Tumor markers are useful in that they serve as:

early detectors of cancer in those at-risk.

indicators of prognosis.

monitors of therapy and detection of residual disease .

noninvasive method of detection of recurrence.

ALPHA FETOPROTEIN (AFP)

Alpha fetoprotein is normally produced in the liver and yolk sac of the fetus and is elevated in the fetal blood. It is replaced by albumin postpartum and is generally no more than 16ng/ml after 6 months of age. Alpha fetoprotein is the most useful tumor marker for the diagnosis and management of hepatocellular carcinoma.

Alpha fetoprotein is transiently elevated in pregnancy and benign liver disease; in these cases the AFP is distinguished by a microheterogeneity of a carbohydrate moiety. Alpha fetoprotein levels greater than 500 ng/ml usually signal hepatocellular cancer.

More than 70% of patients with non-seminomatous testicular cancer have elevated alpha fetoprotein levels. Testing both AFP and b HCG increases the reliability of prognosis of nonseminoma. Serial testing after surgery* can monitor tumor load. AFP is not elevated in seminomas; increased levels rule out the presence of a pure seminoma. Management of seminoma patients should include AFP testing because patients with pure primary sominomas may develop nonseminomatous metastases.

*Note: The biological half life of alpha fetoprotein is approximately five days.

BETA₂-MiICROGLOBULIN (b_2-M)

Human b₂-microglobulin is part of the HLA-A, -B, -C antigens expressed on the surface of most nucleated cells; a component of the complex which binds antigens for presentation. The high level of b₂-microglogulin is because it is expressed on blood cells and subsequently released into the serum. The upper normal ranges from 2.0-2.5 m g/ml *. Beta₂-microglobuin is used an adjunct test for active disease, cell turnover, and tumor presence. Increased b ₂-microglogulin is also seen in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome and Crohn disease. Impaired renal funcion inhibits b₂-microglobulin clearance and results in elevated serum b₂-microglobulin. In HIV infections, b₂-microglobulin is frequently elevated.

Although b₂-microglobulin is elevated in tumors, it is clinically used for lymphoproliferative diseases including, leukemia, lymphoma, and multiple myeloma, where serum b₂-microglobulin is related to tumor cell load, prognosis, and disease activity. When the b₂-microglobulin level, which correlates to the myeloma cell mass and tumor growth rate, exceeds 4.0 m g/ml, the survival time is short. With levels > 6.0 m g/ml, the response to chemotherapy is poor. b₂-microglobulin is also useful in staging myeloma patients: in stage I patients, serum levels are < 6.0 m g/ml and albumin is >30 mg/ml; in stage II, serum levels are >6.0 m g/ml and albumin is > 30 m g/ml; in stage III serum levels are >6.0 m g/ml and albumin is < 30 mg/ml.

CSF levels of b ₂-microglobulin are sometimes elevated in CNS acute lymphoblastic leukemia (ALL), lymphoma, and lymphoproliferative diseases, but these levels are not helpful in early detection of CNS acute lymphoblastic leukemia in children. Progressive decrease of b ₂-microglobulin in CSF correlates with improvement of neurological disease in myeloproliferative disorders.

*Note: Most other tumor markers have values in the ng/ml range.

HUMAN CHORIONIC GONADOTROPIN (b HCG)

Human chorionic gonadotropin (b HCG), a normal placental hormone, is elevated in the urine and serum during pregnancy, and present in trace amounts (<0.3 IU/2) in normal sera. b HCG is effective for monitoring therapy response and tumor recurrence in nonseminomas (>60% have elevated b HCG).

CA19-9

CA19-9 is present on the glycolipids and glycoproteins of certain lipids of certain tumors.

CA19-9 is not organ specific and is elevated in a variety of adenocarcinomas. The highest sensitivity is for pancreatic, gastric, and hepatobiliary cancers. The upper limit of normal is 37 U/ml. CA19-9is the gold standard marker for pancreatic cancer with computed tomography used to differentiate benign from malignant. At levels >1000 U/ml pancreatic adenocarcinomas are resectable.

Acute cholangitis and cirrhosis (both benign) may have significantly elevated levels of CA19-9.

Note: 7% of the U.S. population and 20% of the japanese population do not express CA19-9 leading to false-negatives.

CA 125

CA 125 is expressed on the surface of coelomic epithelium and ovarian carcinoma cells. CA 125 is found in most serous, endometrioid and clear cells carcinomas of the ovary; mucinous tumors express CA 125 less frequently. Normal ovaries do not express CA 125, except in inclusion cysts and areas of metaplasia. Cardiac or liver disease, as well as breast, pulmonary tree or gastrointestinal tract tumors can also elevate CA 125 levels

In the presence of an adnexal mass, a CA 125 level ³ 200U/ml is significantly associated with ovarian cancer. Sometimes with chemotherapy, tumor cells no longer express, CA 125, and 25% will have tumor at second look laparotomies. Therefore a negative result does not rule out tumor recurrence. A positive result is an indicator for second look laparotomy.

Mesotheliomas as well as adenocarcinomas of the endometrium, endocervix and fallopian tubus are CA 125 positive as well.

CARCINOEMBRYONIC ANTIGEN (CEA)

Carcinoembryonic antigen is present in some malignant tissues and on the GI tract of normal embryos. Carcinoembryonic antigen is the most widely used tumor marker for GI cancer. Carcinoembryonic antigen is usually elevated in disseminated disease, but not in localized disease. Over 80% of patients with colorectal cancer and serum CEA >200 ng/ml have disease recurrence within 14 months of surgery.

CEA is often elevated in cirrhosis, with 88% of patients having a CEA of 3.0 ng/ml. CEA levels greater than 10 ng/ml are suggestive of hepatic cancer. CEA is transiently increased after surgical treatment, therefore testing is recommended 2-4 afterwards to avoid false-positives. CEA in pleural fluid is indicative of malignant effusion.

PROSTATIC ACID PHOSPHATASE (PAP) / PROSTATIC SPECIFIC ANTIGEN (PAS)

Prostatic acid phosphatase is an intracellular enzyme in the prostate gland. Leakage of the prostate fluid into the circulation results in elevated serum levels. Serum levels may be artificially elevated after palpation of the prostate; PAP 24-48hrs and PSA 72hrs).

Prostatic acid phosphatase used to be the serum marker for detection of prostate cancer for many years but is now used only as an adjuct to prostatic specific antigen. Prostatic specific antigen is more reliable than prostatic acid phosphatase for detection and monitoring of prostatic cancer. A few studies have shown prostatic acid phosphatase to be more specific but less sensitive than prostatic specific antigen therefore supporting the use of PAP with PSA.

Prostatic specific antigen is only produced by the prostate and in the seminal plasma, and is the major protein in seminal plasma.

Prostatic specific antigen, a normal constituent in prostate and is leaked into the circulation in those with prostate cancer.

PSA levels should be virtually undetectable after prostatectomy or radiation treatment. Even low levels (>0.2 ng/ml) indicate residual tumor.

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