20 Tumor Markers

Tumor Markers

Produced by tissues in small amounts, elaborated by

neoplastic cells

Classified as metabolic consequences of:

1. Tumor burden
2. Endocrine associated abnormalities
3. Specific enzyme markers
4. Tumor antigens
5. Nucleic acid (gene) alterations

To predict or monitor cancer, marker should be:

1. Produced by all tumor of a particular type
2. Present in blood in quantities proportional
to the mass of the primary tumor and its
metastasis
Calcitonin
Secreted by the parafollicular cells of the thyroid in

response to elevated serum calcium concentrations

Overproduced in the medullary carcinoma of the

thyroid
Prostatic Acid Phosphatase (PAP)
Elevated in prostatic carcinoma particularly when

there is metastasis

Elevated in benign prostatic hypertrophy

Organ specific with high sensitivity but lesser

specificity

Not used as a general cancer screening procedure

Monitor recurrence of tumor after surgery or other

ablative treatment

Complemented with PSA

Creatine Kinase

Produced by:
1. Skeletal muscle (isoenzyme MM)
2. Smooth muscles and brain (BB)
3. Myocardium (MM & MB)

Ectopically released from neoplastic cells

Alkaline Phosphatase
Enzyme activity at alkaline pH

Elevated in

1. Metastatic carcinoma to the liver

2. Primary carcinoma of bone or bone
metastasis
3. Regan isoenzyme from placenta
(heat stable)
Human Chorionic Gonadotropin (HCG)

Glycoprotein produced by syncitiotrophoblasts of the

placenta

Secreted in:
1. Chroriocarcinoma
2. Hydatidiform mole
3. Testicular carcinoma (Germ cell)

Found in urine and serum; amount is directly

proportional to tumor mass

Applications:
1. Diagnosis of pregnancy
2. Monitor tumor recurrence after surgical
removal and chemotherapy
3. Convenient companion measurement with
fetoprotein in Testicular carcinoma

Carcinoembryonic Antigen

Glycoprotein; an oncofetal antigen

Not tumor specific

Elevated in:
1. GIT malignancies including pancreas
2. Lung malignancies
3. Breast malignancies
4. Ovarian malignancies

Not recommended for general cancer screening

Major monitoring parameter

For Colorectal cancer: a baseline measurement is
needed and CEA should return to normal after 4-6
weeks
1.
2.
3.
4.

Early detection of recurrence

Relapse after surgical removal of tumor, radiation or
chemotherapy
Persistent elevation may indicate incomplete
resection
Presence of metastasis
Guidelines
(American Society of Clinical Oncology-ASCO)
1. CEA should not be use as a screening test for
colorectal cancer
2. CEA may be used preoperatively in patients with
colorectal cancer to assist in staging and
planning treatment
3. CEA may be used every 2 or 4 months post
operatively if resection of liver metastasis would
be indicated
4. CEA may be used to monitor treatment of
metastasis

Alpha-Fetoprotein (FP)

Major serum protein in fetus; peak values at 14

weeks AOG
Analogous to albumin in adults

Oncofetal antigen expressed in some germ cell

tumors
Teratoblastoma
Testicular cancer
Ovarian cancer
Elevated in:

1. Hepatocellular carcinoma
2. Cirrhosis
3. Hepatitis
4. Necrosis
5. Metastatic liver disease
Prostate-Specific Antigen

Most common malignancy in males but only 6% die

from the malignancy

Enzyme is organ specific but measured as an antigen

by immunoassay

Typical screening test for prostatic cancer includes:

1. Digital rectal examination
2. PSA universally used for screening
3. Ultrasound
4. Needle biopsy for suspicious findings

rainwater@mymelody.com || 1st semester, AY 2011-2012

Guidelines
1. Age adjusted reference ranges (N.V. 4.0
ng/mL)
2. PSA velocity: annual increase of 1 ng/mL
indicative of prostatic cancer
3. PSA density or index =
serum PSA
_
prostate volume (by UTZ)
4. Quantitative free and bound PSA
PSA present in 3 forms:
1. free PSA
2. PSA complexed with ACT (1 anti-chymotrypsin)
3. PSA complexed with AMG (2 macroglobulin)

Cancer Antigen 125 (CA 125)

Cancer antigen or carbohydrate antigen

Glycoprotein found in:

1. Fallopian tubes
2. Endometrium
3. Endocervix

Not tumor specific but elevated in 1-2% of women

during:
1. Ovulation
2. Normal endometrium
3. Pelvic inflammatory disease (PID)

Elevated in:
1. Ovarian cancer serum levels do not
correlate well with tumor size
2. Adenocarcinoma of cervix
3. Adenocarcinoma of fallopian tubes
4. Lung cancer
5. GIT cancer

Not used for screening ovarian cancer

Used to monitor response and recurrence in women

treated for ovarian cancer

Estrogen/Progesterone Receptors

For breast and endometrial cancer

Used in predicting tumor response to manipulative

endocrine therapy such as:

1. Estrogen antagonist
2. Ablation of estrogen secretion sites
(oophorectomy)

Interaction of estrogen with ER stimulates production

of PR

PR strong indicator that estrogen and ER are

functional
ER+: noted in of breast cancer
ER-: grow faster, > cell division
ER+ PR+: responds to endocrine stimulation
ER- PR+: no response
Other Markers for Breast Cancer
1. Cathepsin D
2. DNA ploidy
3. Epidermal growth factor receptor
4. HER 2/New oncoprotein
Human Papilloma Virus (HPV)

Causes:
1. Skin warts
2. Condyloma acuminatum
3. Cervical cancer

HPV 6, 11 = low grade malignancy

HPV 31, 33, 35 = intermediate grade malignancy
HPV 16,18 = high grade malignancy

CA 15-3

Antigen measured with 2 distinct antibodies:

1. 115 D8
2. DF 3
Elevated in:
1. Breast cancer
2. Lung cancer
Not used for screening
Used to monitor response of metastatic disease in the
absence of other measurement of disease
progression

CA 19-9

Mucin glycoprotein identical to the Lewis blood group

detected in:
1. Pancreas
2. Gallbladder
3. Prostate
4. Stomach
5. Colon
6. Ovary
7. Lung
Elevated in 80% of patients witn pancreatic cancer
Used to monitor disease progression

rainwater@mymelody.com || 1st semester, AY 2011-2012