April 12, 2024

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Commonly used immunohistochemical indexes of lung cancer

Commonly used immunohistochemical indexes of lung cancer

Commonly used immunohistochemical indexes of lung cancer. TTF-1, P63, Ki-67…Interpretation of commonly used immunohistochemical indicators of lung cancer. 

Lung cancer is the malignant tumor with the highest morbidity and mortality in the world, and its diagnosis is inseparable from the “gold standard” of pathology.

Commonly used immunohistochemical indexes of lung cancer


This article summarizes the relevant immunohistochemical indexes of lung cancer.


01 Adenocarcinoma


TTF-1 (thyroid transcription factor-1) is expressed in the nucleus of thyroid follicular epithelium and alveolar epithelial cells. It is positively correlated with the degree of tumor differentiation. The worse the differentiation, the more likely the expression is lost.

TTF-1 is expressed in more than 70% of non-mucinous adenocarcinoma subtypes, small cell lung cancer, a small portion of undifferentiated large cell lung cancer and atypical carcinoids, a few typical carcinoids express TTF-1, while lung squamous cell carcinoma, interpleural carcinoma Dermatoma does not express;
In metastatic adenocarcinoma of the lung, TTF-1 is almost all negative, which is different from thyroid tumor: TG negative;
In addition, TTF-1 was found to be expressed in a small number of ovaries (3%-39%), endometrium (2%-23%) and cervical adenocarcinoma (4%).


NapsinA (new aspartic protease A) is expressed in normal alveolar type II epithelial cells and proximal and distal renal tubules, more than 80% is expressed in lung adenocarcinoma, and its sensitivity and specificity are better than TTF-1 ;
About 3% of lung squamous cell carcinomas are positive and lung neuroendocrine tumors are negative;
Some renal cell carcinomas, uterine and ovarian adenocarcinomas express NapsinA.


Almost 100% of lung adenocarcinomas express CK7, but CK7 has low specificity, and 30%-60% of lung squamous cell carcinomas are positive;
CK7 is also expressed in adenocarcinomas of breast, stomach, ovary, uterus, etc., it needs to be combined with TTF-1 and NapsinA.

02 Squamous cell carcinoma


More than 90% of lung squamous cell carcinomas are strongly nuclear positive, but 10%-33% of lung adenocarcinomas have focal low-level expression of P63.
P63 is also expressed in 15% of neuroendocrine carcinomas and 22% of small cell lung cancers.


P40 is one of the subtypes of P63 protein, and it is positively located in the nucleus. It is considered to be the most specific and sensitive squamous cell carcinoma marker.
Compared with P63, the sensitivity of P40 in lung squamous cell carcinoma is equivalent to that of P63, but it is almost not expressed in lung adenocarcinoma and lymphoma, so it is highly specific.


CK5/6 is mainly expressed in squamous epithelial cells, ductal epithelial basal cells, myoepithelial cells and mesothelial cells under normal conditions.
More than 3/4 of lung squamous cell carcinomas are positive, epithelioid mesothelial tumors are highly expressed, and 2%-33% of lung adenocarcinomas are focally positive.


DSG3 (desmosome glycoprotein) is expressed in 85%-90% of lung squamous cell carcinomas, and almost not expressed in lung adenocarcinomas (<2%).


03 Neuroendocrine tumors

CgA, Syn and CD56 are the most commonly used combinations of neuroendocrine markers. Among them, CgA has the strongest specificity, and CD56 is the most sensitive but lacks specificity.


Syn (synaptophysin) mainly exists in neuronal presynaptic vesicle membrane, adrenal medulla, carotid body, and neurological and epithelial neuroendocrine cells of skin and internal organs.
This antibody is mainly used to label neuroendocrine cells and their tumors.


CgA (chromaffin A) is a soluble acidic protein with the highest content in the human adrenal medulla. It is widely present in neurons, neuroendocrine cells and tumor cells.
It is mainly used to mark neuroendocrine tumors, such as pituitary tumors, islet cell tumors, pheochromocytomas, medullary thyroid carcinoma, carcinoids, etc.


Nerve cell adhesion molecules (NCAM, CD56) are expressed on NK cells and a small part of activated T lymphocytes and cells of neuroectodermal origin.
This antibody is a marker of NK cell lymphoma, and also a specific marker of choice for pulmonary neuroendocrine tumors.


Ki-67 (proliferation index) is an antigen related to cell proliferation. Its function is closely related to mitosis. It marks cells in the proliferation cycle. The higher the positive rate, the faster the tumor growth and the worse the tissue differentiation. Chemotherapy is also more sensitive.
Ki-67 has a dual role in diagnosis and grading of lung neuroendocrine tumors. For example, typical carcinoids have Ki-67 ≤ 5%, which is low grade, atypical carcinoids are 5%-20%, which is medium grade, and large cell lung cancer is usually ≥ 60%, which is high grade.

04 Differentiation of lung adenocarcinoma and lung squamous cell carcinoma

In most cases, the TTF-1/P63 combination can basically meet the discrimination between lung squamous cell carcinoma and lung adenocarcinoma, because usually they are positive for one adenocarcinoma and squamous cell carcinoma and the other is negative.
But what if there are special circumstances?
If both TTF-1/P63 are positive, it is inclined to diagnose adenocarcinoma, because P63 can be expressed in adenocarcinoma, and TTF-1 is almost not diffusely expressed in squamous cell carcinoma;
If both TTF-1/P63 are negative, adenocarcinoma is still suspected, because the lack of expression of TTF-1 in differential adenocarcinoma is more common, and the expression of P63 in squamous cell carcinoma is relatively stable.

05 How to distinguish between primary lung tumor and secondary tumor?

Primary lung adenocarcinoma and metastatic adenocarcinoma

Generally speaking, breast cancer, pancreatic cancer, prostate cancer, cervical adenocarcinoma, endometrial cancer, colon adenocarcinoma, and mesothelioma are more common among adenocarcinomas that metastasize to the lung. Metastases and primary tumors usually share common features. Antigen expression.

The difference between lung adenocarcinoma and metastatic adenocarcinoma (source: author)

Primary squamous cell carcinoma and metastatic squamous cell carcinoma of the lung

Squamous cell carcinoma may come from the esophagus, head and neck, skin and other parts. Currently, there is no effective marker to distinguish primary lung squamous cell carcinoma from metastatic squamous cell carcinoma.

06 Differentiation of lung cancer and pleural mesothelioma

For pleural mesothelioma, there is still a lack of 100% specific markers, so at least 2 mesothelial and 2 epithelial markers should be selected.

According to the sensitivity and specificity of the antibody, the best markers of mesothelioma are Calretinin, CK5/6, Wilms tumor gene-1 (WT-1), MC and D2-40 .

07 Differentiation of large cell lung cancer

The WHO defines large cell lung cancer in this way—an undifferentiated non-small cell lung cancer that lacks the characteristics of small cell carcinoma, adenocarcinoma, and squamous cell carcinoma in terms of cytology, histological structure, and immunophenotype, and must be surgical Excise the specimen.

According to the definition of large cell lung cancer, it is not difficult to see that it is an exclusive diagnosis after excluding small cell carcinoma, adenocarcinoma and squamous cell carcinoma.


(source:internet, reference only)

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