Date：2021-04-19

The Pathology of Gastric Cancer – Different Types of Gastric Cancer

Adenocarcinoma, accountable for approximately 95% of all gastric cancers, is the most common type of gastric cancer. Remaining forms of gastric cancer consist of malignant lymphoma and leiomyosarcoma. Gastric adenocarcinoma can additionally be categorised into two types: intestinal and diffuse. Intestinal gastric cancer generally has fairer prognoses as the specified gene mutations in its cancer cells allow patients with this type of gastric cancer to receive targeted therapy. On the other hand, diffuse gastric cancer cells spread comparatively quicker and are consequently more difficult to treat, leading to poorer prognoses. Furthermore, diffuse gastric cancer tends to metastasize to the entire stomach instead of staying constrained to one area. An estimated 20% of gastric cancers are diffuse gastric cancer, and amongst these, a small percentage of cases are caused by hereditary diffuse gastric cancer (HDGC).

Hereditary Diffuse Gastric Cancer

Hereditary diffuse gastric cancer is a rare genetic disease. Though gastric cancer usually occurs in people over 60 years old, individuals with HDGC will develop it at an earlier age, with an average of 38 years old at diagnosis. The gene often associated with hereditary diffuse gastric cancer is CDH1, but CDH1 gene mutations are only found in about 20-30% of families with HDGC. Therefore, when considering whether members of the family have a risk of developing HDGC, both clinical and genetic aspects should be taken into account.

The CDH1 gene mutation is correlated to stomach cancer and other related diseases (such as breast cancer in women). People with this gene mutation have a 50% chance of passing the mutation down to the next generation. However, not everyone with a mutation in the CDH1 gene will develop cancer. In people with CDH1 gene mutations, the lifetime risk of developing diffuse gastric cancer is about 67%-70% for men and 56%-83% for women, whereas the lifetime risk of developing breast cancer is 39%-52%.

If My Family Member Has Stomach Cancer, Is There A Chance It Is Hereditary?

According to the recommendations of the National Comprehensive Cancer Network (NCCN), if an individual or family member is found to possess any of the following conditions, they may be suspected of having a genetic mutation related to hereditary diffuse gastric cancer, and genetic testing for hereditary gastric cancer should be considered:

• There are two cases of gastric cancer in the family, one of which is diagnosed as diffuse gastric cancer, regardless of the age of the individual;
• The individual was diagnosed with diffuse gastric cancer before the age of 50, yet has no family history of such;
• The individual was diagnosed with diffuse gastric cancer or breast cancer for themselves or a family member before the age of 70;
• Two family members were diagnosed with breast cancer before the age of 50;
• The individual is of Maori descent and was diagnosed with diffuse gastric cancer at any age, or has a personal or family history of cleft lip or palate;
• The individual was diagnosed with bilateral breast cancer before the age of 70.

Prevent Diffuse Gastric Cancer

Diffuse gastric cancer is difficult to detect, has a low survival rate, a poor prognosis, and a high recurrence rate. It is a daunting rare cancer. Studies have shown that gastroscopy usually misses early-stage diffuse gastric cancer, so it is difficult to diagnose hereditary diffuse gastric cancer early. People with CDH1 gene mutations can discuss with their doctors and consider preventive surgery. Carriers who decide not to undergo preventive surgery should consider regular gastric mucosal biopsies per year.

Reference:

American Society of Clinical Oncology (ASCO). Hereditary Diffuse Gastric Cancer. 01/2020. https://www.cancer.net/cancer-types/hereditary-diffuse-gastric-cancer

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Gastric Cancer. Version 1.2021, February 9, 2021.