Immunohistochemistry in Oncology

The Role of Morphology in Tumor Diagnosis

The classification of any oncological disease is based on clinical, molecular-genetic, and morphological data. The latter group (which includes IHC) is considered fundamental for final diagnostic verification and risk stratification.

In addition to immunohistochemistry, the modern laboratory arsenal includes electron microscopy, blot analysis, in situ hybridization, cytogenetic analysis, and flow cytometry (the latter is especially important for monitoring remission). However, it is IHC that allows for the visual assessment of mutant protein localization directly within the tissue. For example, in the case of a TP53 gene mutation, the p53 protein changes conformation and accumulates in cell nuclei, which is easily detected by immunohistochemical methods.

Classification of Molecular Markers

Molecules detected in tissues and biological substances reflect different aspects of tumor biology. Markers of cellular differentiation, genetic rearrangements, invasion, disrupted proliferation, and cell death are distinguished.

In oncological practice, the following IHC markers have been studied in the greatest detail:

• Cell proliferation: Ki-67 marker.
• Differentiation: epidermal growth factor receptor HER-2.
• Apoptosis (cell death): Bcl-2 and survivin proteins.
• Cell adhesion: E-cadherin and CD24 molecules.
• Angiogenesis (blood vessel growth): HIF-1α factor and matrix metalloproteinases.
• Mitosis: Aurora A kinase.
• C-met (MET) protein and markers of vascular invasion.

Determining Microsatellite Instability (MSI)

Assessment of microsatellite instability status (especially identifying MSI-H status) plays a key role in confirming hereditary pathologies such as Lynch syndrome.

Historically, colorectal cancer was evaluated using PCR with a panel of 5 mononucleotide markers (short tandem repeats). However, for tumors of other localizations, including urothelial carcinomas, this standard method has insufficient sensitivity. Therefore, IHC analysis is recommended in such cases.

The goal of the study is to demonstrate the loss of expression of specific DNA mismatch repair (MMR) system proteins. These include MLH1, MSH2, MSH6, and PMS2.

If IHC confirms MSI-H status, the patient is referred for high-throughput sequencing (NGS, MMR gene panel) to search for germline mutations.

Risk Stratification and Response Predictors

Immunohistochemistry is actively used to predict tumor aggressiveness. Risk stratification markers include:

1. p53 — aberrant staining is taken into account (global loss of expression or overexpression).
2. Beta-catenin — its nuclear expression has diagnostic significance.
3. MMR proteins — used to screen for neoplasms associated with Lynch syndrome.
4. PD-1 and PD-L1 — expression of these molecules has high prognostic value in poorly differentiated upper tract urothelial carcinoma.

It is important to remember that some potential treatment response predictors (such as RRM1 and CYP2W1) are not yet validated for daily clinical practice due to study limitations (small sample sizes, retrospective design).

Class and exam questions

What else to study on this topic

• Genetic Testing in Oncology: NGS and Multigene Panels
• Lynch Syndrome: Diagnostic Criteria and Management Tactics
• ACMG Classification of Pathogenic Variants
• Molecular Mechanisms of Carcinogenesis and the Role of the p53 Gene
• Mechanisms of Apoptosis: Bcl-2, Survivin, and Their Role in Tumor Survival

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.