Brief Overview of the Important Role of Immunohistochemistry

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6 2 月, 2026

On 6 2 月, 2026

Editor’s Note:

As the saying goes: “Money is not everything, but without money, nothing can be done.” Applied to pathological diagnosis, it can be said: “Immunohistochemistry is not everything, but without immunohistochemistry, nothing can be done.”

Nowadays, immunohistochemistry is basically popularized in municipal hospitals, but the scope of application, or the types of immunohistochemical antibodies used, still vary greatly. The important role of immunohistochemistry has not yet received sufficient understanding and attention. Some people even believe that immunohistochemistry is optional, or try to order it as little as possible or not at all due to other reasons. Therefore, this article will review the important roles of immunohistochemistry once again.

Determining Cell Type

Antibodies prepared using specific components within cells can label corresponding antigenic components within the cells to determine cell type. For example, keratin is a unique component of epithelial cells and can serve as a broad-spectrum marker for various epithelia; thyroglobulin is a specific component of thyroid follicular epithelium, prostate-specific antigen is only found in prostate epithelium, and synaptophysin is used to identify neurons and neuroendocrine cells.

Identifying Cell Products

Antibodies prepared using certain cell products as antigens can serve as specific markers for the corresponding products. For example, various hormones produced by endocrine cells can mostly be labeled using immunohistochemical techniques, such as calcitonin, a hormone secreted by thyroid parafollicular cells, which can be used for the diagnosis of medullary thyroid carcinoma. Alpha-fetoprotein produced by liver cancer cells can be used for the diagnosis of hepatocellular carcinoma.

Understanding Differentiation Degree

Most markers have specific distribution sites. For example, epithelial membrane antigen (EMA) stains on the cell membrane, but in poorly differentiated carcinomas, the cytoplasm of cancer cells can also be positive; the content of keratin is also related to the degree of differentiation, with less keratin content and weaker staining in poorly differentiated or undifferentiated carcinomas. Epithelial cells undergoing mesenchymal transformation may express the mesenchymal marker vimentin, while the expression of keratin and E-cadherin decreases.

Identifying Lesion Nature

When reactive hyperplasia of lymph nodes is difficult to distinguish from malignant lymphoma, T and B cell markers can be used to observe their quantity and distribution. If the lymph node structure is destroyed and a single type of cell proliferates diffusely, lymphoma can be considered, and T-cell or B-cell types can be distinguished accordingly. If epithelial cell dysplasia breaks through the basement membrane or destroys myoepithelial cells, invasive carcinoma is considered. The presence or absence of breast myoepithelial cells is important for distinguishing invasive breast cancer from ductal carcinoma in situ.

Confirming Spread Range

Early lymph node metastasis of certain cancers is sometimes difficult to distinguish from histiocyte hyperplasia in lymph sinuses. Epithelial markers and histiocyte markers can be used to differentiate them. Capsular and/or vascular or nerve invasion for the diagnosis of thyroid cancer and cholangiocarcinoma sometimes also relies on immunohistochemistry for confirmation.

Finding Primary Lesion

For metastatic tumors, immunohistochemistry can also be used to find the primary site. For example, if prostate-specific antigen is positive in metastatic carcinoma in bone tissue, it suggests it originates from the prostate. Tumors with unusual morphology in the liver and lungs may be metastatic, and immunohistochemistry can also be used for tracing, such as lung metastasis from renal clear cell carcinoma.

Identifying Special Cells

Some cells, such as Langerhans cells and melanocytes in the epidermis, dendritic cells in lymph nodes, and thyroid parafollicular cells, are difficult to distinguish under light microscopy. However, corresponding immunohistochemical markers like S-100 protein can clearly display their morphology and can be used for the diagnosis of these tumors.

Exploring Tumor Origin

Some tumors of unknown origin can be identified through immunohistochemistry, achieving consensus. For example, granular cell myoblastoma was once considered myogenic, but this tumor is negative for myogenic markers and positive for neural markers, proving it is of neural origin. Poorly differentiated spindle cell tumors may originate from epithelial, myogenic, or neural sources; round cell tumors may be of neural, lymphoid, or mesenchymal origin. Their origin can be determined by testing multiple markers.

Finding Infection Cause

For infectious diseases, specific antibodies can also be used to find the source of infection. For example, antibodies against cytomegalovirus (CMV), human papillomavirus (HPV), hepatitis B virus (HBV) surface antigen or core antigen, Epstein-Barr virus (latent membrane protein 1), and Toxoplasma gondii can be labeled separately. Commercial markers are now available to help diagnose the etiology of inflammatory lesions. The S protein antibody of the novel coronavirus can also be used for diagnosis and research.

Guiding Clinical Treatment

It is now confirmed that breast cancer, endometrial cancer, etc., are hormone-dependent and respond well to endocrine therapy. Estrogen receptor and progesterone receptor have become routine detection indicators for these tumors to guide treatment. HER-2 is an important indicator for targeted therapy in breast cancer and is also a mandatory test item for breast cancer. CD117 has both diagnostic value and provides reference for targeted therapy in gastrointestinal stromal tumors (GIST).

Assessing Tumor Prognosis

Tumor proliferative activity and infiltration and metastasis have important reference value for assessing patient prognosis. Immunohistochemical markers for tumor proliferative activity include proliferating cell nuclear antigen (PCNA), Ki67, and various growth factor receptors, which also have reference significance for distinguishing benign and malignant tumors. As mentioned earlier, there are also some markers that can be used for tumor infiltration and metastasis, such as basement membrane and myoepithelial markers for distinguishing carcinoma in situ and invasive carcinoma.

Classifying Diseases

The functional classification of endocrine tumors is often based on the hormones secreted by tumor cells. Pituitary adenomas can be classified into 10 types based on the hormones they secrete, such as growth hormone adenoma and prolactin adenoma; the functional classification of islet cell tumors includes insulinoma, glucagonoma, etc., totaling 6 types. There are many classifications of malignant lymphoma, which also rely on immunohistochemical results for differentiation.

Improving Diagnostic Level

From a macro perspective, implementing immunohistochemistry helps improve the overall diagnostic level of the department and promotes precise pathological diagnosis. Some cases may seem ambiguous, but with the addition of immunohistochemistry, they become clear immediately, eliminating the need for hesitation and debate. This can also increase the proportion of certain types of diagnoses, enhance clinicians’ trust in the pathology department, and improve the academic status of the pathology department.

Improving Research Level

Research on many cases requires immunohistochemical support, and some research projects or academic papers, even graduate degree theses, can be completed relying on immunohistochemistry. This is undoubtedly beneficial for promotion. Especially using newly developed antibodies for case diagnosis and research makes it easier to achieve results. Clinical research papers supplemented with pathology and immunohistochemistry in research methods are also easier to publish. Collaborating with clinicians or participating in clinical research can also enhance clinical-pathological connections.

Increasing Economic Benefits

Implementing immunohistochemistry, although increasing workload, can also increase departmental income and improve economic benefits. If routine pathological examination is considered a basic product, then immunohistochemistry is deep processing, which can improve quality, taste, and added value. Why not do it?

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