How and why tumor staging is performed
The staging of a malignant process is based on four key criteria: the true size of the neoplasm, the degree of involvement of surrounding tissues, regional lymph node involvement, and the presence of distant metastases.
This information is critically important for two tasks:
- Determining prognosis. While the probability of a favorable outcome is high at stage I, the prognosis progressively worsens at subsequent stages.
- Developing treatment tactics. Staging helps select optimal therapy methods, their combination, and the correct sequence of local and systemic effects on the body.
In global oncological practice, the TNM system is the standard for describing the anatomical extent of the disease:
- T (Tumor) — characterizes the tumor itself, its size, and depth of tissue invasion.
- N (Node) — indicates whether regional lymph nodes are involved.
- M (Metastasis) — records the presence and extent of distant metastases.
What are tumor markers
Tumor markers (or clusters of differentiation, CD — cluster of differentiation) are specific surface or cytoplasmic antigens of a glycoprotein or glycolipid nature. During malignant growth, the number of such differentiation antigens multiplies significantly.
In clinical practice, markers serve as a crucial supplement to classical histology. They help physicians identify high-risk groups, monitor therapy efficacy, and predict potential relapses.
Several groups of markers are distinguished:
- Specific cellular markers. Malignant cells often retain the ability to produce substances characteristic of their normal precursors. For example, prostate adenocarcinoma exhibits high activity of prostate-specific acid phosphatase and expression of PSA (prostate-specific antigen).
- Fetal antigens (embryonic and fetal Ag). The tumor may synthesize compounds that are normally produced only during ontogenesis. These include alpha-fetoprotein (detected in hepatocellular carcinoma, teratoblastoma, and pediatric hepatoblastoma) and carcinoembryonic antigen (characteristic of gastrointestinal tract cancer).
Special mention should be made of markers for neuroblastoma (a tumor of embryonic origin). It typically expresses Phox2b and C-kit (neural crest stem cell antigens), Sox10 and AP2α (immature glial cell markers), as well as NSE (neuron-specific enolase, an intracellular enzyme of cerebral neurons).
Cytoskeleton and tracking occult metastases
One of the most accurate methods of modern diagnostics is the detection of cytoskeletal markers. This involves using monoclonal antibodies against intermediate filaments of cells, allowing the origin of the tumor to be determined unmistakably:
- Keratins act as markers of epithelial cells and are therefore always preserved in carcinomas.
- Vimentin is a marker of mesenchymal origin cells, actively expressed in sarcomas. Important nuance: if antibodies to vimentin are detected in a carcinoma, they are localized exclusively in the stroma (blood vessel walls) rather than in the tumor tissue itself.
The problem of occult primary tumor. In clinical practice, 2% to 10% of patients face a situation where metastases are already detected, but the primary focus cannot be found. Moreover, in 15–20% of such cases, the source is not found even upon autopsy.
The solution to this problem is immunophenotyping of cells obtained from metastases. Enzyme-linked immunosorbent assay (ELISA) serves as the primary identification method here, accurately establishing the tissue origin of the metastasis and allowing appropriate therapy to be selected even if the primary tumor remains invisible.
Briefly: answers to topical questions
In which malignant neoplasms is alpha-fetoprotein detected?
Alpha-fetoprotein is listed in sources as a tumor marker for the following tumors:
- Hepatocellular carcinoma.
- Hepatoblastoma in children.
- Teratoblastoma.
- In germ cell tumors of the ovary: yolk sac tumor; elevated AFP is also noted in embryonal carcinoma, polyembryoma, and immature teratomas.
- In mediastinal tumors, AFP is part of the specific marker panel for germ cell tumors; elevated markers suggest non-seminomatous germ cell tumors.
- In biliary tract cancer, AFP is included in the mandatory tumor marker list for laboratory diagnostics.
What fetal antigens act as tumor markers?
Fetal antigens, or embryonic and fetal antigens, are substances expressed by tumors that are normally synthesized only during fetal ontogenesis. Sources cite:
- Alpha-fetoprotein — hepatocellular carcinoma, teratoblastoma, hepatoblastoma in children.
- Carcinoembryonic antigen — GI cancer.
- PSA (prostate-specific antigen) — prostate cancer; specific antigen of prostate cells.
What does parameter G mean in an oncological diagnosis?
Parameter G (Grade) denotes the histological grading of a tumor, reflecting the degree of cellular differentiation. This criterion is assessed based on the histological structure of the neoplasm:
- Gx — grade cannot be assessed (insufficient data).
- G1 — well-differentiated (low grade).
- G2 — moderately differentiated (intermediate grade).
- G3 — poorly differentiated (high grade).
What is the Ki-67 proliferative activity index used for?
The Ki-67 index is listed in sources as a proliferation marker. It is used or considered in the following situations:
- In breast cancer, Ki67 serves as a proliferation marker; luminal A and B subtypes are distinguished based on the rate of cellular proliferation, and the presence of Ki67 defines the high-proliferation subgroup for which chemotherapy is most effective.
- In gastrointestinal neuroendocrine neoplasms following R0 resection, further tactics depend on Grade and Ki67: for G3 with Ki67 ≤ 55%, observation or chemotherapy is possible; for G3 with Ki67 > 55% or NEC, chemotherapy is indicated.
- In adrenal pathology, Ki67 is indicated as a reliable negative prognostic indicator and is included in the Helsinki score to predict metastatic potential.
- In biliary adenoma, a low proliferation index of Ki67 < 10% is indicated as a marker.
The abbreviation TNM is easily deciphered by the first letters of English words: T — Tumor itself, N — Node (lymph node), M — Metastasis (distant spread).
Class and exam questions
Why are tumor markers needed if histological examination is available?
Markers complement histology. They are essential for monitoring treatment efficacy, predicting relapses, and identifying high-risk groups.
Why do fetal antigens appear in gastrointestinal or liver cancer?
Malignant cells can revert to an embryonic type of synthesis, beginning to produce fetal antigens that are normally formed only during ontogenesis (e.g., alpha-fetoprotein or carcinoembryonic antigen).
How to distinguish carcinoma from sarcoma using markers?
Monoclonal antibodies against intermediate filaments are used. Carcinomas (epithelial tumors) express keratins, while sarcomas (mesenchymal tumors) express vimentin.
What else to study on this topic
- Mechanisms of embryonic antigen expression in mature tissues
- Enzyme-linked immunosorbent assay: principles for identifying the tissue origin of metastases
- Characteristics of neuroblastoma markers: from stem cells to immature glia
- Differential diagnosis of tumors of unknown primary origin
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