The main criteria that must be met by a specific protein to be considered a true tumor marker are represented by:
- High specificity – the marker should not be detected in healthy people or those who associate diseases with benign evolution
- Increased sensitivity – the marker must show increased serum concentrations from the early stages of the tumor’s evolution
- Organ specificity
- The good correlation with the stage of evolution of the tumor process and its dimensions
- High correlation with the prognosis of the disease
- Highly predictive value.
These criteria are not fully met by any tumor marker known to date, which is the main reason why it is necessary to corroborate the laboratory results with those of other investigations such as biopsies and imaging tests to establish the diagnosis of cancer.
Tumor markers are useful both for establishing the diagnosis of primary tumors and for detecting residual cancers in patients who have undergone oncological surgery or have completed other types of antitumor therapies (chemotherapy, radiotherapy, targeted therapy, immunotherapy).
In the presence of the patient’s clinical manifestations that raise the suspicion of a neoplastic pathology, the specialist doctor can recommend the determination of certain types of tumor markers in accordance with the patient’s symptoms. The prostate-specific antigen PSA, prostatic acid phosphatase and thyroglobulin represent the tumor markers with the highest organ specificity.
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Types of tumor markers
Depending on the site of synthesis and the expressed characteristics, tumor markers can be classified as follows:
- Oncofetal and oncoplacental antigens such as carcinoembryonic antigen CEA, alpha fetoprotein AFP and human chorionic gonadotropin HCG.
- Carbohydrate molecules with known epitopes (specific binding sites for antibodies) by monoclonal antibodies of the type CA 19-9, CA 125, CA 15-3.
- Antigens for the determination of differentiation and proliferation – prostate-specific antigen PSA, neuron-specific enolase NSE, beta 2 microglobulin.
- Hormones with ectopic synthesis ACTH in lung neoplasm, calcitonin in thyroid neoplasm.
- Proteins with ectopic synthesis, monoclonal immunoglobulins and Bence Jones proteins in multiple myeloma.
Another classification of tumor markers is made according to the location of these proteins in the body as follows:
- Circulating tumor biomarkers they can be determined from the patient’s blood, urine, stool sample, hematogenous marrow or saliva.
- Biomarkers of tumor tissue or tumor cells which requires a biopsy – the more frequently determined tumor tissue markers are represented by the estrogen and progesterone receptor and the FGFR3 gene mutation.
When does the doctor recommend testing tumor markers?
The main indications for the determination of tumor markers are represented by:
- Early diagnosis of tumor pathologies in patients who associate increased risk factors for this type of disease – hereditary-collateral or personal antecedents of tumors or other chronic diseases with increased risk of malignancy, liver cirrhosis, intestinal polyps.
- Dynamic monitoring of the patient’s evolution in the post-therapeutic stages – after the completion of the oncological therapy, the tumor markers must decrease significantly or register values below the detection limit.
- Staging and establishing the prognosis in the case of patients who associate evolving tumor pathologies – the serum concentration of the tumor marker varies directly proportional to the degree of evolution of the tumor and its extent.
- Evaluation and monitoring of the therapeutic response after the initiation of oncological treatment or the practice of surgical excision of the primary tumor – the significant decrease in the level of the tumor marker after the surgical cure of the primary tumor and/or the completion of the oncological therapy presents an indicator that attests to the favorable evolution of the patient.
- Early detection of residual tumor disease and tumor recurrence – the partial removal of cancer cells during surgery favors the appearance of residual oncological disease that can be detected through the persistence of tumor markers. The decrease of tumor markers followed by their increase at a certain variable time interval means the recurrence of the tumor pathology.
- Orientation of the therapeutic plan depending on the expression or absence of certain tumor markers that indicate the susceptibility of the tumor tissue to certain types of therapies.
It is worth mentioning that tumor markers are not indicated as a screening method at the level of the asymptomatic general population because their organ specificity is much too low to provide predictive value to this investigation.
Tumor markers frequently used in medical practice
Tumor markers commonly used in medical practice to confirm tumor pathologies located in different systems and organs of the body are represented by:
- Alpha-Feto Protein (AFP) used to confirm the suspicion of hepatocellular cancer in the case of cirrhosis in late stages of evolution and ovarian, testicular or extragonadal germ cell tumors.
- CA 19-9 it is recommended for the diagnosis and monitoring of pancreatic adenocarcinomas, malignant tumors of the bile ducts, ovary, colon and rectum.
- CA 125 – recommended for the diagnosis and evaluation of the prognosis in the case of ovarian cancer. This marker does not show organ specificity because it can also grow in pancreatic, endometrial and fallopian tube cancer, but it can differentiate between a benign pelvic tumor mass and a malignant ovarian pathology.
- CA 72-4 it is a marker used by the first intention to monitor the therapeutic response and the evolution of patients diagnosed with gastric tumors, but it can also be used as a secondary marker for mucinous ovarian tumors.
- CA 15-3 it is recommended for post-therapeutic monitoring of breast cancer.
- Calcitonin indicated for the screening of people with a heredo-collateral history of medullary thyroid cancer and establishing the differential diagnosis of malignant thyroid tumors with “cold” thyroid nodules.
- CEA or carcinoembryonic antigen recommended for monitoring the therapeutic response of patients with malignant tumors of the colon and rectum, breast, lung, gastric, pancreatic and ovarian cancer.
- DIGITAL 21-1 used to confirm the diagnosis of lung cancer and establish its differential diagnosis with lung formations of unknown origin. This tumor marker is also useful for monitoring the evolution of patients with bladder tumors.
- HCG total recommended for the diagnosis and monitoring of the therapeutic response in trophoblastic and gestational disease (hydatidiform mole, choriocarcinoma) and testicular and extragonadal germinal tumors.
- NSE Enolaza Neuron Specific – indicated for monitoring the therapeutic response and evolution of small cell lung cancers.
- HER-2 represents an oncogene that encodes a protein with the role of a receptor for certain cell growth factors, used to guide the management of breast, ovarian, bladder, stomach and pancreatic cancer.
Other conditions in which tumor marker testing can be recommended
There are also situations in which tumor markers can record increased serum values outside of tumor pathologies, this being one of the reasons why the oncological diagnosis must also be supported by the patient’s clinical manifestations and the results of imaging investigations.
Benign conditions that can cause an increase in the serum concentration of certain tumor markers they are represented by:
- Hepatitis, cirrhosis due to drug toxicity, inflammatory bowel disease in the case AFP.
- Amyloidosis can generate increases in Bence-Jones proteins and monoclonal immunoglobulins.
- Renal diseases and hepatitis can cause increases in beta 2 microglobulinei.
- Infections in the urinary tract can associate increases of bladder tumor antigen.
- Cirrhosis, hepatitis, systemic lupus erythematosus, tuberculosis, non-cancerous breast lesions can be accompanied by increased values of CA 15-3.
- Pancreatitis, ulcerative colitis, inflammatory bowel disease, biliary obstruction, thyroid disease and rheumatoid arthritis can develop with increased levels of CA 19-9.
- Endometriosis, ovarian cysts, pelvic inflammatory disease, pancreatitis, cirrhosis, hepatitis, pleural effusions can promote growth CA 125.
- Ovarian cysts, liver, kidney and non-tumoral breast pathologies can be accompanied by elevated concentrations of CA 27-9.
- Chronic renal failure can favor the increase of values calcitonin.
- Pancreatitis, hepatitis, cirrhosis, biliary obstruction, pelvic inflammatory disease, hypothyroidism and peptic ulcer can associate increases in CEA.
- Hemolytic anemia, liver failure, chronic kidney disease in the late stages of evolution, brain injuries, stroke and epilepsy can increase NSE values.
Studies are currently underway on the structure, function and expression pattern of certain specific tumor proteins as well as their interaction with other cells in the body, with the aim of discovering new highly specific and sensitive methods for the early diagnosis of tumors.
References:
- Serum Tumor MarkersGreg L. Perkins, Evan D. Slater, Georganne K. Sanders, John G. Prichard
- Tumor markers: A diagnostic toolMadhav Nagpal, Shreya Singh, Pranshu Singh, Pallavi Chauhan, Meesam Abbas Zaidi
- Tumor markers in clinical practice: General principles and guidelinesS. Sharma
2023-12-27 23:10:55
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