September 26, 2023

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Common immunohistochemical indexes for gastric cancer

Common immunohistochemical indexes for gastric cancer

Common immunohistochemical indexes for gastric cancer.   Immunotherapy-related immune markers: CK, HER2, Ki-67…

Common immunohistochemical indexes for gastric cancer

According to the 2020 Global Cancer Report, the incidence of gastric cancer ranks 5th in the world, and the mortality rate ranks 4th in the world. Understanding and familiarizing with the interpretation of the results of gastric cancer immunohistochemistry is particularly important for the diagnosis and treatment of gastric cancer and prognostic analysis.


The immunohistochemical indicators of gastric cancer are complicated, and many doctors are stumped after getting the immunohistochemical report. This article explains the immunohistochemical indicators of gastric cancer, hoping to help clinical work!


1 Common pathological types of gastric cancer

Common adenocarcinoma

Different degrees of expression of CK, CK-L, CK7, CK20, Villin (partial), CK19, CDX2, CEA (partial), HER2;

Does not express squamous cell carcinoma markers (such as CK-H, P63, TTF-1, etc.).

Intestinal epithelium (expressing MUC2, CDX2, CD10, etc.) or pit epithelium (expressing MUC1, MUC5AC, MUC6, etc.) phenotypes often appear.

Special staining AB/PAS staining shows AB-positive blue-stained intestinal mucus (acid glycoprotein) or purple gastric mucus (neutral glycoprotein) in the plasma.

Note: Low-molecular-weight CK (CK-L): including CK7, CK20, CK8, CK18, CK19, etc. It mainly exists in monolayer epithelium and glandular epithelial cells, and is mainly used for the diagnosis and differential diagnosis of visceral glandular epithelial tumors.


Adenosquamous carcinoma

Each component requires a ratio of >25%. This type of cancer is often associated with deep invasion, lymph node metastasis and poor prognosis.

Suggested immune markers: CK5/6 (or add 34βE12, P63, P40), CK8/18 and CK7, etc.


Carcinoma with lymphocytic stroma

Also called lymphoepithelioid carcinoma or medullary carcinoma.

More than 80% of patients are related to EBV infection, which is more common in male patients, proximal stomach or remnant stomach. The rest is related to microsatellite instability (MSI) (remote gastric cancer, more common in elderly patients).

Tumor cells showed pushing margins, mostly distributed in irregular sheets, syncytial and polygonal cells with a large number of lymphocyte infiltration, sometimes lymphoid follicles, and occasionally granulomas and osteoclast-like giant cells.

The lymphocytes are mainly CD8+ T cells, and more B lymphocytes and plasma cells may appear in the advanced stage.

The prognosis of this subtype of gastric cancer is better than that of ordinary adenocarcinoma, with a low recurrence rate, low lymph node metastasis rate, and a 5-year survival rate of about 77%.


Hepatoid adenocarcinoma

HepPar-1, AFP, CK19 and CDX2 are often positively expressed in varying degrees.

The tumor is composed of two components (liver-like differentiated area + ordinary adenocarcinoma area), with transitions visible between them. The liver-like differentiated area cancer cells are polygonal, with rich eosinophils, large and irregular nuclei, in the middle, and obvious nucleoli. , Interstitium is rich in sinusoids, similar to HCC.

Bile or PAS/PAS-D staining positive eosinophilic glass-like globules can be seen in the cytoplasm of cancer cells in the liver-like differentiation zone.

It is mainly differentiated from hepatocellular carcinoma, which often does not express CK19 and CDX2.


Squamous cell carcinoma

Different degrees of expression of CK-H, P63, TTF-1 and so on.

Note: High molecular weight CK (CK-H): This antibody reacts with 1, 5, 10, 14 cytokeratin and is expressed on squamous epithelium, ductal epithelium and other stratified epithelium.


Undifferentiated carcinoma

Diffuse expression of CK, CAM5.2, EMA, a small number of Vimentin positive. When it is necessary to identify undifferentiated malignant tumors of the stomach, it is recommended to use a set of antibodies such as CKpan, CAM5.2, EMA, LCA, etc. Individual lymphomas are positive for CK.


1) Broad-spectrum cytokeratin (CKpan): Mark all monolayer epithelium, stratified epithelium, transitional epithelial cells, benign and malignant tumors derived from various epithelial cells, synovial tumors and mesothelioma, etc., a small part of mesenchymal origin Tumors can also be positive.

2) CAM5.2: also known as very low molecular weight cytokeratin, which is mainly expressed in secretory epithelial cells and tumors derived from them. Stratified squamous epithelium and urothelium are not expressed, but in some poorly differentiated squamous cell carcinomas It can also be positively expressed in.

3) Vimentin: expressed in normal mesenchymal cells and tumors derived from them. It is mainly used to mark malignant tumors of mesenchymal origin, such as myogenic tumors, soft tissue tumors and bone tumors. It is of great significance in the differentiation of cancer and sarcoma, malignant melanoma and poorly differentiated cancer, undifferentiated cancer and lymphoma.

4) LCA (CD45): LCA is a common antigen of white blood cells and a specific marker of hematopoietic cells. It is mainly distributed on the surface of T cells, B cells, monocytes, granulocytes and precursor cells. Generally not present in non-hematopoietic tissues, it is a commonly used marker to distinguish lymphoma, leukemia and non-hematopoietic tissue tumors.



How to distinguish it from neuroendocrine cancer?

The morphology of gastric neuroendocrine carcinoma is very similar to that of lung large or small cell neuroendocrine carcinoma, and immunohistochemical indicators such as CKpan, Syn, CgA, and CD56 can be selected for identification.

10%-61% of gastric adenocarcinomas can express CgA and Syn, but they are generally negative for CD56. If there is no differentiation of neuroendocrine cells, it cannot be considered a neuroendocrine tumor.


How to judge whether it is primary or secondary?

Secondary tumors are not common. The lesions are mostly large ulcers or submucosal masses. Under gastroscopy, they are mostly solitary lesions, often involving the proximal stomach and gastric body.

Note: Cadherin 17 (Cadherin17, CDH17) is a marker of adenocarcinoma of the digestive system. In normal tissues, the epithelial cells of the gastrointestinal tract and pancreatic duct can be labeled, but the kidney, liver or other tissues are not labeled.

In tumor tissues, it can be used to label digestive system adenocarcinoma (including liver cancer). It is positively expressed in 81% of metanephric adenomas, and CDH17 is rarely positive in non-digestive tract tumors.



2 Chemotherapy-related immune markers


It is often used to evaluate the proliferation activity of cancer cells. Generally speaking, chemotherapy drugs are only effective for tumor cells that enter the cell division cycle (G1, S, G2, and M phases). The higher the Ki-67 positive rate means that the drug can enter more cell division cycles, then the chemotherapy drug The sensitivity will also be higher.


3 Targeted therapy-related immune markers


The HER2 protein is a transmembrane tyrosine kinase receptor and belongs to the EGFR family. HER2 is a predictor of targeted therapy, that is, patients with positive gastric cancer can be treated with trastuzumab.

Both gastroscopic biopsy specimens and surgical specimens are suitable for HER2 detection;

For patients who cannot obtain biopsy tissue, liquid biopsy HER2 amplification can be used (the copy number of HER2 gene somatic cell copy number results of ctDNA targeted sequencing in the blood are highly consistent with fluorescence in situ hybridization data).

NTRK gene fusion

Patients with NTRK fusion-positive tumors can be treated with TRK inhibitors (such as larotrectinib or entrectinib), and have a high response rate (>75%).

NTRK gene fusion involves NTRK1, NTRK2 or NTRK3, and is the oncogenic driving factor for many types of tumors. These fusions can be detected using a variety of methods, including tumor DNA and RNA sequencing, and plasma free DNA.



4 Immunotherapy-related immune markers

Immune checkpoint inhibitor therapy targeting programmed death receptor-1 (PD-1) and its ligand (PD-L1) has become a hot spot in tumor immunotherapy in recent years. The expression rate of PD-L1 in gastric cancer is 12%-50%, which is closely related to the infiltration of CD8 cells. It is also positively related to intestinal type, proximal gastric cancer, EBV positive, MSI-H, etc.

For patients with gastric cancer who are to be treated clinically with PD-1/PD-L1 inhibitors, it is recommended to evaluate the microsatellite instability (MSI)/mismatch repair defect (MMR) status, PD-L1 expression and the EBV infection status of tumor tissues.




(source:internet, reference only)

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