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Laboratory Medicine

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sajwa baqader

on 16 March 2016

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Transcript of Laboratory Medicine

Tumor Markers
Presented by:
Nada Bahatheq & Eman Al.theeb
Supervised by:
Dr.Abdullhaleem Ali
Tumor markers are substance produced by a tumor or a host response to a tumor that can differentiate tumor from normal tissue.

These substances can be found in : blood, urine or tumor tissue.
They are gene products often produced by normal tissues in low levels and circulate normally in blood in small quantities.

Elevations of tumor markers level are usually derived from tissues normally producing that marker or from embryologically related tissues (i.e. CEA from colon or stomach; liver; pancreas).

Most tumor markers are not specific for a single cancer; they found with different tumors of the same tissue type (tumor-associated markers).
Ideal Characteristics of Tumor Markers
1.Easy to measure in blood.
2.Positive early in the development of malignancy.
3.Organ specific
4.Tumor specific.
5.Highly sensitive.
Note:
There is no ideal tumor marker
for all tumour markers, some healthy individuals will have values outside the reference interval.

Tumor marker levels are not altered in all people with cancer especially in early stage: A normal result does not exclude malignancy.

Level of the same tumor marker can be altered in more than one type of cancer.
" If the tumor marker tests are
negative
?
it's good news, but you must always remain vigilant.


" If the tumor marker tests are
positive
?
This does not necessarily mean that you have a
cancer. If your reading is above normal, a visit
to a doctor is highly recommended.
Clinical Use of Tumor Markers

Monitoring therapy:
a decrease or return to a normal level may indicate that the cancer is responding to therapy, whereas an increase may indicate that the cancer is not responding.
Clinical staging and prognosis:
tumor marker level reflects the stage (extent) of the disease.
Detection of recurrence after treatment has ended.

Most tumor markers should not be used as a “cancer screening tool”.
Common Types of Tumor Markers:
Enzymes
Hormones
Oncofetal antigens
Carbohydrate related antigens
Enzymes:

Prostate-Specific Antigen (PSA):
Normal value :
< 4 ng/ml

PSA seems to be an ideal tumor marker ..!
(Tissue specificity)
.

it is serine protease, glycoprotein, lyses the seminal clot and found in normal prostatic epithelium and secretions but not in other tissues.
Enzymes:

Prostate-Specific Antigen (PSA):
PSA is highly sensitive for the presence of prostatic cancer.

PSA is detectable in normal men and often is elevated in benign prostatic hypertrophy, which may limit its value as a screening tool for prostate cancer.
Hormone:

Human chorionic gonadotrophin (HCG):
Secreted by trophoblast cells of normal placenta
Marker for pregnancy.

Normal value :
In men: < 2.5 U/ml
In non-pregnant women:
< 5.0 U/ml
Increased in all patients with placental trophoblastic disease e.g.:

-choriocarcinoma
-vesicular mole
-Increased in 70% of non seminomatous testicular malignancies.
Hormone:

Human chorionic gonadotrophin (-HCG):
Oncofetal antigens
Alpha-fetoprotein (AFP):
Glycoprotein synthesized by the fetal yolk sac and liver.

Biochemically almost identical to adult albumin.

Normal value :
0-15 IU/ml
Oncofetal antigens
Alpha-fetoprotein (AFP):
Elevated values in adults usually signify malignancy, either hepatocellular carcinoma or germ cell tumors containing a yolk sac component.

Elevated low levels (20-200 ng/mL) should increase the index of suspicion for hepatocellular carcinoma (hepatoma). However patients with hepatitis and cirrhosis may have slight to moderate elevations of AFP in this range.


NOTE:
AFP is best used for monitoring treatment, determining prognosis or detecting tumor recurrence.
Oncofetal antigens
Cell surface glycoprotein cell adhesion molecule.



Its adult normal range:
< 2.5 ng/mL (non smoker)
< 5 ng/mL (smoker).
Oncofetal antigens
Carcinoembryonic Antigen (CEA):
Colorectal cancer 70%.
Pancreatic carcinoma 55%.
Breast carcinoma 40%.
Lung carcinoma 40%.
Uterine carcinoma 40%.
Carbohydrate related markers
Cancer Antigen 125 (CA - 125):
Expressed by ovarian epithelium.
Normal value :
0-35 U/ml

Ca-125 is increased in Approximately 50% of stage 1 ovarian carcinomas, And in approximately 90% of stage 3 & 4 ovarian carcinomas.
Carbohydrate related markers
Cancer Antigen 125 (CA - 125):
- Low positive levels suggest better prognosis.

- CA-125 is good for monitoring progression of disease and detection of recurrent or minimal residual disease (approximately 75% accurate).
Carbohydrate related markers
Cancer antigen 15-3 (CA 15-3):
Increased in approximately 23% of breast carcinomas

Normal value :
< 31 U/ml

Used for monitoring and disease progression after diagnosis.


Approximately 69% of women with
metastatic breast carcinoma
show increased levels.
Carbohydrate related markers
CA 15-3 can be elevated in other metastatic malignancies including:
-GI
-Ovary
-Lung
-Pancriatic

It is mildly elevated in some benign diseases.
Carbohydrate related markers
Cancer antigen 19.9 (CA 19.9):
CA 19.9 is a marker for pancreatic carcinoma colorectal carcinoma.

Normal value :
<37 U/ml

Elevated CA 19.9 levels have been noted in approximately
80% of patients with pancreatic cancer
,
67% of patients with hepatobiliary carcinoma
and
50% or less of patients with gastric and hepatocellular carcinoma.
Test methodology for some tumor markers
chemiluminescence immunoassay
Oncofetal antigens
Carcinoembryonic Antigen (CEA):
It is not useful for screening for the presence of malignancy: WHY ?

1- Mildly elevated in benign diseases and smoking .

2- Not elevated in some gastrointestinal tumors.

It is useful for clinical staging and likelihood of metastases, and highly useful in monitoring for recurrent disease following therapy.
Cancer antigen 15-3 (CA 15-3):
CA 19.9 is not useful in monitoring recurrence or early relapse.


Unfortunately, detection of early relapse for pancreatic cancer has little clinical significance since there is no known therapy for this disease.
Carbohydrate related markers
Cancer antigen 19.9 (CA 19.9):
COBAS
VIDAS
Overview
Common Cancer Terms
Cancer is the second leading cause of death in North America, accounting for > 500,000 deaths annually.

It is estimated that 45% of males and 38% of females will develop invasive cancer in their lifetime.
Biologically, cancer refers to the uncontrolled growth of cells that can develop into a solid mass or tumor & spread to other areas of the body.
The formation
(tumorigenesis)
& spreading
(metastasis)
of tumors are caused by a complex combination of inherited and acquired genetic mutations.

These acquired genetic mutations include:
1- activation of:
-growth factors e.g. Epidermal Growth Factor (EGF) & oncogenes (e.g. K-ras).
2- inhibition of:
-apoptosis -tumor suppressor -cell cycle regulation genes.
What is the tumor marker ?
Factors affecting cancer severity include:
-Tumor size
-Histology
-Regional lymph node involvement
-The presence of metastasis
For most solid tumors (e.g., breast, lung, kidney), cancer is broadly classified (using roman numerals I-IV) into 4 stages:
-stage I:
Localized primary tumor.
-Stage IV:
Metastasis and invasion of tumor to distant tissues.
Angiogenesis
Apoptosis
Cell cycle
Oncogene
Tumor suppressor gene
Encodes a protein that, when mutated, promotes uncontrolled cell growth
Encodes a protein involved in protecting cells from unregulated growth
Programmed cell death
Phases of cell activity divided into G, S, and M (growth, DNA synthesis, and mitosis, respectively)
Development of new blood vessels to supply oxygen and nutrients to cells
Carcinoembryonic Antigen (CEA):
Full transcript