancer type: Ovarian cancer
What’s analyzed: Blood
How used: To pre-operatively assess pelvic mass for suspected ovarian cancer

 17-Gene signature (Oncotype DX GPS test®)

Cancer type: Prostate cancer
What’s analyzed: Tumor
How used: To predict the aggressiveness of prostate cancer and to help manage treatment

21-Gene signature (Oncotype DX®)

Cancer type: Breast cancer
What’s analyzed: Tumor
How used: To evaluate risk of distant recurrence and to help plan treatment 

46-Gene signature (Prolaris®)

Cancer type: Prostate cancer
What’s analyzed: Tumor
How used: To predict the aggressiveness of prostate cancer and to help manage treatment

70-Gene signature (Mammaprint®)

Cancer type: Breast cancer
What’s analyzed: Tumor
How used: To evaluate risk of recurrence