S-100 Proteins

S-100 proteins are small calcium-binding proteins belonging to the same family as chaperonins and troponin C. Currently, approximately 25 different S-100 proteins have been identified. They perform various functions in the human body, including cell growth and differentiation, transcription, protein phosphorylation, secretion, muscle fiber contraction, and other processes. They also regulate the cell cycle and apoptosis, which means they can participate in oncogenesis. The concentration of S-100 proteins varies in many malignant tumors, a feature that can be used for tumor diagnosis and prognosis.

S-100B in Melanoma
The S-100B protein holds the greatest diagnostic value in melanoma. S-100B is a standard immunohistochemical marker commonly used in the pathological diagnosis of melanoma. It is also secreted into the bloodstream, where its levels can be measured in malignant melanocytes. Currently, S-100B is the most studied biomarker for melanoma, and its levels correlate well with the clinical stage of the disease. Consequently, the highest concentrations of this biomarker are observed in disseminated tumors. In healthy individuals and in patients with benign skin lesions, S-100B levels are within normal limits; however, they are elevated in 1.3%, 8.7%, and 73.9% of melanoma cases at stages I/II, III, and IV, respectively. Given that elevated levels of S-100B are rarely found in early melanoma, this biomarker is not used for melanoma screening. Instead, S-100B is utilized for prognostic assessment, as increased levels are associated with a more aggressive disease course.

Other S-100 Proteins in Oncology
Other members of the S-100 family can also have clinical significance in the diagnosis of various cancers. For example:

• S-100A4 can be used for prognostic evaluation of breast, stomach, bladder, pancreatic, and lung cancers.
• S-100A7 serves as a biomarker for lung and ovarian cancers.
• S-100A9 may be useful in the differential diagnosis between prostate cancer and benign prostatic hyperplasia.

S-100 proteins have also been demonstrated to be valuable in diagnosing non-malignant pathologies.

S-100B in the Central Nervous System
In the brain, S-100B is predominantly produced by astrocytes. An increase in S-100B synthesis indicates astrocyte activation in response to neural tissue damage, particularly in the context of hypoxia or hypoglycemia. Elevated levels of S-100B in blood and cerebrospinal fluid are observed in cases of traumatic brain injury. In newborns, high levels of this biomarker can indicate hypoxemic/ischemic encephalopathy due to neonatal asphyxia. Additionally, S-100B levels are elevated in patients with systemic lupus erythematosus with central nervous system involvement.

S-100A1 in the Myocardium
The synthesis of S-100A1 is characteristic of the myocardium, where it plays a role in myofibril contraction. S-100A1 synthesis increases in cases of right ventricular hypertrophy and decreases in severe heart failure. Elevated blood levels of S-100A1 are observed in patients with acute myocardial infarction. Studies have shown that 48–72 hours after a cardiovascular event, patients may present with a Glasgow Coma Scale score below 6, neuron-specific enolase (NSE) levels above 65 ng/ml, and S-100 protein levels exceeding 1.5 µg/l.