by Jason Wasserman MD PhD FRCPC
November 2, 2025
Adenocarcinoma is a type of cancer that starts in the gland-forming cells that line the inside of the stomach. These cells normally make mucus and digestive juices that protect and aid the stomach in breaking down food. In this disease, the cells grow in an uncontrolled way, forming a tumour that can invade deeper layers of the stomach wall and spread to other parts of the body.
Adenocarcinoma is the most common type of stomach cancer, making up about 90 to 95 per cent of all cases. The outlook for a person with this diagnosis depends on how abnormal the cancer cells look under the microscope (a feature called histologic grade), how far the cancer has spread (known as stage), and whether cancer cells are found in nearby lymph nodes.
Adenocarcinoma of the stomach develops over time due to a combination of environmental, infectious, and genetic factors. The most common risk factors include chronic infection with Helicobacter pylori, a type of bacteria that damages the stomach lining and causes long-term inflammation, and infection with Epstein–Barr virus (EBV), which can alter the growth of stomach cells.
Other important factors include smoking, diets high in salt-preserved or smoked foods and low in fruits and vegetables, and a family history of stomach cancer. In some people, inherited genetic changes can also increase the risk. For example, mutations in the CDH1 gene cause hereditary diffuse gastric cancer, while mutations in the APC gene cause familial adenomatous polyposis, both of which are associated with stomach cancer.
Many people with early stomach cancer do not have symptoms. As the tumour grows, symptoms may include difficulty swallowing (dysphagia), early fullness after eating, unexplained weight loss, and persistent stomach pain or discomfort. Some people experience nausea, vomiting, or black stools, which may indicate gastrointestinal bleeding. Ongoing blood loss can lead to anemia, a condition characterised by a low red blood cell count, which causes fatigue and weakness.
The diagnosis of adenocarcinoma is made after a biopsy of the stomach lining is examined by a pathologist, a doctor who specializes in studying tissue under the microscope to diagnose disease. The process leading to diagnosis often begins when a patient has symptoms or a history of stomach inflammation.
Before a biopsy, your doctor will review your medical history, symptoms, and risk factors, including infections, diet, and smoking history. You will be asked to refrain from eating or drinking for several hours before the procedure to ensure your stomach is empty. A numbing spray or mild sedative may be given to help you stay comfortable during the exam.
A gastroscopy, also called an upper endoscopy, is performed to visually examine the inside of the stomach. During this procedure, your doctor gently passes a thin, flexible tube with a light and a camera, called an endoscope, through your mouth and into your stomach. The camera allows your doctor to look for ulcers, lumps, or irregular patches of tissue on a screen.
If any suspicious areas are detected, the doctor will take small tissue samples, called biopsies, using special instruments passed through the endoscope. The tissue samples are then preserved and sent to a pathologist for examination. The procedure typically takes 10 to 20 minutes, and patients can usually go home shortly after.
A pathologist examines the biopsy under the microscope to confirm the diagnosis. Cancer is identified when the normal glandular cells of the stomach lining are replaced by malignant cells that grow in a disorganized pattern and invade deeper tissue. The report describes the type of adenocarcinoma, the histologic grade, and whether the cancer exhibits features such as lymphovascular invasion (cancer cells present within blood or lymphatic vessels) or perineural invasion (cancer cells growing along nerves).
Both of these features are important because they increase the risk of the cancer spreading to other areas.
Once the diagnosis is confirmed by biopsy, imaging studies are used to determine how far the cancer has spread. A CT scan of the chest, abdomen, and pelvis helps identify cancer in nearby lymph nodes or distant organs. An endoscopic ultrasound (EUS) may be used to measure the depth of tumour growth into the stomach wall. In some cases, a PET-CT scan is performed to detect active disease throughout the body.
Pathologists describe several patterns of adenocarcinoma of the stomach based on how the tumour cells look under the microscope. These patterns provide information about tumour behaviour and may influence treatment.
Tubular adenocarcinoma is the most common type of cancer. It forms irregular glands that grow into deeper layers of the stomach wall.
Intestinal-type adenocarcinoma resembles the cells that line the intestine and often develops after chronic stomach inflammation or intestinal metaplasia, a precancerous change in the stomach’s lining.
Papillary adenocarcinoma forms finger-like projections called papillae that contain a core of connective tissue lined by tumour cells. These tumours tend to grow slowly and are often more well differentiated.
Mucinous adenocarcinoma produces large amounts of mucus, which collects in pools between tumour cells. When more than half of the tumour is made up of mucus, it is classified as mucinous. This type can be more aggressive and may spread more easily.
Diffuse-type or poorly cohesive adenocarcinoma consists of scattered tumour cells that spread through the stomach wall without forming glands. These cancers can be challenging to detect early and are more likely to spread quickly.
Signet ring cell carcinoma is a specific form of poorly cohesive adenocarcinoma. The tumour cells contain a large droplet of mucus that pushes the nucleus to the edge, giving the cell a signet ring appearance. This subtype tends to exhibit more aggressive behavior than other types.
The histologic grade describes how much the cancer cells resemble normal stomach cells. Tumours that look more like normal cells are described as well differentiated and tend to grow more slowly. In contrast, tumours that look very abnormal are called poorly differentiated or undifferentiated and often grow more quickly and spread earlier.
Adenocarcinoma of the stomach is graded based on how much of the tumour forms glands:
Well differentiated (grade 1): More than 95 per cent of the tumour forms glands.
Moderately differentiated (grade 2): Between 50 and 95 per cent of the tumour forms glands.
Poorly differentiated (grade 3): Less than 50 per cent of the tumour forms glands.
Undifferentiated: No gland formation is seen.
Your pathology report will include the grade because it helps predict how the tumour is likely to behave and whether additional treatment is needed after surgery.
The depth of invasion describes how far the tumour has grown into the layers of the stomach wall. Understanding these layers helps explain how stomach cancer spreads.
Mucosa: The mucosa is the innermost lining of the stomach. It includes the epithelial cells (where cancer begins), a layer of connective tissue called the lamina propria, and a thin muscle layer called the muscularis mucosae.
Submucosa: Beneath this is the submucosa, a supportive layer of connective tissue that contains blood vessels and lymphatics.
Muscularis propria: The muscularis propria is a thick muscle layer that helps the stomach contract to mix and move food.
Subserosa: The subserosa is a thin layer of connective tissue that lies just beneath the outer surface.
Serosa: The serosa is the smooth outer covering of the stomach that separates it from nearby organs.
As the tumour grows deeper, it becomes more likely to spread to lymph nodes or other parts of the body. The pathologic tumour stage (pT) is determined by how far the tumour has invaded these layers:
pT1a: The tumour is limited to the mucosa.
pT1b: The tumour has grown into the submucosa.
pT2: The tumour has spread into the muscularis propria.
pT3: The tumour has reached the subserosal tissue.
pT4a: The tumour has gone through the serosa.
pT4b: The tumour has invaded nearby organs such as the spleen, pancreas, or colon.
Lymph nodes are small immune organs that filter fluid and trap cancer cells. During surgery, lymph nodes near the stomach are removed and examined under the microscope to see if cancer has spread. Your pathology report will list how many lymph nodes were examined and how many contained cancer.
The pathologic nodal stage (pN) is based on the number of involved lymph nodes:
pN0: No cancer cells are found in any lymph nodes.
pN1: Cancer is found in 1 to 2 lymph nodes.
pN2: Cancer is found in 3 to 6 lymph nodes.
pN3a: Cancer is found in 7 to 15 lymph nodes.
pN3b: Cancer is found in 16 or more lymph nodes.
If cancer cells extend beyond a lymph node into the surrounding tissue, the report may mention extranodal extension, which is associated with a higher chance of recurrence.
A margin is the edge of the tissue removed during surgery. The pathologist examines the margins to determine whether the tumour was removed entirely.
A negative margin means no cancer cells are seen at the edge of the tissue, suggesting that the tumour was completely excised.
A positive margin means cancer cells are present at the edge of the tissue, suggesting that some cancer may remain and that additional treatment may be necessary.
Margins are usually described as proximal (nearest the esophagus), distal (nearest the small intestine), or radial (the outermost surface). If the omentum, a layer of fatty tissue near the stomach, is removed, its edges may also be examined and described as omental margins.

Biomarkers are specific features of a tumour that can help predict how it will behave and how it may respond to particular treatments. Your pathology report may include results for one or more biomarkers.
Mismatch repair proteins—MLH1, PMS2, MSH2, and MSH6—are part of the cell’s natural system for correcting DNA errors. When one or more of these proteins is missing, the tumour is described as mismatch repair deficient (MMR-deficient) or microsatellite instability-high (MSI-high).
Pathologists test for MMR proteins using a technique called immunohistochemistry (IHC). If all four proteins are present, the tumour is considered MMR-proficient. If one or more is missing, the tumour is MMR-deficient.
This result is important because MMR-deficient tumours often respond well to immunotherapy, and the finding may suggest an inherited condition called Lynch syndrome, which increases the risk of certain cancers. Genetic counselling and testing may be recommended, especially for younger patients or those with a family history of cancer.
HER2 (human epidermal growth factor receptor 2) is a protein that helps regulate cell growth. In some stomach cancers, the HER2 gene becomes overactive, resulting in an excessive amount of HER2 protein on the surface of tumour cells. This is called HER2-positive cancer.
HER2 testing is performed using immunohistochemistry (IHC) to determine the amount of HER2 protein present. Results are scored as 0, 1+, 2+, or 3+. Scores of 0 and 1+ are negative, 2+ is borderline, and 3+ is positive. If the IHC result is 2+, an additional test called fluorescence in situ hybridization (FISH) may be performed to see if there are extra copies of the HER2 gene.
HER2-positive tumours tend to grow faster, but they can also respond to targeted therapy with drugs such as trastuzumab (Herceptin), which specifically blocks the HER2 protein.
Claudin 18.2 (CLDN18.2) is a protein found in the tight junctions between normal stomach cells. Some stomach cancers continue to express this protein at high levels, making them potential candidates for new targeted therapies that specifically target cells with Claudin 18.2.
Testing for Claudin 18.2 is done using immunohistochemistry (IHC). The report describes how many tumour cells express the protein and how strongly they stain. If your tumour expresses Claudin 18.2, your doctor may discuss whether a Claudin 18.2–targeted therapy is available as part of your treatment plan.
After diagnosis, your medical team will use your pathology report and imaging results to plan your treatment. The team usually includes a surgeon, medical oncologist, radiation oncologist, and pathologist.
Treatment for adenocarcinoma of the stomach depends on the stage, biomarker results, and your overall health. Most patients are treated with a combination of surgery, chemotherapy, and sometimes radiation therapy. Some patients may receive chemotherapy before surgery (called neoadjuvant therapy) to shrink the tumour, while others may receive it after surgery (called adjuvant therapy) to reduce the chance of recurrence.
If your tumour is HER2-positive, Claudin 18.2–positive, or MMR-deficient, your oncologist may include targeted therapy or immunotherapy as part of your treatment plan. These therapies work by focusing on specific molecular changes within the tumour.
After treatment, you will have regular follow-up visits that include physical exams, blood work, and imaging to look for signs of recurrence. If part of your stomach is removed, your healthcare team will closely monitor your nutrition, weight, and vitamin levels and may recommend adjustments to your diet.
What histologic type and grade does my pathology report show?
How deeply has the tumour invaded the stomach wall (what is my pT stage), and have any lymph nodes been affected (what is my pN stage)?
Were the surgical margins free of cancer?
Did my tumour show lymphovascular invasion or perineural invasion?
What were the results of biomarker testing for MMR, HER2, and Claudin 18.2, and how do these results affect my treatment?
Do my results suggest an inherited cancer syndrome, and should I see a genetic counsellor?
What are the recommended treatments, and in what order will they be given?
How will my response to treatment and long-term health be monitored?