S100 protein tumormarker
For the first time S100 proteins were extracted by B. Moore in 1965 from the brain of a bull as unfractionated mixture, and got its name because of its ability to dissolve in 100% ammonium sulphate solution. Their concentration in the brain is 100,000 times higher than its content in other tissues and is up to 90% of soluble fractions of proteins of nerve cells.
Biochemistry of S100 protein
S100 protein is a small dimeric protein, i.e. consisting of two subunits that have a molecular mass of about 10.5 kDa each. S100 protein has a molecular mass of 21 kDa (10,5 kDa +10,5 kDa), belongs to the family of intracellular Ca-binding proteins (calcium binding proteins). S100 protein is a homo- and heterodimer consisting of two subunits (β or α) in various combinations: αα (S-100a), αβ (S-100 ab) и ββ (S-100b).
Currently identified at least 25 different proteins of this family: the S100A1 — S100A18, trichohylin, fillagrin, repetin, S100B, S100G, S100P, S100Z. Most S100 proteins (up to 85-90% of total content in the nervous tissue) are concentrated in astrocytes; 10-15% are located in the neurons, the minimum number of points is determined in oligodendrocytes.
S100 proteins are synthesized by glial cells and then transported into neurons. In the cell they are localized mainly in the cytoplasm and in the synaptic membrane and the chromatin. S100 A1 and S100 B is also expressed in melanoma cells. S100 proteins also found in muscle tissue cells, in the tissues of internal organs (liver, kidneys, etc.).
Function of S100 protein
Various forms of S100 proteins represent the most versatile of known macromolecules that are involved in the regulation of almost all major membrane, cytoplasmic and nuclear metabolic processes associated with provision of mechanisms for the perception and integration of incoming information in the nervous system, involved in the response genes early response, in the realization of genetic programs of apoptosis and antiapoptosis protection.
Representatives of the S100 proteins show tissue specific expressed and cleocinonline expression. They are involved in various processes – contraction, motility, cell growth and differentiation, cell cycle progression, transcription, cellular organization and membrane dynamics of the cytoskeleton, cells protection against oxidative damage, phosphorylation, secretion.
It is shown that S100Β exhibits neurotrophic activity at physiological concentrations and neurotoxic at high concentrations.
Experimentally proved that S100 group of proteins involved in the regulation of directional growth processes of neurons in the completion neuroontogenesis both morphologically and functionally, in the development of the main forms of innate behavior, the mechanisms of memory and learning. Numerous studies have proven the connection S100 protein with the development of anxiety disorders.
Clinical significance of S100 protein
Clinical interest in the S100 protein is associated with the use of it as a marker of brain damage in the following pathological conditions:
- Traumatic brain injury
- Alzheimer's disease (S100Β released from necrotic tissue may exacerbate neurodegeneration by S100Β-induced apoptosis)
- Subarachnoid hemorrhage
- Ischemic stroke and other neurological disorders
- Monitoring, assessing treatment efficacy, early detection of recurrences in malignant melanoma and other neoplastic diseases
- Perinatal hypoxic CNS lesions in children
- Inflammatory diseases
S100 protein - brain damage marker
Determine the level of S100 protein can be used as an additional tool to clinical data and results of instrumental studies in the management of patients with possible brain damage (stroke, trauma, tumor, etc.). The S100 concentration depends on the degree of brain injury and provides important information about the management and treatment of patients with cerebral disorders.
In case of injury S100 protein released from damaged brain cells into the systemic circulation, and can be determined in the blood within a few minutes after the injury.
S100 levels in such situations may be used to exclude light traumatic brain injury with high sensitivity (98.8%) and specificity (99.7%).
S100 protein values below 0.105 µg/l to minimize the probability of intracranial lesions and correlate with negative CT brain scan. The increase of S100 level after spontaneous subarachnoid hemorrhage correlates with the severity of pathology (level above 0.3 mg/l is associated with unfavorable course).
S100 protein concentration in the blood increased after the development of hemorrhagic or ischemic stroke in a straight line depending on the size of the brain lesion. Level of growth of S100 protein correlates with the severity of clinical symptoms of stroke. Also, monitoring of the concentration dynamics of S100 protein after stroke enables monitoring of repeated attacks.
Thus, the measurement of S100 protein in patients with stroke gives an accurate and objective assessment of the severity of the attack and the prognosis of the disease.
S100 protein is also secreted in tumors of brain tissue: gliomas and neuroblastoma. In the diagnosis of brain tumors determination of S100 protein must be supplemented by a determination of the NSE marker (neuron-specific enolase).
Also S100 protein can be used in the monitoring of patients with various disorders of the circulation — evaluation of the degree of destruction of brain tissue during short stops of the heart (level of S100 in these situations should return to normal within 24 hours) in patients with cerebrovascular disorders and in cases of extracorporeal circulation.
S100 protein — tumor marker associated with malignant melanoma
Malignant melanoma represents one of the most aggressive types of skin cancer. The tumor develops from melanocytes — cells that produce melanin (pigment). These cell produce S100 protein, which is used as a marker for malignant transformation of melanocytes.
For the favorable prognosis of this disease is critical for early diagnosis of the primary tumor. It is also extremely important and early detection of metastases and recurrences of the disease.
S100 is the only sensitive serological marker of melanoma. With adequate therapy and successful surgical intervention the content of this protein decreases. In patients suffering from malignant melanoma, particularly in stage II, III and IV, the elevated levels of S100 in the blood may characterize the progression of the disease. This is an important fact in monitoring these patients and the prognosis of disease.
Interpretation of results
Measurement of the concentration of S100 may vary considerably depending on the test procedure, the results obtained by different methods cannot be directly compared with each other, this can cause incorrect interpretation. If necessary, change testing procedures S100 during serial monitoring of the comparability of the results needs to be confirmed by parallel measurement of the two methods.
Units for the Elecsys S100 (Roche): mcg/l Reference values: < 0,105 µg/l (95% of healthy people without an overt manifestation of any pathology).
Increasing concentrations of S100 protein values contribute to the following conditions:
- Oncology — malignant melanoma (correlated with the stage of disease)
- Neurological disorders:
- metabolic brain damage
- traumatic brain injury
- spontaneous subarachnoid hemorrhage
- Alzheimer's disease
- ischemic stroke
- multiple sclerosis (level fluctuations)
- systemic lupus erythematosus (neuropsychiatric involvement — organic brain syndrome, convulsions, vascular incidents, psychosis)
- hepatic encephalopathy
- bipolar disorder during exacerbations but not during remissions
- neurological impairment after cardiac arrest and subsequent resuscitation
- Physiological conditions — intense physical exercise