tumor marker

TUMOUR MARKERS
Definition: Tumor markers are substances that can reflect the presence or progress of a tumor. They include substances, including enzymes, proteins and smaller peptides, which are secreted into body fluids by tumors, and antigens expressed on cell surfaces.
An ideal secreted tumor marker could be used for:
• screening
• diagnosis
• prognosis
• monitoring treatment
• follow-up to detect recurrence.
Classification of tumor markers:
1-Enzyme and isoenzyme
2-Hormones
3-Oncofetal antigens
4-Carbohydrate epitopes
5-Receptors
6-Oncogen product and genetic changes
The drawbacks of tumor markers
• Almost everyone has a small amount of these markers in their blood, so it’s very hard to spot early cancers by using these tests.
• The levels of these markers tend to get higher than normal only when there’s a large amount of cancer present.
• Some people with cancer never have high tumor marker levels.
• Even when levels of these markers are high, it doesn’t always mean cancer is present. For example, the level of the tumor marker CA 125 can be high in women with gynecologic conditions other than ovarian cancer.
• Because cancer is many different diseases, no single tumor marker can be used to look for all types of cancer.
These are the reasons why, today, tumor markers are used mainly in patients who have already been diagnosed with cancer to watch their response to treatment or look for the return of cancer after treatment.










?¬-Fetoprotein
?¬-Fetoprotein is a glycoprotein of molecular weight 67 kDa. It is synthesized by the yolk sac and the fetal liver and gut. In the fetus, it is a major plasma protein, however in adults, the normal concentration is less than 10 µg/L. Increased plasma concentrations of ?¬-fetoprotein are seen in normal pregnancy.
?¬-Fetoprotein is a valuable marker for hepatocellular carcinomas (HCC) and testicular teratomas. Overall, primary liver cancer is uncommon in the UK, and therefore population screening for the condition cannot be justified. However, some groups of patients - notably those with cirrhosis, persistence of hepatitis B virus and haemochromatosis - are at particularly high risk, and selective screening (e.g. at six-monthly intervals) using ?¬-fetoprotein measurement may be of value. ?¬- Fetoprotein concentrations are elevated in the majority of patients with cirrhosis and HCC, although in only about half those with tumors in the absence of cirrhosis. A concentration of >500 µg/L in a patient with cirrhosis is virtually diagnostic of HCC. The finding of concentrations in the range 50-500µg/L warrants further investigation. As a tumor marker in this context, ?-fetoprotein lacks specificity: concentrations of up to 100 µg/L can occur in cirrhosis in the absence of malignancy, ? -Fetoprotein does not appear to be of value prognostically. However, in histologically confirmed liver cancer, serial measurements of ? -fetoprotein are of considerable value in monitoring the response of the patient to treatment. The normal hepatic regeneration that occurs following partial hepatic resection may cause an increase in ? -fetoprotein concentration, but this is only transient.
In patients with testicular teratomas, ?-fetoprotein measurements are valuable in assessing prognosis, in staging and in monitoring therapy. A very high concentration indicates a massive tumor load and a poor prognosis (a mortality rate greater than 40% if ?-fetoprotein concentration is greater than 1.26 mg/L). A rapid fall to normal after orchidectomy implies that the disease was limited to the testis. Remission is achieved in 80% of patients with metastatic teratoma of the testis, using a combination of surgery and chemotherapy. The efficacy of treatment can be assessed from the decline in plasma ?-fetoprotein concentration, which reflects the decrease in tumor mass. Once a patient is in remission, repeated measurements are essential; a rise in concentration will be due to recurrence of the tumor and indicates the need for further treatment or a change in the chemotherapeutic regimen. It should be appreciated that plasma concentrations of ?-fetoprotein within the normal range are compatible with the presence of tumour; a rise in concentration, even if within this range, should raise the suspicion of tumor recurrence. On the other hand, tumors may lose the ability to secrete ? -fetoprotein, so vigorous clinical assessment remains an important part of the follow-up of these patients. Teratomas comprise some 32% of all testicular tumours. More common are seminomas (40%) but these rarely secrete either ?-fetoprotein or ?hCG, another marker for teratomas .
Carcinoembryonic antigen (CEA)
¬ Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birthThis tumour marker is present in elevated concentrations in the plasma of 60% of patients with colorectal cancer, more commonly so with advanced disease (80-100% if hepatic metastases are present) than with tumors confined to the colon. However, elevated concentrations are also found in a variety of non- malignant conditions, including liver disease of various types, pancreatitis and inflammatory bowel disease, and in some people who smoke heavily. CEA is neither sufficiently specific nor sensitive to be used in screening for colorectal carcinoma. CEA concentrations in plasma correlate poorly with tumor bulk, which limits the usefulness of measurements in monitoring treatment. Following surgical resection of a tumor, plasma CEA concentration can be expected to fall. However, while a subsequent rise suggests a recurrence, recurrence is not always heralded by such a rise and, even when it is, it may not affect the clinical outcome since further treatment may not be feasible.
¬Human chorionic gonadotrophin (hCG)
hCG is a hormone produced by the normal placenta, reaching a maximum concentration in plasma by the eighth week of pregnancy, hCG is composed of an ?-and ?-subunit: the ?-subunit is identical to that of luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH); the ?- subunit, however, is specific to hCG and is therefore
measured in assays for the hormone. The presence of hCG in the plasma at other times indicates the presence of abnormal trophoblastic tissue or a tumor secreting the hormone ectopically. ?hCG is an almost ideal tumor marker for choriocarcinoma, a malignant proliferation of chorionic villi that may develop from hydatidiform mole, itself a potentially malignant proliferation of this tissue, which occurs in approximately 1 in 2000 pregnancies in the UK. Hydatidiform mole is treated by uterine curettage, but the patient is at risk of developing choriocarcinoma if removal is incomplete. hCG is an extremely sensitive tumor marker; tumors weighing only 1 mg may be detectable. All patients who have had hydatidiform moles must be followed up with regular checks of plasma hCG concentration. Should a tumor develop, the marker can be used as an indicator of the response to treatment and, if this is successful, in long-term follow-up thereafter.
hCG is also secreted by approximately 50% of testicular teratomas and should be measured together with ?- fetoprotein in the follow-up of patients after treatment of the tumor. Since LH concentrations rise after orchidectomy, it is important that an assay specific to the ?-chain of hCC is employed, to avoid cross-reaction causing an apparent increase in hCG.
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