S-100 tumor marker: normal values ​​and reasons for increase


12/07/2017 Two stories prompted me to write an article about tumor markers.

1) Recently I received this very alarming message on the social network VKontakte:

“Hello, Dmitry Sergeevich! Tell me, please, I can’t calm down, I’m all on my nerves. The dermatologist found a suspicious spot on the temple and prescribed the s-100 tumor marker. It turned out to be enlarged quite strongly. During a visual examination, the oncologist did not see anything - what should I do? What to do next now? I just have two babies in my arms. Thank you for your answer, very grateful!”

2) I saw an advertising video on You Tube for a clinic in one of the cities with a million people. An oncologist (!!!) of the highest category (!!!) before removing a mole recommends taking S-100 and SCC tumor markers to “make sure that the mole being removed is benign.” And he does this not on the sly, so that no one except the patient hears, but on You Tube.

It's time to understand tumor markers - what they are, why they are needed and what real diagnostic value they represent.

Naturally, we will talk about tumor markers for malignant skin tumors.

Tumor marker levels are measured in a blood test

What is S-100?

S-100 is a protein, or rather a whole family of proteins that are involved in a wide variety of processes in the body. It is these that melanoma cells can release into the blood. And it is their level that can be measured, on the basis of which assumptions can be made about the diagnosis of melanoma.

Unfortunately, the level of this protein can be increased not only in melanoma, but also in other tumors - breast cancer, ovarian cancer, stomach cancer, prostate cancer and some others.

Another feature you need to know: S-100 levels can increase in rheumatoid arthritis, subarachnoid hemorrhage, acute myocardial ischemia, psoriasis, etc.

Tumor marker functions

The tumor marker received its name as a result of its ability to dissolve in ammonium sulfate at normal pH. The antigens of this tumor marker perform various functions and take part in various physiological processes.

The s100 level shows the presence or absence of melanoma, serves as an indicator of “breakdowns” in the central nervous system, and indicates various neoplastic diseases and inflammations. To diagnose brain damage, the forms of the protein are determined - tumor marker s100 (pp) or c100 (of). They are used as markers of possible damage to brain tissue due to circulatory disorders in the brain. In case of cerebral hemorrhages, the maximum concentration in the blood can be determined on the first day, in case of ischemic stroke - on the third day.

How valuable is S-100 in diagnosing melanoma?

There are at least two studies showing that the diagnostic yield of S-100 in diagnosing early stage melanoma is very low.

I'll tell you straight - none.

At stages I–II melanoma, the level of S-100 is increased in 1.3% of patients, at stage III – in 8.7%, and only at stage IV this protein increases in 73% of patients. In other words, even at stage IV melanoma, S-100 may not show that a person has this disease.

All authors note that the S-100 level as a diagnostic test does not have the necessary accuracy for diagnosing the early stages of melanoma.


Skin melanoma

When should I take the S-100 test (neuroendocrine tumors)?

  1. Diagnosis, staging, monitoring and evaluation of the effectiveness of melanoma therapy;
  2. Additional diagnosis of brain pathologies (hemorrhages, injuries, etc.);
  3. As part of the comprehensive detection of cardiac diseases accompanied by ischemic damage and heart failure;
  4. As an auxiliary test in patients with rheumatoid arthritis, systemic lupus erythematosus, psoriasis and other rheumatological pathologies.

What is SCCA (squamous cell carcinoma antigen)?

SCC antigen is a specific protein that can be secreted by squamous cell carcinoma cells of the mucous membranes and skin. Unfortunately, its diagnostic value has absolutely the same problem as the S-100.

According to studies, the level of SCC antigen increases in only 44% of patients with squamous cell carcinoma of the skin or mucous membranes. In addition, elevated SCC values ​​may also occur in psoriasis, eczema, atopic dermatitis, renal failure, tuberculosis, sarcoidosis, as well as cancer of the esophagus, lung, anal canal and vulva.

These facts suggest that SCC cannot and should not be used to diagnose the primary tumor in squamous cell skin cancer.


Squamous cell skin cancer

Combinations for testing for oncology

The antigen of this protein is a homo- and heterodimer of α or β in three combinations:

  • αα – in striated muscles, kidneys, heart, liver;
  • αβ – melanocytes;
  • ββ – in glial and Schwann cells.

The doctor himself determines the option required for the test. This blood test is performed to diagnose and monitor the outcome of treatment for cancer, neurological diseases and diseases of a neurological nature. s100 is the only tumor marker susceptible to melanoma. Testing for this antigen is also necessary if you have unfavorable heredity for types of cancer that can be detected by this tumor marker.

What real practical applications do S-100, LDH and SCCA have now?

All 3 markers listed can be used for three purposes:

1) Monitoring the progression of the disease - the development of metastases and relapses.

2) Monitoring the response to therapy.

In situations 1) and 2) it is important to know the levels of S-100 and LDH that were before treatment.

3) As individual prognostic factors. Moreover, in the case of melanoma, this is true more for LDH than for S-100. For SCC in squamous cell carcinoma of the skin and mucous membranes, this statement, to put it mildly, has not been proven .

References

  1. Clinical guidelines for melanoma of the skin and mucous membranes, 2018. - 94 p.
  2. Donato, R., Cannon, B., Sorci, G. et al. Functions of S100 proteins. - Curr Mol Med., 2013. - Vol. 13(1). — P. 24-57.
  3. Leclerc, E., Vetter, S.. The role of S100 proteins and their receptor RAGE in pancreatic cancer. - Biochim Biophys Acta., 2015. - Vol. 1852(12). — P. 2706-2711.
  4. Bresnick, A., Weber, D., Zimmer, D. S100 proteins in cancer. - Nat Rev Cancer, 2015. - Vol. 15(2). — P. 96-109.
  5. Palmer, S., Erickson, L., Ichetovkin, I. et al. Circulating serologic and molecular biomarkers in malignant melanoma. - Mayo Clin Proc., 2011. - Vol. 86(10). — P. 981-90.
  6. Rindi, G., Klimstra, D., Abedi-Ardekani, B. et al. A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal. - Mod Pathol, 2021. - Vol. 31. -P.

Which test is most accurate for diagnosing melanoma and skin cancer?

The most accurate diagnostic test for suspected melanoma and skin cancer is an excisional biopsy (complete removal) of the entire formation, including 1–3 mm of healthy skin, followed by histological examination. In some cases, it is possible to remove a fragment ( incisional biopsy ) of a suspicious formation, capturing the thickest part, also with histology.

Please note - this is not my opinion. This is the opinion of the major oncology associations NCCN and ESMO. There is not a word about any cytological examination of scrapings, punctures of moles or dermatoscopy in their practical recommendations - these are auxiliary preliminary tests.

Decoding the results

For such a study, cerebrospinal fluid is taken, sometimes cerebrospinal fluid or blood from a vein - in most cases. The normal level of protein is considered to be a concentration of no higher than 0.105 μg/l. If cerebrospinal fluid was collected, then the concentration considered normal will be no higher than 5 μg/l. If the level is higher, this is considered a pathology.

But almost 100% proof of a tumor process is a fivefold or more increase in the level of s100. If the indicators are higher than normal, but not very much, this may indicate diseases of another origin. But an accurate diagnosis is made on the basis of other tests, and not just this tumor marker. Therefore, the patient needs to undergo additional examinations.

Why can’t you donate tumor markers “just for prevention”?

Because the result of these tests, if prescribed unjustifiably, very often be unreliable. There are 2 options:

1) False positive result - the test says that there is cancer, but in fact it is not. The person begins to be frantically examined, nothing is found anywhere, and a real neurosis develops.

2) False negative - the test says that there is no cancer, but there is. It’s even worse here: instead of adequate examinations, a person calms down and grows the tumor until the later stages, when treatment is no longer effective.

Reduced Protein S‑100

  • effective treatment of the disease;
  • severe heart failure.

Attention to the Patient

  • the concept of norm is not absolute and has no clear boundaries
  • Normal reference values ​​often vary significantly among people of different sexes and age groups.

Remember that only your attending physician, who knows your medical history well, can provide a clear interpretation of the test results.

What to do if you have tested the tumor markers S-100, SCC and they are positive?

Unfortunately, you will need to undergo a fairly in-depth examination, otherwise you will most likely not be able to relax. A FULL examination of all skin by an oncologist-dermatologist is required, including dermatoscopy of all moles on the body, clinical and biochemical tests of blood, urine, ultrasound of the abdominal cavity and all groups of lymph nodes, pelvis, and chest x-ray.


If positive tumor markers are detected, a full diagnosis will be required

Features of preparation and analysis


Preparing for the procedure excludes eating in the last twelve hours, but you must drink water.
To determine the brain-specific protein, venous blood is taken from the elbow (3-5 ml), in the morning on an empty stomach using the puncture method. The sample is sent in a tube for electrochemiluminescent immunoassay. The patient is required to properly prepare:

  • Eat your last meal 4-6 hours before, ideally 8-12 hours before.
  • Before the analysis, drink only water (purified, without gas).
  • Avoid training for 4 days.
  • 30 minutes before sample collection, do not be nervous and do not smoke.

The selected biomaterial is subjected to centrifugation in the conditions of the laboratory that collected the sample. This step is necessary to remove clotting factors. The S100 tumor marker is calculated by the level of luminescence during the reaction of enzyme-labeled antibodies with a chemiluminescent substrate. The analysis is carried out for several hours, and the answer is usually given within a day, not including the day of taking the biomaterial, in units of measurement - μg/l (micrograms per liter).

Summary, or Briefly about the main thing

Tumor markers are useless in the primary diagnosis of melanoma and skin cancer.

Moreover, I strongly do not recommend taking them as the only method of examination, since with a false positive result, neurosis may develop. Tumor markers S-100, LDH and SCCA are currently used very limitedly in dermato-oncology .

Other articles:

  • Frequently asked questions: what you can and cannot do before and after mole removal
  • Shaving, hair removal and tattoos if you have moles
  • Why is it important to detect melanoma at an early stage?
  • Many moles on the body - how many?

Preparation

Melanoma tumor marker determination can be done in several ways. This is, first of all, a study of blood taken from a vein, a urine test, and also a study of the composition of the cerebrospinal fluid.

The first technique is one of the most popular and informative. Decoding the result takes no more than one day. However, if necessary, a repeat procedure may be prescribed. In this case, the conclusion will be ready within a few hours.

To obtain the most reliable information during a laboratory test, the patient must follow a number of preparatory recommendations.

First of all, you need to remember that the test is taken only in the morning on an empty stomach. For this reason, even a light breakfast and tea are not allowed. The last meal should also be taken at least eight hours before the test.

The evening before the procedure, it is necessary to avoid eating fatty and fried foods, carbonated, tonic and alcoholic drinks. In addition, it is advisable to give up alcohol a few days before the diagnostic event.

On the day when biological fluid is taken, you should not expose the body to physical stress or nervous stress.

Smoking is permitted no later than two hours before the test. It is better to give up cigarettes as soon as possible.

Lung tumor markers

Tumor markers of the lungs and bronchi are the names of certain enzymes that are produced during the formation of malignant tumors.

If any other procedures were prescribed on this date, they should be carried out only after taking blood fluid.

If the patient is taking medications, then this must be reported to the specialist.

If a positive result is detected, the test is re-administered.

If we are talking about a woman who will donate blood to determine the S-100 tumor marker, then there are also several special requirements. First of all, the study is not carried out during menstruation.

Only if all recommendations are followed will the analysis show the most reliable results.

The procedure itself consists of first introducing enzyme-labeled antibodies into a biomaterial sample. After this, a chemiluminescent substrate is added to it. When reacting with the enzyme, a certain glow is observed.

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It is on the basis of the intensity of this indicator that the level of S-100 protein content in the whey fluid is determined.

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