A basic tenet of tumor immunology is that when a normal cell transforms into a malignant cell, it produces specific antigens not found in mature normal cells. A tumor marker, such as a hormone or enzyme, is a substance found in or created by a tumor, or by the host in response to a tumor, that can be used to distinguish a tumor from normal tissue or to determine if a tumor is present. Tumor marker activity can also be seen in non-cancerous settings. Biochemical, immunochemical, and molecular methods can be used to quantify tumor markers in tissues and body fluids.
Patients with prostate, breast, and bladder cancers rely heavily on tumor markers for diagnosis and monitoring.
ALP and collagen-type markers in bone cancer, Igs in myeloma, catecholamines and their derivatives in neuroblastoma and pheochromocytoma, and serotonin metabolites in carcinoid are all older, well-established markers. Hormone receptors, cathepsin D, HER/neu oncogenes, and plasminogen receptors and inhibitors are among the many prognostic markers found in breast tissue. The number of tumor markers approved by the Food and Drug Administration continues to increase. Some forms of cancer can benefit from the use of multiple marker combinations.
List of Some tumor-specific markers
The following are examples of tumor-specific markers:
- Beta subunit of human chorionic gonadotropin (β-hCG)
- Alpha fetoprotein (AFP)
- CA 15-3
- CA 19-9
- CA 27.29
- CA 125
- PSA and prostatic acid phosphatase
- Other enzyme markers
- Other hormone markers
The fetal liver and yolk sac usually synthesize AFP. Hepatocarcinoma, endodermal sinus tumors, nonseminomatous testicular cancer, teratocarcinoma of the testis or ovary, and malignant tumors of the mediastinum and sacrococcyx all secrete AFP in nanogram to milligram amounts in the serum. Furthermore, AFP levels may be elevated in a limited percentage of patients with gastric and pancreatic cancer who have metastasized to the liver. Since one or both markers may be secreted in 85 percent of teratocarcinoma patients, both AFP and β-hCG should be measured at the outset in all patients with the disease. In non-cancerous conditions such as hepatitis and cystic fibrosis, AFP levels may be elevated.
AFP is a highly accurate marker for monitoring a patient’s response to chemotherapy and radiation. The levels should be checked every 2 to 4 weeks (in vivo, the metabolic half-life is 4 days).
Beta Subunit of Human Chorionic Gonadotropin
β-hCG, an ectopic protein with a metabolic half-life of 16 hours in vivo, is a sensitive tumor marker. A serum level of β-hCG greater than 1 ng/mL strongly indicates pregnancy or the presence of a malignant tumor, such as endodermal sinus tumor, teratocarcinoma, choriocarcinoma, molar pregnancy, testicular embryonal carcinoma, or lung oat cell carcinoma.
Most glandular epithelial cells express the high-molecular-weight glycoprotein CA 15-3, which is encoded by the MUC-II gene. The assay’s main goal is to monitor patients who have had a mastectomy for breast cancer. CA 15-3 is positive in patients with a variety of disorders, including liver disease, autoimmune diseases, and other carcinomas. The absolute concentration of CA 15-3 is less predictive than the variation in it. Tumor marker concentrations change in response to changes in tumor load.
For detecting early recurrence of breast cancer, the CA 27.29 tumor marker may be useful in combination with other clinical methods. It is not recommended as a screening test for breast cancer. Increased levels of CA 27.29 (>38U/mL) in a woman with threatened breast carcinoma may suggest chronic disease and the need for additional testing or procedures.
Patients with pancreatic, hepatobiliary, colorectal, gastric, hepatocellular, pancreatic, and breast cancers have elevated CA 19-9 levels. Its primary use is as a diagnostic tool for colorectal and pancreatic cancer.
The CA 125 marker is elevated in ovarian and endometrial carcinomas, as well as benign disease in multiple organs such as pelvic inflammatory disease and endometriosis.
CEA plasma levels of more than 12ng/mL are closely linked to cancer. Endodermally derived gastrointestinal neoplasms, as well as neck and breast carcinomas, are commonly associated with elevated CEA levels. Additionally, CEA levels are elevated in 20% of smokers and 7% of former smokers.
CEA is used in clinical practice to monitor the growth of tumors in patients that have been diagnosed with cancer and have a high CEA level in their blood. A rise in CEA can suggest cancer recurrence if treatment results in a drop to normal levels (2.5ng/mL). A persistent elevation indicates the presence of underlying disease or a weak therapeutic response. The rate of clearance of CEA levels in patients who have had colon cancer resection surgery normally returns to normal within 1 month, but it can take up to 4 months. To detect a pattern, blood samples should be collected 2 to 4 weeks apart.
PSA is a prostate tissue-specific marker, not a prostate cancer marker. It’s a contentious diagnostic marker for prostate cancer. When normal glandular structure is compromised by benign or malignant tumor inflammation, PSA levels in the blood rise. As compared to benign hyperplasia, serum PSA is directly proportional to tumor volume, with a greater rise per unit volume of cancer. Free PSA can help differentiate between prostate cancer and benign prostatic hypertrophy. PSA levels tend to be useful in tracking the progression of prostate cancer and its reaction to treatment.
Miscellaneous Enzyme Markers
LDH levels are elevated in a wide range of cancers and other medical conditions. In solid tumors, the amount of LDH has been shown to correlate with tumor mass, so it can be used to monitor tumor progression.
Neuroblastoma, pheochromocytoma, oat cell carcinomas, medullary thyroid and C cell parathyroid carcinomas, and other neural crest–derived cancers have all been shown to contain neuron-specific enolase.
During pregnancy, ALP can be found in the placenta. Seminoma and ovarian cancer are two neoplastic diseases associated with it.
Miscellaneous Hormone Markers
Hormone serum levels that are too high or too low may act as tumor markers. Differentiated tumors of the endocrine organs and squamous cell lung tumors will secrete adrenocorticotropic hormone (ACTH, corticotropin), calcitonin, and catecholamines. β-hCG, ADH, serotonin, calcitonin, PTH (parathormone), and ACTH are all produced by oat cell carcinomas. These hormones may be used to monitor a patient’s treatment response.
Furthermore, progesterone and estradiol (estrogen) receptors are found in certain breast cancers, which are closely linked to a positive response to antihormone therapy. Catecholamine metabolites are secreted by patients with neuroblastomas and pheochromocytomas, which can be found in the urine. Neuroblastomas also produce neuron-specific enolase and ferritin, which are diagnostic and prognostic markers.
Breast, Ovarian, and Cervical Cancer Markers
Cancer antigens have been used to monitor treatment and assess cancer recurrence for more than a decade. Estrogen and progesterone receptors are widely recognized as prognostic and therapeutic decision-making markers. The use of the oncogene HER2/neu as a prognostic predictor and a marker linked to therapy choice is a relatively new method. With the advent of Herceptin, a chemotherapeutic agent that targets the HER2/neu receptor, this has been especially useful. Patients with breast cancer who express the oncogene HER2/neu have a worse prognosis, with shorter disease-free and overall survival than those that do not. Elevated serum levels of HER2 / neu associate with the presence of metastatic disease and indicate a poor prognosis, suggesting that HER2 / neu can be used to detect early recurrence. Combining HER2/neu serum measurements with other markers like CEA or CA 15-3 could increase recurrence detection sensitivity.