by Dr. Adele Visser
Introduction
Tumor markers represent a variety of cellular products and subunits, aimed at providing an accessible manner for early detection, prognostication and monitoring of malignant disease.
These vary from cellular surface antigens, cytoplasmic proteins and enzymes, hormones, oncofetal antigens, oncogens and receptors and may be present in the tumor itself or be altered qualitatively or quantitatively within the cancerous or precancerous state. It can be measured in tissues and fluids (mostly utilized by pathologists in diagnosis) or in serum.
Measurement in serum is mostly utilized by clinicians and will functionally be used for:
- Screening and early detection.
- Diagnostic confirmation.
- Prognosis and Prediction and monitoring of therapeutic response.
- Monitoring disease and recurrence.
| Table 1. The ideal tumor marker has certain characteristics (adapted from reference 1). | |
| Characteristics | Comments |
| Highly specific | Detectible only in one tumor type |
| Highly sensitive | Non-detectable in benign disease |
| Long lead-time | Sufficient time for alteration of natural disease course |
| Levels correlate with tumor burden | Prognostic and predictive utility |
| Short half-life | Useful in serial monitoring |
| Simple and cheap test | Applicable as screening test |
| Easily obtainable specimen | Acceptability by target population |
Current Validated use for Tumor Markers
However appealing this notion is, no single tumor marker has been developed that complies with these criteria and cross-reaction occurs in benign disease.
In an attempt to address these issues, various professional bodies have attempted to combine serum tumor markers with various procedures (mostly imaging) and redefining reference ranges in terms of change velocity and age, with some success, however not universally accepted at this point.
At present, tumor markers are largely validated for use in the monitoring of confirmed disease through the use of marker kinetics. For this to be of clinical value, these assays need to be performed using the same methods, preferably the same laboratory site.
| Table 2. Current use of serological tumor markers. | |||||
| Tumor Marker | Associated malignancies | Non-malignant Conditions (limited list) | Potential Clinical Uses | ||
| Primary | Secondary | Ectopic Production | |||
| Oncofetal antigens AFP CEA |
Primary HCC Colorectal carcinoma |
Teratoblastoma (ovary/testes) Various carcinomas |
GIT, renal, breast, bladder, ovarian carcinoma | Pregnancy Liver disease |
S,D,P,M P,M |
| Hormones βHCG Calcitonin Metanephrines Chromogranin A IGF-1 |
Choriocarcinoma Medullary carcinoma Pheochromocytoma Pheochromocytoma Neuroblastoma Pituitary cancer |
Testicular / trophoblastic tumors Cancer, liver, renal cancer Thyroid, liver, renal cancer Neuroblastoma / Ganglioneuroma MEN, small-cell lung, carcinoid Insulinoma |
Gastric, pancreas carcinoma Lung, islet cell, carcinoid, breast, ovary carcinoma Endocrine tumors |
Pregnancy Marijuana use Renal failure Use of PPI’s Dietary, drugs PPI’s |
D,P,M S,M,P D |
| Glycoproteins CA 15-3 CA 19-9 CA 72-4 CA 125 |
Breast cancer Pancreatic / gastric carcinomas Gastric carcinoma Ovarian carcinoma |
Various carcinomas Various carcinomas Various carcinomas Various carcinomas |
Cirrhosis / Granulomas GIT inflammation RA Breast, ovarian liver disease Reproductive cycles, GIT inflammation |
M,R P,M M,D,R |
|
| Isoenzymes PSA NSE |
Prostate carcinoma Small-cell lung carcinoma |
Neuroblastoma, kidney tumors | BPH PPI’s, haemolysis, renal failure |
S,M,D,P | |
| Cell components TAG 72 Immunoglobulins |
Gastric carcinoma Multiple myeloma |
Colorectal, lung, pancreas, ovarian cancers Gammopathies |
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M = monitoring R = Recurrences S = Screening P = Prognosis D = Diagnosis RT = Response to therapy
References
- Sharma S. 2009. Tumor markers in clinical practice: General principles and guidelines. In J Med Paediatr Oncol. 30(1):1-8