Stomach cancer pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D.[2], Parminder Dhingra, M.D. [3], Mohammed Abdelwahed M.D[4]

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Gastric cancer may occur secondary to a variety of causes including H. pylori and gastric cancer have strong correlation. This is related to nitric oxide accumulation produced by inflammatory cells responding to H. pylori infection. The pathophysiology of stomach cancer depends upon the histologic subtype. K-ras mutations is found in invasive cancers and intestinal metaplasia. Inactivation of p53 in gastric epithelial cells reduce their ability to undergo apoptosis. DNA methylation of gene promoters can silence the expression of CDH1. Beta-catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Diffuse gastric carcinomas do not have a precancerous lesion. They are highly metastatic with a poorer prognosis than intestinal cancers. When the entire stomach wall is infiltrated, it results in a rigid thickened stomach wall called linitis plastica. There are many diseases associated with gastric cancer such as, hereditary diffuse gastric cancer, gastric adenocarcinoma, proximal polyposis of the stomach, Lynch syndrome, familial adenomatous polyposis, Li-Fraumeni syndrome, Peutz Jeghers syndrome, juvenile polyposis, hereditary breast and ovarian cancer syndrome and Cowden's syndrome. There are five gross pathological types of gastric cancer; superficical, ulcerative, infiltrative ulcerative, diffuse infiltrative, and unclassified. There are two major histological classifications for gastric cancer including Japanese classification and WHO classification. The main two types are intestinal type adenocarcinoma and diffuse type adenocarcinoma.

Physiology of gastric acid secretion

Pathophysiology of gastric cancer

The pathophysiology of gastric cancer is based on various factors leading to decreased apoptosis, increased proliferation and abnormal differentiation of gastric epithelial cells. The following etiological factors contribute to the development of gastric cancer:[5]

Pathogenesis of intestinal type gastric cancer

Molecular effect of H.pylori:

Beta-catenin/Wnt signaling


Pathogenesis of diffuse-type gastric cancer

Apoptosis pathway

Neutrophil activation 

Apoptotic pathways


Helicobacter pylori infection
Inflammatory response
secretes IL-8 ,IL-1b
Production of
alkaline ammonia
Production of urease
bacterial phospholipase A
Infux of neutophils and macrophages
release of lysosomal enzymes
leukotrienes (LT)and
reactive oxygen
inhibition of D-cells
leads to inappropriate release of somatostatin
and hypergastrinemia
Production of urease
A and C
release toxic metabolities
Mucosal injury


Mutations of the following genes may lead to the development of gastric cancer:


Tumor suppressor genes

Cell cycle regulatory molecules

Epigenetic events


Associated Disorders

Familial predisposition

Hereditary diffuse gastric cancer[33]

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS)

Familial intestinal gastric cancer (FIGC)

Other hereditary cancer syndromes:[37]

Gross Pathology

The gross pathological findings in gastric cancer may be classified into the following types based on appearance of the tumor:

Type Description
Type 0  (superficial) typical of T1 tumors
Type 1 (mass) polypoid tumors sharply demarcated from the

surrounding mucosa

Type 2 (Ulcerative) ulcerated tumors with raised margins

surrounded by a thickened gastric wall with

clear margins

Type 3 (Infiltrative ulcerative) ulcerated tumors with raised margins,

surrounded by a thickened gastric wall

without clear margins

Type 4 (Diffuse infiltrative)

Tumors without marked ulceration or raised

margins, the gastric wall is thickened and

indurated and the margin is unclear

Type 5 (Unclassifiable)

Tumors that cannot be classified into any of the

above types

Video Showing Growth Pathology Of Gastric Cancer


Image shows gastric adenocarcinoma linitis plastica, source: Case courtesy of Dr Andrew Ryan,, rID: 16159


World Health Organization histological classification of gastric tumors:

Types Histological features
Epithelial tumors
Non-epithelial tumors
Malignant lymphomas

Japanese histological classification of gastric tumors:

Types Histological features
Epithelial tumors
Benign epithelial tumor
Malignant epithelial tumor

(Common types)

Special types
Miscellaneous carcinoma
Adrenocortical carcinoma,source: Public Domain,
signet ring appearance gastric cancer, source: CC BY-SA 3.0,

Video shows microscopic pathology of gastric cancer {{#ev:youtube|lRvq1fEW8sY}} {{#ev:youtube|lWeECaiEfSs}}


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