Tumor Markers

Clinical Pathology

DR INTANRI KURNIATI ., SP.PK

BAGIAN PATOLOGI KLINIK
FAKULTAS KEDOKTERAN UNIVERSITAS LAMPUNG
Definition

• Tumor markers are oncoproteins or mutated

forms of these proteins that can indicate the
presence of a tumor.
• Oncoproteins are products of mutated
oncogenes – become permanently activated in
stimulating cell growth and proliferation
 Tumor Markers associated with Cell Proliferation
 Benignand nonmalignant diseases may also
involve elevated levels
 NOT SUITABLE FOR SCREENING OR CANCER
DIAGNOSIS due to large number of FALSE-
POSITIVE results • Useful in MONITORING during
treatment
 Tumor Markers related to Metastasis
 Cell
products released and synthesized during the
process of metastasis.
 Indicate
risk of occurrence of metastases or poor
prognosis
 Measurements are limited to tumor tissues and tumor
tissue cytosols.
 Monocolonal Antibody-Defined Tumor
Markers
 Hybridoma technology used to focus on
only a small surface area, an EPITOPE or
ANTIGENIC DETERMINANT using monoclonal
antibodies.
 There are no TUMOR-SPECIFIC EPITOPES, only
TUMOR-ASSOCIATED EPITOPES
 Monocolonal Antibody-Defined Tumor Markers
 Much more specific and sensitive than polyclonal
antibodies – Ex. CA 19-9, CA125 and CA15-3 are
much more sensitive and specific than CEA for
pancreatic, ovarian and breast CA, respectively.
KNOW THE SENSITIVITY AND SPECIFICITY!

 SENSITIVITY  SPECIFICITY
 100%sensitivity  100% specificity means
means that the test that it will identify only
the patients with the
can detect all specific type of disease
patients with that and not those without
disease the disease.
 CLINICAL APPLICATIONS OF TUMOR
MARKERS  SCREENING

 NONE of the tumor markers discovered had the specificity

and sensitivity for screening.
 Screening is not recommended especially to an
asymptomatic population.
 Exceptions: – Screening for primary hepatoma in China
using AFP, due to high incidence
 Screening for prostate CA with PSA and DRE due to tissue
specificity of PSA and high incidence in men >50
DIAGNOSIS

 The frequency of detecting elevated levels of

tumor markers in nonmalignant diseases and
the overlap observed between the normal
concentrations and the concentrations of tumor
markers in patients with proven cancer
discourages their use in diagnosis
MONITORING TREATMENT

 One of the two most useful applications of tumor

markers
 The serum level of tumor markers reflects well
the success of surgery or the efficacy of
chemotherapy
DETECTION OF RECURRENCE

 Second most useful application

 The appearance of most of the circulating tumor
markers has a “lead time” of several months (3-6
months) prior to the stage at which many of the
physical procedures could be used for the
detection of the cancer
 The specificity of tumor markers does not present a
problem for this application.
PROGNOSIS

 The risk factors associated with the process of

tumor metastases such as proteases and
adhesion molecules are usually better markers
for predicting prognosis.
 Most of these are measured in tumor tissues and
cytosols.
 RECOMMENDATIONS FOR ORDERING TUMOR
MARKER TESTS
1. Never rely on the result of a single test
2. When ordering serial testing, be certain to order every test from the same
laboratory using the same assay kit
3. Be certain that the tumor marker selected for monitoring recurrence was
elevated in the patient prior to surgery – BASELINE!!!!
4. Consider the half-life of the tumor marker when interpreting the test result
5. Consider how the tumor marker is removed or metabolized from the blood
circulation – KIDNEY AND LIVER
6. Consider ordering multiple markers to improve the sensitivity and specificity for
diagnosis
7. Order the nonspecific markers for cost-saving and for their high sensitivity.
8. Be aware of the presence of ectopic tumor markers
CA 125

 Expressed by greater than 80% of nonmucinous

epithelial ovarian carcinomas.
 Serous, endometrioid and clear cell carcinomas of
ovary
 Patients undergoing chemotx may show a false decline
and a negative result does not always rule out tumor
recurrence.
 Also used for follow-up on uterine tumors and in
endometriosis
 Prostate-Specific Antigen -PSA

 The best tumor marker discovered thus far due to its tissue specificity
 Useful for screening and for management of prostate CA
 Lack of cancer specificity is the only drawback; also elevated in BPH,
prostatitis, and infarction
 Useful in monitoring success of surgical prostatectomy
 A transient and modest increase may occur during radiation therapy and
should not be misinterpreted as disease progression • Useful in detecting
recurrence
 In combination with DRE is a good screening tool
Free PSA

 Measurement of free PSA and calculation

of %fPSA has been used to help
differentiate between BPH from prostatic
CA.
 %fPSA = (fPSA / PSA) x 100
 >23% associated with BPH
 <6% associated with prostatic CA
Thank you