Claudin 18.2


Claudin 18.2 is a protein that helps cells stick tightly together, creating barriers between different compartments in the body. It is one form of a protein called claudin 18, specifically found in the cells lining the stomach. Claudin 18.2 is important because it is abnormally expressed (present when it normally shouldn’t be) in certain cancers, making it a target for specific treatments.

What types of normal cells and tissues express claudin 18.2?

In healthy tissues, claudin 18.2 is primarily found in the lining of the stomach (gastric epithelial cells). It can also be found in Paneth cells in the duodenum (the first part of the small intestine). Its expression outside of these tissues is usually minimal or absent.

How do pathologists test for claudin 18.2?

Pathologists test for claudin 18.2 using a laboratory technique called immunohistochemistry (IHC). This test uses antibodies that specifically bind to the claudin 18.2 protein, causing a visible color change when examined under a microscope.

Interpreting your claudin 18.2 results

When your pathologist examines your tissue for claudin 18.2, they look at the pattern and intensity of staining around the outer edges (membranes) of cancer cells. This membranous staining can appear as complete circles around cells, partial outlines, or staining along one side of the cell.

Your report will typically include two important pieces of information:

  • Staining intensity: This is scored on a scale from 0 to 3+, where:

    • 0 means no staining.

    • 1+ (weak) means faint staining.

    • 2+ (moderate) means clear and noticeable staining.

    • 3+ (strong) means very intense staining.

  • Percentage of positive cells: This tells you how many cancer cells (out of at least 50 counted) showed moderate to strong staining.

For gastric or gastroesophageal junction cancers, the tumour is considered positive for claudin 18.2 if 75% or more of the cancer cells have moderate (2+) to strong (3+) membranous staining. A positive result indicates your cancer may respond to therapies specifically targeting claudin 18.2.

These tests can be performed on tissue obtained from a biopsy or surgery, either from the original cancer site or from a metastatic site. Discussing your specific results with your doctor will help you understand how this information impacts your treatment options.

What types of benign (non-cancerous) conditions express claudin 18.2?

Claudin 18.2 can be expressed in various non-cancerous conditions affecting the stomach and esophagus, including:

What types of malignant (cancerous) tumours express claudin 18.2?

Claudin 18.2 is expressed in various malignant tumours, most notably:

  • Gastric (stomach) adenocarcinoma: Approximately 70% of intestinal-type and 60% of diffuse-type cancers show some expression; about 35–40% show enough expression to be eligible for targeted treatments.

  • Gastroesophageal junction adenocarcinoma: Frequently expresses claudin 18.2 (around 75–78% with any staining; 35–40% with high expression eligible for treatment).

  • Pancreatic adenocarcinoma: Approximately 68–80% of cases show expression of claudin 18.2.

  • Gastric neuroendocrine tumours: About 80% express this protein.

Tumours originating outside these areas, such as esophageal squamous carcinoma, ovarian cancers, colorectal metastases, or pancreatic neuroendocrine carcinomas, typically do not express claudin 18.2.

Why do pathologists test for claudin 18.2?

Pathologists test for claudin 18.2 expression because:

  • It helps identify cancers, particularly gastric or gastroesophageal junction adenocarcinomas, that may respond to specific targeted treatments (such as zolbetuximab, an antibody drug targeting claudin 18.2).

  • It helps determine if metastatic cancers originated in the stomach or pancreas versus other locations.

  • It can distinguish gastric neuroendocrine tumours from neuroendocrine tumours that originated in other body parts.

Currently, testing for claudin 18.2 is an FDA-approved companion diagnostic for selecting appropriate targeted therapies in gastric and gastroesophageal junction cancers.

Prognostic significance of claudin 18.2

Claudin 18.2 expression alone does not significantly affect how quickly a gastric cancer progresses or a patient’s overall survival without targeted therapy. However, gastric cancers positive for claudin 18.2 more frequently spread to the peritoneum (lining of the abdominal cavity).

Importantly, patients with claudin 18.2-positive gastric or gastroesophageal junction adenocarcinomas may benefit significantly from treatments targeting claudin 18.2 (such as zolbetuximab) combined with chemotherapy, leading to improved overall survival.

Questions for your doctor

  • Has my tumour been tested for claudin 18.2 expression?

  • If so, is my tumour positive for claudin 18.2, and what does that mean for my treatment options?

  • Would I benefit from targeted treatments such as zolbetuximab?

  • Are there clinical trials or new treatments targeting claudin 18.2 available for my condition?

  • Does my claudin 18.2 status affect my prognosis or likelihood of the cancer spreading?

  • Will additional tests or biopsies be required to confirm my claudin 18.2 status?

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