Tumor Markers

Key Information

For baseline and observation — to assess tumor burden and monitor levels of tumor and indicate a recurrence; prognosis (what treatment to use if the tumor should recur); most tumor markers are NOT specific, meaning that positive result does not necessarily mean that the primary site can be readily identified.

Acid Phosphatase

Also called:

Acid phos, acid f, acid p'tase. A test of blood serum to detect a specific enzyme produced by several tissues, particularly the prostate. Acid phosphatase levels are elevated in 85% of cases with skeletal metastases, 60% of untreated cases, and 20% of localized cases. Usually ordered as a separate laboratory test. May also be ordered as prostatic acid phosphatase (PAP), a measure of acid phosphatase secreted by prostate gland cells specifically. Note:test results may be affected by recent prostatic massage or palpation; acid phosphatase level should be assayed before digital rectal examination. Normal range: varies according to method of processing the serum:

ACTH (Adrenocorticotropic Hormone)

Elevated level found in paraneoplastic syndrome caused by small cell carcinoma. Non-diagnostic of lung cancer, but an indicator of metastases.

Alkaline Phosphatase

Also called:

Alk phos, alk f, ALP. May be included in blood chemistry screening panel. Normal range: 20-90 I.U./liter. Normal range may vary somewhat according to the brand of laboratory assay materials used.

Alpha-fetoprotein

A serum test used as a tumor marker for hepatocellular cancer. Elevated alpha-fetoprotein levels are also found in certain ovarian and teratocarcinoma or embryonal carcinoma of the testis. Elevated alpha-fetoprotein levels are not found in other histologies of testicular cancer. Note: Observe the date of an alpha-fetoprotein study carefully. Record a pre-operative study only. Alpha-fetoprotein is also used as a marker postoperatively to monitor residual tumor. Also called: FP, AFP, alpha-fetoglobulin. Normal range: Adults: < 15 ng/ml.

bcl-2

Oncogene Analysis diagnostic method to differentiate B-cell and follicular types of lymphomas.

β-2 Microglobulin

Also called:

Beta 2-M. Elevated levels are present in lymphoproliferative disorders; nonspecific to chronic lymphocytic leukemia.

CA 15-3 (Cancer Antigen 15-3)

Elevated in 76% of metastatic breast cancers.

CA 19-9 (Cancer Antigen 19-9)

Monitors post-therapeutic gastrointestinal cancer for recurrence; nonspecific to stomach or colorectal cancer.

CA-125 (Cancer Antigen-125)

A tumor marker useful for monitoring for ovarian cancer by measuring an antigen to epithelial neoplasms circulating in blood serum. Normal range: 0 - 35 U/mL. Normal range may vary somewhat according to institutional experience. Levels above 35 suggest the presence of ovarian tumor.

CA 195 (Cancer Antigen 195)

Detects gastrointestinal cancers but cannot differentiate among primary sites; changing level indicates progression or regression of tumor load.

C219

Presence is associated with multidrug resistance.

CA 549 (Cancer Antigen 549)

Present in 50% of patients with advanced breast cancer.

Calcitonin

Elevated levels of this thyroid hormone occasionally occur with small cell lung cancer; increasing levels may indicate progression of disease.

Catecholamines

Helps distinguish tumor cell type; most useful in adrenal tumor.

Cathepsin D

Distinguishes node-negative patients who may recur (and therefore should receive adjuvant chemotherapy) from node-negative patients who probably will not recur. Elevation indicates a poorer prognosis.

CEA (Carcinoembryonic Antigen)

A blood test measuring the presence of an antigen in malignancies arising in entodermal (embryonic) or gastrointestinal tissue. Persistent elevated levels indicate residual or recurrent metastatic carcinoma. CEA assay is nonspecific for identifying a primary site, but it does indicate the presence of malignancy. Smokers may have an elevated CEA without malignant disease; smoking may affect accuracy of CEA results. Normal range: < 2.5 ng/ml. Normal range may vary somewhat depending on the brand of assay used. Levels > 10 ng/ml suggest extensive disease and levels > 20 ng/ml suggest metastatic disease.

C-erb B-2 (also called HER-2 or neu oncoprotein)

Associated with larger sized tumors, shorter relapse time and lower survival rate.

Chromogranin-A

Monitors tumor bulk in neuroblastoma, APUDoma, VIPoma, pheochromocytoma; non-diagnostic of central nervous system tumor.

C-myc DNA

Amplification elevated (amplified) in breast cancers in older women; juxtaposition of this chromosome with a heavy chain immunoglobulin occurs frequently in Burkitt's lymphoma and other B-cell lymphomas, as well as acute lymphoblastic leukemia.

DNA Studies

Also called:

Flow cytometery. Differentiates between tumors at high and low risk for recurrence. DNA studies are a prognostic tool for non-small cell lung and other solid tumors.

• Ploidy Analysis — Aneuploid tumors correlate with more aggressive behavior and a greater risk of recurrence. Diploid tumors have a better prognosis than aneuploid or tetraploid tumors
• S-Phase (also called Cell Cycle Analysis) — percentage of tumor cells synthesizing DNA; patients with high S-phase fraction have less favorable prognosis
• Proliferation Index — high rates indicate actively growing tumors and a greater risk of relapse

EFGR (Epidermal Growth Factor Receptor)

Negative EFGR results correlate with better prognosis regardless of ER status.

Estrogen Receptor Assay (ERA)

A laboratory test of breast cancer tissue to determine the responsiveness of the tumor to endocrine therapy or to removal of the ovaries. Tumors which are negative for estrogen receptors rarely respond to hormone manipulation; about 55% of ER positive tumors will respond to endocrine therapy. The unit of measurement is femtomoles (fmoles) per milligram of tumor. Test results — negative: 3 fmoles or less. ERA may not be performed if tumor is less than 1.0 cm in size or if tumor is completely in situ. Types of ERA: Quantified (measured in femtomoles or fmoles); Immunohistochemical—a qualitative measurement of the observed number of hormone responsive cells, reported as positive or negative.

Ferritin

Measures iron storage protein in sialic acid; low levels suggest good prognosis in head and neck malignancies, although test is nonspecific for head and neck cancer; elevated levels present in lymphoproliferative disease; may indicate Hodgkin disease or leukemia; monitors cause of disease in neuroblastoma; nonspecific in neurogenic tumors.

Flow Cytometry

See DNA Studies.

Gastrin

Differentiates gastrin secreting non-beta islet cell tumors of pancreas; levels above 1000 pg/ml are diagnostic of gastrinoma; also found in some benign conditions.

Glucagon

Differentiates alpha-cell tumors; levels above 900 are diagnostic of glucagonoma; also present in diabetes and other conditions.

5-HIAA (5-Hydroxy-Indol Acetic Acid)

Quantitative analysis of urine levels; levels above 15 mg/24 hours indicate malignant carcinoid tumors (argentaffinomas), which may also appear in stomach, appendix, or lower intestine.

Human Chorionic Gonadotropin (hCG) ? or ? a-HCG (Alpha Subunit HCG)

A nonspecific marker for pancreatic, pituitary, and placental tumors; elevated levels may be present in pancreatic cancer.

Beta Subunit HCG

A serum test used as a tumor marker for choriocarcinoma and for testicular carcinoma. Beta-HCG levels are never found in normal men. When the presence of B-HCG is detected in serum it always indicates a malignancy. Also called: &-HCG, beta-HCG, beta chain HCG. Note: Observe the date of the beta-HCG study carefully. Record a preoperative study only. Beta-HCG is also used as a marker postoperatively to monitor residual tumor and the effectiveness of therapy. In patients with choriocarcinoma who have had a hysterectomy and oophorectomy, the presence of beta-HCG will confirm the patient has residual cancer that requires further treatment. In patients with testicular cancer who have had an orchiectomy, the presence of beta-HCG will confirm the patient has residual cancer that requires further treatment. However, when beta-HCG does not exist in the serum, the presence of active cancer cannot be excluded, especially in patients who have been previously treated. Normal range: 0 ng/ml.

HVA (Homovanillic Acid)

Elevated levels suggest catecholamine-secreting tumor such as neuroblastoma or ganglioneuroma; high levels rule out pheochromocytoma.

Int-2 DNA Amplification

Elevation (amplification) associated with recurrence of tumor.

LDH (Lactic Dehydrogenase)

A blood chemistry study, usually part of a liver panel, useful in assessing liver and pulmonary disease. All tumors produce LDH. Normal range: total LDH levels range from 48 to 115 IU/liter. There are five tissue-specific isoenzymes that can be identified and measured. The distribution of isoenzymes is as follows:

• LDH1: 18.1% to 29% of the total (heart, red blood cells and kidneys)
• LDH2: 29.4% to 37.5% of the total (heart, red blood cells and kidneys)
• LDH3: 18.8% to 26% of the total (lungs)
• LDH4: 9.2% to 16.5% of the total (liver and skeletal muscles)
• LDH5: 5.3% to 13.4% of the total (liver and skeletal muscles)

Liver Function Tests (LFT)

A series of blood chemistry tests measuring enzymes excreted by the liver during abnormal functioning due to metastases, obstruction or other conditions. Also called: liver panel. A liver panel may contain any of the following tests. If any one of these tests is outside the normal range of values, the test should be reported as abnormal.

NSE (Neuron Specific Enolase)

Elevated level indicates presence of small cell carcinoma of lung and neuroblastoma; of secondary use in testicular neoplasms; nonspecific to central nervous system tumors.

Pancreatic Polypeptide

Diagnoses pancreatic gamma cell tumors; elevated in APUD-omas, VIP-omas, and MEN (Multiple Endocrine Neoplasia).

Philadelphia Chromosome (Ph1)

Presence of abnormal chromosome in bone marrow confirms diagnosis of chronic myelogenous leukemia; absence of Ph1 chromosome does not rule out CML.

PLAP (Placental Alkaline Phosphatase or PL-AP)

Differentiates the source of tumor among liver, bone, and germ cell origin; non-diagnostic by itself, it helps confirm malignancy in a small number of patients.

PLP (Parathyroid hormone-like Protein)

Elevated levels of this circulating hormone are found in squamous cell cancer and in breast cancer.

Progesterone Receptor Assay (PRA)

A laboratory test of breast cancer tissue to determine the responsiveness of the tumor to endocrine therapy or to removal of the ovaries. Progesterone receptor assay increases the reliability of estrogen receptor assay results: a positive progesterone receptor assay indicates greater likelihood that the patient will respond to hormone therapy. The unit of measurement is femtomoles (fmoles) per milligram of tumor. Test results — negative: 5 fmoles or less. Test may not be performed if tumor is less than 1.0 cm in size or if tumor is completely in situ. Types of PRA: Quantified (measured in femtomoles or fmoles); Immunohistochemical—a qualitative measurement of the observed number of hormone responsive cells, reported as positive or negative.

Proinsulin C-peptide

Differentiates cell type for endocrine-secreting tumors; elevated in insulinoma and islet cell tumors.

Prostate Specific Antigen

Also called:

PSA.

Excludes:

Prostatic acid phosphatase.

Tumor marker assay (test) of blood serum for antigen released from cells in prostate tissue. Value may be elevated in benign prostatic hypertrophy; greatest elevation occurs in stage C and D prostate cancer. After radical prostatectomy or radiation therapy, rising levels of PSA indicate residual disease or recurrence. Note: test results may be affected by recent prostatic massage or palpation; PSA level should be assayed before digital rectal examination.

Normal range: 0 - 4.0 ng/ml. Normal range also varies depending on the patient's age.

SMA (Vanillylmandelic Acid)

Elevated levels suggest catecholamine-secreting tumor such as neuroblastoma or ganglioneuroma; nonspecific to SMA.

Squamous Cell Carcinoma (SCC)

Antigen monitors tumor burden after treatment for squamous cell carcinoma; usually used for advanced disease; primary application is head and neck cancer, secondarily for lung cancer; nonspecific to cervical carcinoma but specific to squamous cell carcinoma.

Thyroglobulin

Elevated levels of this serum hormone are found in follicular carcinoma and return to normal following treatment if all tumor is removed; useful for monitoring residual disease and recurrence of follicular carcinoma.

TDT (Terminal Deoxynucleotidal Transferase)

Differentiates acute lymphocytic leukemia from acute non-lymphocytic leukemia; differentiates lymphoblastic lymphomas from other non-Hodgkin lymphomas; TDT levels are absent in patients in remission.

TPA (Tissue Polypeptide Antigen)

An antigen marker for cancers of gynecologic sites, bladder, and lung; nonspecific to ovarian and cancer; elevated levels indicate presence of malignancy; also used to monitor bladder and lung cancer in males.

a-TSH (Alpha Subunit Thyroid Stimulating Hormone)

A marker that can differentiate pancreatic from other hormonal tumors; nonspecific — also found in pituitary and placental tumors.