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Questions and Answers
What type of gastric carcinoma comprises more than 90% of all gastric cancers?
Which area of the stomach is most frequently affected by distal gastric adenocarcinomas?
What genetic mutation is strongly associated with familial gastric cancer?
What symptom is common in advanced stages of gastric adenocarcinoma?
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Which factor is NOT associated with an increased risk of gastric cancer?
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What environmental factors contribute to the prevalence of gastric cancer?
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Which pathway is associated with intestinal-type gastric cancers?
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Which form of gastric cancer is associated with a loss of E-cadherin expression?
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Which type of gastric carcinoma has the best prognosis?
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What is a common characteristic of infiltrative tumors of gastric adenocarcinoma?
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What is the typical male-to-female ratio for the mean age of presentation in intestinal-type gastric cancer?
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Which lymph node is commonly involved in gastric cancer metastases?
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What factor is a significant prognostic indicator in gastric cancer?
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What treatment typically remains the preferred approach for resectable early gastric cancer?
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Which statement about the incidence of diffuse gastric cancer is true?
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What is the 5-year survival rate for advanced gastric cancer?
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What type of gastric cancer is more commonly associated with intestinal type carcinoma?
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Which host factor is linked to gastric cardia adenocarcinoma?
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Which genetic alteration is associated with the intestinal type of gastric cancer?
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What is a characteristic gross feature of diffuse type gastric cancer?
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Which of the following is NOT a feature of intestinal type gastric cancer?
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What histological feature characterizes diffuse type gastric cancer?
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Which condition is associated with an increased risk of developing cancer in the residual gastric stump?
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What could result from the release of extracellular mucin in gastric cancer?
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Study Notes
Gastric Adenocarcinoma
- Most common malignancy of the stomach, representing over 90% of gastric cancers.
- Predominantly occurs in the gastric antrum, with the lesser curvature being more frequently affected.
- Initial signs often mimic chronic gastritis and peptic ulcer disease, including indigestion, difficulty swallowing, and nausea.
- Advanced stages manifest with weight loss, loss of appetite, early satiety (especially in diffuse cancers), anemia, and bleeding.
Genetics and Pathogenesis
- Familial gastric cancer strongly correlates with germline loss-of-function mutations in the CDH1 gene, encoding E-cadherin (a cell adhesion protein).
- Diffuse gastric carcinomas frequently exhibit loss-of-function mutations in CDH1 (around 50% of cases), with decreased E-cadherin expression in the rest.
- E-cadherin loss plays a crucial role in the development of diffuse gastric cancer.
- Intestinal-type gastric cancers are strongly linked to mutations enhancing Wnt pathway signaling, including:
- Loss-of-function mutations in the APC gene (adenomatous polyposis coli).
- Gain-of-function mutations in the β-catenin gene.
- Other mutations affecting TGF-β signaling, apoptosis (BAX), and cell cycle control (CDKN2A) are also associated with intestinal-type gastric cancers.
- Individuals with familial adenomatous polyposis (FAP) due to germline APC mutations have an increased risk of intestinal-type gastric cancer.
- Proinflammatory gene variants, such as IL-1β and IL-1 receptor, are associated with an elevated risk of gastric cancer in individuals with Helicobacter pylori gastritis.
Environmental Factors
- Gastric cancer is more prevalent in lower socioeconomic groups and individuals with multifocal mucosal atrophy and intestinal metaplasia.
- Helicobacter pylori infection is more commonly associated with intestinal type carcinoma.
- Peptic ulcer disease is linked to a reduced risk of gastric cancer, but individuals after partial gastrectomies for peptic ulcer disease have a slightly higher cancer risk in the residual gastric stump.
- N-nitroso compounds and benzo[a]pyrene, used as food preservatives, are associated with an increased risk of gastric cancer.
- Smoked and salted foods are linked to a heightened risk.
Host Factors
- Chronic gastritis is a significant risk factor.
- Barrett's esophagus (chronic gastroesophageal reflux disease and obesity) with intestinal metaplasia increases the risk of gastric cardia adenocarcinoma.
- Menetrier's disease is associated with gastric cancer risk.
- Gastric adenomas are considered precursors to gastric cancer.
Intestinal vs. Diffuse Type
Intestinal Type
- Genetics: Loss-of-function mutations in APC, gain-of-function mutations in β-catenin, and mutations affecting TGF-β signaling, apoptosis (BAX), and cell cycle control (CDKN2A).
- Gross Appearance: Bulky, exophytic mass with ulcerative infiltrative lesion and heaped-up borders.
- Microscopy (M.E.): Gland formation within an infiltrative desmoplastic stroma.
Diffuse Type
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Genetics: Loss-of-function mutations, hypermethylation, or silencing of the CDH1 (E-cadherin) gene.
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Gross Appearance: Diffuse infiltrative growth pattern with markedly thickened gastric walls and partial loss of rugosity (linitis plastica/leather bottle appearance), with no distinct mass.
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Microscopy (M.E.): Diffuse permeation of gastric wall by small clusters and individual discohesive cells due to the absence of E-cadherin. Cells lack gland formation and exhibit large mucin vacuoles, pushing the nucleus to the periphery, giving a signet-ring cell morphology.
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Mucin release in both types can lead to large mucin lakes formation
Depth of Invasion and Prognosis
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Early Gastric Carcinoma (Superficial Spreading Type): Limited to mucosa and submucosa, regardless of lymph node involvement. Holds the best prognosis.
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Advanced Gastric Carcinoma: Extends beyond submucosa into the muscular wall.
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Depth of invasion, nodal spread (lymph node involvement), and distant metastases are the major prognostic indicators for gastric cancer.
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Invasion of the duodenum, pancreas and retroperitoneum is common in advanced cases.
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Surgery is the preferred treatment approach when possible, offering a 5-year survival rate exceeding 90% for early gastric cancer, even with lymph node metastasis.
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The 5-year survival rate for advanced gastric cancer remains below 20%.
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Overall 5-year survival for gastric cancer is less than 30% due to late diagnosis.
Clinical Features
- Intestinal-type gastric cancer is more common in high-risk regions and arises from precursor lesions like flat dysplasia and adenomas.
- Median age of presentation: 55 years, with a male-to-female ratio of 2:1.
- Incidence of diffuse gastric cancer is relatively consistent across different regions, without identifiable precursor lesions, and prevalence is similar in males and females.
- The remarkable decrease in gastric cancer incidence primarily affects the intestinal type, resulting in similar incidences of both types in many areas.
- Metastases frequently occur at diagnosis, with common sites including:
- Supraclavicular sentinel lymph nodes (Virchow node).
- Periumbilical lymph nodes (Sister Mary Joseph nodule).
- Ovaries (Krukenberg tumor).
- Left axillary lymph node.
- Pouch of Douglas.
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Description
This quiz explores the key aspects of gastric adenocarcinoma, the most common gastric cancer. It covers its pathology, genetic factors, and clinical manifestations, including the relationship with CDH1 mutations. Test your knowledge on this prevalent malignancy and its genetic underpinnings.
