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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Gastroenterology

Monitoring Your Health: Surveillance and the Cambridge Protocol

At a Glance

Patients with Hereditary Diffuse Gastric Cancer (HDGC) mutations require specialized surveillance using the Cambridge Protocol, which involves taking over 30 random stomach biopsies. Endoscopies can miss hidden cells, so mutation carriers also need targeted breast and colon screenings.

Because Hereditary Diffuse Gastric Cancer (HDGC) does not grow in a single, obvious lump, doctors must use a very specific and intensive method to look for it. This process is called surveillance, and its goal is to find microscopic cancer cells before they can spread [1][2].

The Cambridge Protocol

Standard endoscopies (where a camera is used to look at the stomach) are often not enough for people with CDH1 or CTNNA1 mutations. Instead, experts use the Cambridge Protocol. This is a highly systematic “mapping” of the stomach [1].

  • 30+ Random Biopsies: During the procedure, the doctor will take at least 30 small tissue samples (biopsies) from specific zones throughout the entire stomach—even if the tissue looks perfectly healthy [1].
  • Targeted Hunting: The doctor also looks for “pale areas” or subtle mucosal patches, which can sometimes be a sign of hidden cancer cells [3][4].
  • Expert Centers: This protocol is best performed at specialized centers where endoscopists are trained specifically to spot the subtle signs of HDGC [2].

The Challenge of “Under the Surface” Growth

It is important to understand that endoscopy has a high false-negative rate for HDGC [5]. This means a test can come back “clear” even if microscopic cancer is present.

  • Submucosal Growth: Signet ring cells often start growing in the lamina propria—a layer of the stomach wall that is just beneath the surface [6][7].
  • Hidden Foci: These tiny clusters of cells (foci) are often smaller than a pinhead and may be covered by a layer of normal-looking stomach lining, making them invisible to the camera [5][8].
  • The “Gold Standard”: Because surveillance can miss these hidden cells, prophylactic total gastrectomy (preventative stomach removal) remains the most reliable way to eliminate the risk [1][5].

Beyond the Stomach: Breast and Colon Health

The mutations that cause HDGC can affect other parts of the body as well.

1. Breast Cancer (Lobular)

Women with a CDH1 mutation have a significantly higher risk of lobular breast cancer [9].

  • Annual MRI and Mammograms: Current guidelines recommend starting annual breast MRI surveillance at age 30, often alternating with a mammogram or ultrasound every 6 months to provide comprehensive coverage [10][11].
  • Why MRI? Lobular breast cancer, like diffuse stomach cancer, spreads in a “spider-web” pattern that is often hard to see on a standard mammogram alone [12].

2. Colon Cancer

While the link is not as strong as the stomach or breast cancer risks, some studies suggest a potential increase in colon cancer risk for CDH1 carriers [13]. Doctors often recommend starting regular colonoscopies earlier than the general population, though specific timelines should be discussed with your genetic counselor [14].

3. Cleft Lip and Palate

Families with CDH1 mutations sometimes have a history of cleft lip or cleft palate [15][16]. If you or a family member had this at birth, it can be a “clue” that helped lead to your HDGC diagnosis [17].

Summary of Recommended Surveillance

Area Screening Method When to Start
Stomach Cambridge Protocol Endoscopy Varies; often late teens/early 20s [1]
Breast (Women) Breast MRI (+ Mammogram) Age 30 [11]
Colon Colonoscopy Discuss with specialist (often age 40 or earlier) [14]

Surveillance is a partnership between you and your medical team. While it requires commitment, it is a vital tool for staying ahead of the disease [18].

Next Steps: Learn about surgical options in The Decision: Surgery and Your “New Normal”.
Back to the start: Home Page

Common questions in this guide

What is the Cambridge Protocol for HDGC surveillance?
The Cambridge Protocol is a specialized endoscopy procedure used for patients with HDGC mutations. During the test, a doctor takes at least 30 random tissue biopsies from throughout the stomach, even if the tissue looks completely healthy, to check for microscopic cancer cells.
Can a standard endoscopy miss diffuse gastric cancer?
Yes, standard endoscopies have a high false-negative rate for HDGC. The cancer cells often grow beneath the surface layer of the stomach lining, making them invisible to the standard camera view even when cancer is present.
What breast cancer screening is recommended for CDH1 mutation carriers?
Women with a CDH1 mutation have a higher risk of lobular breast cancer and are typically advised to start annual breast MRI screenings at age 30. Doctors often recommend alternating this with a mammogram or ultrasound every six months.
Why is preventative stomach removal considered the gold standard for HDGC?
Preventative removal of the stomach is considered the gold standard because surveillance endoscopies can easily miss microscopic cancer cells hiding under the stomach lining. Surgery is the most reliable way to completely eliminate the risk of stomach cancer.
Is there a link between HDGC and cleft lip or palate?
Yes, families with CDH1 mutations sometimes have a history of cleft lip or cleft palate. This personal or family history can be an important clinical clue that helps doctors diagnose Hereditary Diffuse Gastric Cancer.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does this hospital follow the 2020 IGCLC guidelines for my surveillance?
  2. 2.Who are the endoscopists here who have the most experience with the 'Cambridge Protocol'?
  3. 3.If my random biopsies come back clear, does that mean I am definitely cancer-free, or could signet ring cells still be hiding beneath the surface?
  4. 4.At what age should I start annual breast MRIs, and do you also recommend mammograms or ultrasounds?
  5. 5.Does my specific mutation (CDH1 vs. CTNNA1) change how often I should have a colonoscopy?

Questions For You

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References

References (18)
  1. 1

    Endoscopic Ultrasound Has Limited Utility in Diagnosis of Gastric Cancer in Carriers of CDH1 Mutations.

    Kumar S, Katona BW, Long JM, et al.

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2020; (18(2)):505-508.e1 doi:10.1016/j.cgh.2019.04.064.

    PMID: 31077828
  2. 2

    Hereditary Diffuse Gastric Cancer-Update Based on the Current Consort Recommendations.

    Treese C, Siegmund B, Daum S

    Current oncology (Toronto, Ont.) 2022; (29(4)):2454-2460 doi:10.3390/curroncol29040199.

    PMID: 35448173
  3. 3

    CDH1 Gene Mutation Hereditary Diffuse Gastric Cancer Outcomes: Analysis of a Large Cohort, Systematic Review of Endoscopic Surveillance, and Secondary Cancer Risk Postulation.

    Benesch MGK, Bursey SR, O'Connell AC, et al.

    Cancers 2021; (13(11)) doi:10.3390/cancers13112622.

    PMID: 34073553
  4. 4

    Factors associated with detection of hereditary diffuse gastric cancer on endoscopy in individuals with germline CDH1 mutations.

    Laszkowska M, Tang L, Vos E, et al.

    Gastrointestinal endoscopy 2023; (98(3)):326-336.e3 doi:10.1016/j.gie.2023.04.2071.

    PMID: 37094689
  5. 5

    Random biopsies in patients harboring a CDH1 mutation: time to change the approach?

    Castro R, Lobo J, Pita I, et al.

    Revista espanola de enfermedades digestivas 2020; (112(5)):367-372 doi:10.17235/reed.2020.6720/2019.

    PMID: 32338015
  6. 6

    Overview on new progress of hereditary diffuse gastric cancer with CDH1 variants.

    Hu MN, Hu SH, Zhang XW, et al.

    Tumori 2020; (106(5)):346-355 doi:10.1177/0300891620949668.

    PMID: 32811340
  7. 7

    A Comprehensive Literature Review of the CDH1 Mutation and Its Role in Gastric Cancer.

    Samardali M, Samardaly J, Shanti I

    Cureus 2025; (17(5)):e85072 doi:10.7759/cureus.85072.

    PMID: 40585607
  8. 8

    Enhanced endoscopic detection of occult gastric cancer in carriers of pathogenic CDH1 variants.

    Curtin BF, Gamble LA, Schueler SA, et al.

    Journal of gastroenterology 2021; (56(2)):139-146 doi:10.1007/s00535-020-01749-w.

    PMID: 33206267
  9. 9

    First report of a Mexican family with mutation in the CDH1 gene.

    Martínez Valenzuela C, Castelán-Maldonado EE, Carvajal-Zarrabal O, Calderón-Garcidueñas AL

    Molecular genetics & genomic medicine 2020; (8(11)):e1208 doi:10.1002/mgg3.1208.

    PMID: 32886433
  10. 10

    Hereditary lobular breast cancer with an emphasis on E-cadherin genetic defect.

    Corso G, Figueiredo J, La Vecchia C, et al.

    Journal of medical genetics 2018; (55(7)):431-441 doi:10.1136/jmedgenet-2018-105337.

    PMID: 29929997
  11. 11

    Hereditary Diffuse Gastric Cancer Syndrome and the Role of CDH1: A Review.

    Gamble LA, Heller T, Davis JL

    JAMA surgery 2021; (156(4)):387-392 doi:10.1001/jamasurg.2020.6155.

    PMID: 33404644
  12. 12

    Multidisciplinary management of CDH1 germinal mutation and prophylactic management hereditary lobular breast cancer: A case report.

    Mirandola S, Pellini F, Granuzzo E, et al.

    International journal of surgery case reports 2019; (58()):92-95 doi:10.1016/j.ijscr.2019.03.053.

    PMID: 31028995
  13. 13

    Colonic Metastasis in a Patient With Hereditary Diffuse Gastric Cancer: A Case Report.

    John S, Cantu Lopez C, Herrera-Gonzalez S, Bains Y

    Cureus 2024; (16(5)):e59483 doi:10.7759/cureus.59483.

    PMID: 38826894
  14. 14

    CDH1 Gene and Hereditary Diffuse Gastric Cancer Syndrome: Molecular and Histological Alterations and Implications for Diagnosis And Treatment.

    Luo W, Fedda F, Lynch P, Tan D

    Frontiers in pharmacology 2018; (9()):1421 doi:10.3389/fphar.2018.01421.

    PMID: 30568591
  15. 15

    Cleft lip/palate and hereditary diffuse gastric cancer: report of a family harboring a CDH1 c.687 + 1G > A germline mutation and review of the literature.

    Obermair F, Rammer M, Burghofer J, et al.

    Familial cancer 2019; (18(2)):253-260 doi:10.1007/s10689-018-0111-5.

    PMID: 30306390
  16. 16

    E-cadherin variants associated with oral facial clefts trigger aberrant cell motility in a REG1A-dependent manner.

    Pereira J, Melo S, Ferreira RM, et al.

    Cell communication and signaling : CCS 2024; (22(1)):152 doi:10.1186/s12964-024-01532-x.

    PMID: 38414029
  17. 17

    Dental agenesis as a novel phenotypical feature associated with hereditary diffuse gastric cancer in China.

    Wang Z, Ding Q, Xu J, et al.

    Journal of medical genetics 2025; doi:10.1136/jmg-2025-111081.

    PMID: 41130721
  18. 18

    Surveillance and Surgical Considerations in Hereditary Diffuse Gastric Cancer.

    Gamble LA, Davis JL

    Gastrointestinal endoscopy clinics of North America 2022; (32(1)):163-175 doi:10.1016/j.giec.2021.08.009.

    PMID: 34798984

This page explains surveillance guidelines for Hereditary Diffuse Gastric Cancer for educational purposes. Always consult your genetic counselor and specialized oncology team to develop a personalized screening plan.

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