The problem of traditional diagnostics
Traditional morphological research methods have been and remain the baseline standard in oncopathology for decades. Their essence lies in the visual assessment of tissue and cellular structure under a light microscope. This classical approach demonstrates high diagnostic value when dealing with differentiated tumors and their metastases. In such clinical cases, tumor cells retain sufficient characteristic features of the tissue from which they originally arose. This allows the pathologist to confidently determine the source of tumor growth.
However, in real clinical practice, specialists regularly encounter poorly differentiated and undifferentiated malignant tumors. The cells of these aggressive neoplasms lose their initial specialization so profoundly during their development that visually establishing their tissue origin becomes completely impossible. It is precisely in this complex diagnostic situation that modern molecular-biological and high-tech morphological methods come to the rescue. They allow physicians to look deep inside the cell — at the ultrastructural and molecular-genetic levels.
Modern research methods
An entire arsenal of advanced laboratory technologies is used to identify the specific characteristics of a tumor cell. Each of the methods listed below solves its own narrow diagnostic task, and their skillful combination provides specialists with the most complete picture of the disease:
- Immunohistochemistry (IHC): one of the most important methods in modern pathology, allowing the detection of specific antigens directly in a histological tissue section.
- Polymerase chain reaction (PCR): a molecular biological method that repeatedly copies specific DNA segments, helping to identify minimal genetic alterations.
- In situ hybridization : a unique technology that makes it possible to detect specific nucleic acid sequences directly in cells or tissues while preserving their natural spatial arrangement.
- Blotting: a classical molecular method used for the precise separation and subsequent identification of specific proteins or nucleic acids.
- Cytogenetic analysis: a specialized study aimed at a detailed examination of chromosome structure and the identification of major structural rearrangements.
- Electron microscopy (EM): a morphological method providing tremendous magnification and allowing the visualization of the minutest details of cell ultrastructure.
Classification of tumor markers
Depending on which specific pathological process, structural element, or cellular mechanism a particular marker reflects, it is customary in modern pathology to distinguish six main classification groups:
- Cellular differentiation markers. Demonstrate which specific cell type the studied tumor strives to belong to, even if it appears completely undifferentiated outwardly.
- Histo- and cytogenetic markers. Directly indicate the tissue origin of the malignant neoplasm, helping to determine the primary site.
- Markers of chromosomal and genetic rearrangements. Reflect fundamental genetic mutations that underlie the malignant transformation of the cell.
- Markers of impaired cellular proliferation. Demonstrate the rate and degree of aggressiveness of tumor cell division, which is critically important for assessing the prognosis of the disease.
- Markers of cell death (apoptosis). Allow physicians to assess how successfully tumor cells are able to evade programmed cell death.
- Markers of invasion and metastasis. Characterize the ability of malignant cells to destroy surrounding healthy tissues, penetrate blood vessels, and form secondary foci.
Briefly: answers to topical questions
Which specific markers belong to the group of cellular differentiation markers?
Cellular differentiation markers indicated in the sources include:
- Neuronal markers — neuron-specific enolase, synaptophysin.
- Chromogranin — a marker of neuroendocrine differentiation.
- Hematopoietic cell markers — CD45 and other CD markers.
- Muscle differentiation markers — myogenin, desmin, actin.
- Mesenchymal differentiation marker — vimentin.
- Marker of primitive neuroectodermal tumors — CD99.
- S-100 protein — a marker of Schwann cell differentiation.
- Pancytokeratins — expressed in small cell lung cancer.
Which marker proteins are used to assess cell death and apoptosis?
The sources indicate the following proteins involved in the assessment of cell death and apoptosis:
- Initiator caspases — caspase 8 and caspase 9.
- Executioner caspases — caspase 3, as well as caspase 6 and 7.
- Adaptor proteins — FADD and Apaf-1.
- Pro-apoptotic proteins — p53, Bax, and Bak.
- Anti-apoptotic protein — Bcl-2.
- Targets of executioner caspases — Rb, PARP, and CAD.
- CD107 (LAMP) — a marker of degranulation of cytotoxic T lymphocytes and NK cells.
Which specific proliferation markers are used to assess the aggressiveness of tumor cell division?
To assess the proliferative activity of tumor cells, the marker protein Ki-67 is used, which is detected by immunohistochemistry. Mitosis counting (mitotic index) is also used. In adrenocortical carcinoma, Ki-67 is indicated as a reliable negative prognostic indicator, and in breast cancer, the presence of Ki-67 defines a subgroup with high proliferative activity.
To memorize the 6 groups of markers, use the phrase: "Differentiated Genetics Rewires Proliferation, Apoptosis, and Metastasis" (Differentiation, Histo/cytogenetic, Rearrangements, Proliferation, Apoptosis, Metastasis).
Class and exam questions
In what cases does traditional morphology fail in diagnostics?
Traditional methods lose their effectiveness when studying poorly differentiated and undifferentiated malignant tumors, as their cells completely lose the features of the original tissue.
What methods are used to diagnose undifferentiated tumors?
For such neoplasms, molecular-biological and modern morphological methods (PCR, in situ hybridization, immunohistochemistry, electron microscopy) are used, allowing the evaluation of changes at the ultrastructural and molecular-genetic levels.
What does in situ hybridization allow us to see?
This method allows the detection of specific nucleic acid sequences directly in the cell or tissue while preserving their natural spatial arrangement.
What else to study on this topic
- Principles of polymerase chain reaction (PCR) in oncopathology.
- The technique of in situ hybridization and its clinical significance.
- The role of immunohistochemistry (IHC) in verifying the tissue origin of a tumor.
- Ultrastructural signs of malignancy in electron microscopy.
- Mechanisms of cell death and apoptosis markers.
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