J Korean Surg Soc.  2010 Aug;79(2):94-102. 10.4174/jkss.2010.79.2.94.

Overexpression of p53, Mutation of hMLH1 and Microsatellite Instability in Gastric Carcinomas: Clinicopathologic Implications and Prognosis

• Kwon J
• Lee JH
• Jee YS
• Park DJ
• Kim HH
• Lee HJ
• Yang HK
• Lee KU
• Lee HS

• KMID: 2211978
• DOI: http://doi.org/10.4174/jkss.2010.79.2.94

Abstract

PURPOSE
Mutated p53 is a tumor suppressor gene, hMLH1 is a mismatch repair gene, and hypermethylation of hMLH1 follows microsatellite instability (MSI). This research's aim is to investigate mutated p53, inactivated hMLH1 and MSI in gastric cancer and their clinicopathologic implications.
METHODS
Between 2003 and 2007, 618 patients underwent curative radical gastrectomy for gastric cancer at Seoul National University Bundang Hospital in Korea. We reviewed their medical charts and the pathologic reports with immunohistochemistry for p53, hMLH1 and polymerase chain reaction for MSI in 509, 499, and 561 cases, respectively. These genetic markers were statistically compared with clinicopathologic features and postoperative survival.
RESULTS
The expression ratios of mutated p53, inactivated hMLH1, and MSI were 32.8%, 8.4%, and 8.7%, respectively. Mutation of p53 occurred more frequently in aged group (over 40), differentiated group (against the non-differentiated group), intestinal type, infiltrative type and positive lymph node metastasis group. Inactivated hMLH1 occurred more frequently in aged group, differentiated group, intestinal type and expanding growth type group. MSI was found more frequently in aged group, intestinal type and expanding growth type group. All three genetic markers had no significant associations with the 5-year survival.
CONCLUSION
We identified significant relationships between mutated p53, inactivated hMLH1, and MSI with some clinicopathologic features of gastric cancer. However, there were no apparent relationships between p53, hMLH1, and MSI and prognosis.

Keyword

Gastric cancer; p53; hMLH1; Microsatellite instability; Carcinogenesis

MeSH Terms

Aged
DNA Mismatch Repair
Gastrectomy
Genes, Tumor Suppressor
Genetic Markers
Humans
Immunohistochemistry
Korea
Lymph Nodes
Microsatellite Instability
Microsatellite Repeats
Neoplasm Metastasis
Polymerase Chain Reaction
Prognosis
Stomach Neoplasms
Succinimides
Genetic Markers
Succinimides

Figure

• 

  Fig. 1 Immunohistochemical detection of overexpression of p53 (×400) (A). A gastric cancer case with complete loss of the protein in the invasive part (Left field) and preserved hMLH1 expression in adjacent normal tissue (Right field) (×400) (B).

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  Fig. 2 Cumulative 5-year survival rates in 509 patients with gastric cancer according to the p53 expression. There is no statistically significant difference of overall cumulative 5-year survival rates between p53(+) group and p53(-) group (P=0.807).

• 

  Fig. 3 Cumulative 5-year survival rates in 499 patients with gastric cancer according to the hMLH1 activation. There is no statistically significant difference of overall cumulative 5-year survival rates between inactivated hMLH1 group and activated hMLH1 group (P=0.988).

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  Fig. 4 Cumulative 5-year survival rates in 561 patients with gastric cancer according to the MSI expression. There is no statistically significant difference of overall cumulative 5-year survival rates between microsatellite instable group and microsatellite stable group (P=0.833). MSS = microsatellite stable, MSI = microsatellite instable.

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