GASTRIC CANCER Risk Factors And Pathology

GASTRIC CANCER
Risk Factors and Pathology
Antonia R. Sepulveda M.D., Ph.D.
Department of Pathology and Laboratory Medicine
University of Pennsylvania, Philadelphia, PA
asepu@mail.med.upenn.edu

STOMACH TUMORS
–Carcinoma
– Lymphoma (MALT; other)
– Gastrointestinal stromal tumors
(GIST)
– Leiomyoma; Leiomyosarcoma
– Carcinoid tumors

Gastric Cancer
LOCATION
Cardia
Fundus
Body
H. J. Stein, M. Feith and J. R. Siewert
Surgical Oncology, 9, (1) 35-41; 2000
Antrum
Pylorus

Stomach (Gastric) Cancer
• Overall 14th in incidence among the major
types of cancer in the US
• Worldwide, gastric cancer is the fourth most
common cancer
• Estimated new cases from stomach cancer in
the United States in 2008:
– New cases: 21,500

Stomach (Gastric) Cancer
• Age: Most people with this disease are 72 or older
(in the US).
• Sex: Men are more likely than women to develop
stomach cancer.
• Race: more common in Asian, Pacific Islander,
Hispanic, and African Americans than in non-
Hispanic white Americans.
• Conditions with increased risk of stomach cancer:
– Stomach surgery
– Chronic gastritis:
• Helicobacter pylori
• Autoimmune gastritis-Pernicious anemia

Role of Pathology and Pathologists in
evaluation of patients for gastric cancer
• Diagnosis: in biopsy
sample or surgically
resected stomach
• Determine tumor stage
• Precursor lesions
Intestinal metaplasia->
dysplasia
• Important for selection
of treatment
• Important for
surveillance &
prevention
• Contributing risk factors
or underlying cause
– H. pylori gastritis
– Genetic predisposition
(hereditary gastric cancer)
• Important for
prevention of cancer

Pathologic Types of Gastric Carcinoma
-Adenocarcinoma
Well or Moderately
Poorly Differentiated
Differentiated
Signet ring cell
Intestinal type
Diffuse

Signet Ring Cell Carcinoma:
Sporadic type or hereditary gastric cancer

Chronic
H. pylori
infection
Carcinogens
Smoking
Hereditary
E. cadherin
Mutation
Gastric
Cancer
Risk factors
Hereditary
HNPCC
FAP
Genetic
susceptibility
Salt
Nitrosamines
Low
Vitamin C

Facts:
-H. pylori infects 50% of the world population
-30–40% of the U.S. population is infected with
H. pylori

Helicobacter pylori Gastritis and
H. pylori
infection
Gastric Cancer
Chronic
Gastritis
Atrophy &
Intestinal
Metaplasia
Decades...
Dysplasia
Adenoma
Carcinoma

Gastric Intestinal Metaplasia
and Surveillance
• Extensive Atrophic gastritis and intestinal
metaplasia:
– 10 year surveillance 8.4% developed gastric cancer
– Recommend annual surveillance
-Whiting et al. Gut 2003;50:378-81

Treating H. pylori gastritis before and
after diagnosis of gastric cancer
• H. pylori gastritis is treated with antibiotics
• H. pylori eradication reduced the incidence of gastric
cancer in patients without atrophy or IM, suggesting
that eradication may contribute to preventing
progression to gastric cancer
– Wong et al. JAMA 291, 187-94, 2004
• Recent studies recommend prophylactic H. pylori
eradication after resection of early gastric cancer to
reduce the risk of carcinoma in the remnant stomach
Fukase et al. Japan Gast Study Group Lancet 372: 392–97, 2008

Familial Diffuse Gastric Cancer
• Associated with germline mutations in the E-
cadherin gene
– Genetic testing in blood DNA
• Autosomal dominant: Gastric cancer develops
in 3 of every four carriers of this mutation at
young age-often multifocal
• Genetic testing and consideration of
prophylactic gastrectomy recommended
• Pathology: diagnosis of characteristic signet
ring cell carcinomas.