J Korean Gastric Cancer Assoc.  2008 Dec;8(4):169-175.

The Relation between Microsatellite Instability and the Thymidylate Synthase Expression in Gastric Cancer

Affiliations
  • 1Department of Surgery, College of Medicine, Pochon CHA University, Seongnam, Korea. dhahn@cha.ac.kr
  • 2Department of Pathology, College of Medicine, Pochon CHA University, Seongnam, Korea.
  • 3Department of Internal Medicine, College of Medicine, Pochon CHA University, Seongnam, Korea.

Abstract

PURPOSE: The main target of 5-fluorouracil (5-FU) is thymidylate synthase (TS). A high TS expression has been identified as promoting resistance to 5-FU. For colorectal cancers, the response to 5-FU based adjuvant chemotherapy is different according to the microsatellite instability (MSI) status. The reports on the relationship between MSI and the TS expression in colorectal cancer have been inconsistent. No data is available for gastric cancer regarding the relationship between MSI and the TS expression. Therefore, we studied the relationship between MSI and the TS expression in gastric cancer.
MATERIALS AND METHODS
Ninety-nine consecutive patients who underwent radical gastrectomy for gastric cancer from January 2004 to May 2006 at Bundang CHA hospital were studied. MSI was assessed for five markers (BAT25, BAT26, D2S123, D5S346, and D17S250) by PCR and with using an ABI prism 3100 Genetic analyzer. The TS expression was analyzed by immunohistochemistry with using mouse anti-thymidylate synthase monoclonal antibody to the TS 106 clone.
RESULTS
Out of the ninety-nine patients, MSS/MSI-L was detected in 92 (92.1%) cases and 7 cases (7.1%) were MSI-H. A negative TS expression was found in 46 (46.5%) cases, a low TS expression was found in 33 (33.3%) and a high TS expression was found in 20 (20.2%). Out of 92 MSS/MSI-L patients, the number of patients with negative, low and high TS expressions were 46 (50%), 30 (32.6%) and 16 (17.4%), respectively. Out of the 7 MSI-H patients, the number of patients with negative, low and high TS expressions were 0 (0%), 3 (42.9%) and 4 (57.1%), respectively. The relationship between MSI-H and a high TS expression was statistically significant.
CONCLUSION
Gastric cancer with MSI-H showed higher levels of a TS expression compared to the gastric cancer with MSS/MSI-L.

Keyword

Microsatellite instability; Thymidylate synthase; Gastric cancer

MeSH Terms

Animals
Chemotherapy, Adjuvant
Colorectal Neoplasms
Fluorouracil
Gastrectomy
Humans
Immunohistochemistry
Mice
Microsatellite Instability
Microsatellite Repeats
Polymerase Chain Reaction
Stomach Neoplasms
Succinimides
Thymidylate Synthase
Fluorouracil
Succinimides
Thymidylate Synthase
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