J Gastric Cancer.  2010 Dec;10(4):149-154.

Microsatellite Instability Is Associated with the Clinicopathologic Features of Gastric Cancer in Sporadic Gastric Cancer Patients

Affiliations
  • 1Department of Surgery, Hanyang University College of Medicine, Seoul, Korea. leekh@hanyang.ac.kr
  • 2Department of Pathology, Hanyang University College of Medicine, Seoul, Korea.

Abstract

PURPOSE
Replication error is an important mechanism in carcinogenesis. The microsatellite instability (MSI-H) of colorectal cancers is associated with the development of multiple cancers. The influence of MSI-H on the development of multiple gastric cancers in sporadic gastric cancer patients has not been defined. This study was performed to reveal the association between the clinicopathologic features and MSI in sporadic gastric cancers.
MATERIALS AND METHODS
Between July 2004 and March 2009, the clinicopathologic characteristics, including MSI status, were evaluated in 128 consecutive patients with sporadic gastric cancers. None of the patients had hereditary non-polyposis colorectal cancer of familial gastric cancer. The markers that were recommended by the NCI to determine the MSI status for colorectal cancers were used.
RESULTS
MSI-H cancers were found in 10.9% of the patients (14/128). Synchronous gastric cancers were shown in 4 patients (3.1%). Synchronous cancers were found in 2 of 14 patients with MSI-H gastric cancer (14.3%) and 2 of 114 patients with MSS gastric cancer (1.8%; P=0.059, Fisher's exact test). Among the patients with synchronous cancer 50% (2/4) had MSI-H cancer, but 9.7% of the patients (12/124) without synchronous cancer had MSI-H cancer. MSI-H (RR, 24.7; 95% CI, 1.5~398.9; P=0.024) was related with to synchronous gastric cancer, but age, gender, family history, histologic type, location, gross morphology, size, and stage were not related to synchronous gastric cancer.
CONCLUSIONS
MSI is associated with the intestinal-type gastric cancer and the presence of multiple gastric cancers in patients with sporadic gastric cancer. Special attention to the presence of synchronous and the development of metachronous multiple cancer in patients with MSI-H gastric cancer is needed.

Keyword

Microsatellite instability; Stomach neoplasms; Synchronous gastric cancer

MeSH Terms

Colorectal Neoplasms
Humans
Microsatellite Instability
Microsatellite Repeats
Stomach Neoplasms
Succinimides
Succinimides

Figure

  • Fig. 1 An example of PCR analysis of microsatellite instability. Tumor DNA shows alterations of allele lengths in BAT25, BAT26, D5S346, D2S123, and D17S250. ▾ = arrow heads indicate microsatellite instability. Microsatellite instability is associated with the clinicopathologic features of gastric cancer in sporadic gastric cancer patients.


Reference

1. Pedroni M, Tamassia MG, Percesepe A, Roncucci L, Benatti P, Lanza G Jr, et al. Microsatellite instability in multiple colorectal tumors. Int J Cancer. 1999; 81:1–5. PMID: 10077143.
Article
2. Sengupta SB, Yiu CY, Boulos PB, De Silva M, Sams VR, Delhanty JD. Genetic instability in patients with metachronous colorectal cancers. Br J Surg. 1997; 84:996–1000. PMID: 9240146.
Article
3. Bae JM, Won YJ, Jung KW, Suh KA, Ahn DH, Park JG. Annual report of the central cancer registry in Korea-1999: based on registered data from 128 hospitals. Cancer Res Treat. 2001; 33:367–372.
Article
4. Honmyo U, Misumi A, Murakami A, Haga Y, Akagi M. Clinicopathological analysis of synchronous multiple gastric carcinoma. Eur J Surg Oncol. 1989; 15:316–321. PMID: 2547661.
5. Kaibara N, Maeta M, Ikeguchi M. Patients with multiple primary gastric cancers tend to develop second primaries in organs other than the stomach. Surg Today. 1993; 23:186–188. PMID: 8467167.
Article
6. Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, et al. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology. 1993; 104:1535–1549. PMID: 8482467.
Article
7. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma - 2nd english edition -. Gastric Cancer. 1998; 1:10–24. PMID: 11957040.
8. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a HISTO-clinical classification. Acta Pathol Microbiol Scand. 1965; 64:31–49. PMID: 14320675.
9. Cleary JB, Kazarian KK, Mersheimer WL. Multiple primary cancer. Thirty patients with three or more primary cancers. Am J Surg. 1975; 129:686–690. PMID: 1130613.
10. Suraweera N, Duval A, Reperant M, Vaury C, Furlan D, Leroy K, et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology. 2002; 123:1804–1811. PMID: 12454837.
Article
11. Boland CR, Thibodeau SN, Hamilton SR, Sidransky D, Eshleman JR, Burt RW, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 1998; 58:5248–5257. PMID: 9823339.
12. Ahn YJ, Oh SJ, Song JW, Kang WH, Hyung WJ, Choi SH, et al. The clinicopathologic features and prognosis of multiple early gastric cancer. J Korean Gastric Cancer Assoc. 2008; 8:198–203.
Article
13. Ribeiro U Jr, Jorge UM, Safatle-Ribeiro AV, Yagi OK, Scapulatempo C, Perez RO, et al. Clinicopathologic and immunohistochemistry characterization of synchronous multiple primary gastric adenocarcinoma. J Gastrointest Surg. 2007; 11:233–239. PMID: 17458592.
Article
14. Bae JS, Lee JH, Ryu KW, Kim YW, Bae JM. Characteristics of synchronous cancers in gastric cancer patients. Cancer Res Treat. 2006; 38:25–29. PMID: 19771255.
Article
15. Tahara E. Molecular mechanism of stomach carcinogenesis. J Cancer Res Clin Oncol. 1993; 119:265–272. PMID: 8440743.
Article
16. Chong JM, Fukayama M, Hayashi Y, Takizawa T, Koike M, Konishi M, et al. Microsatellite instability in the progression of gastric carcinoma. Cancer Res. 1994; 54:4595–4597. PMID: 8062248.
17. Sepulveda AR, Santos AC, Yamaoka Y, Wu L, Gutierrez O, Kim JG, et al. Marked differences in the frequency of microsatellite instability in gastric cancer from different countries. Am J Gastroenterol. 1999; 94:3034–3038. PMID: 10520865.
Article
18. Lim S, Lee HS, Kim HS, Kim YI, Kim WH. Alteration of E-cadherin-mediated adhesion protein is common, but microsatellite instability is uncommon in young age gastric cancers. Histopathology. 2003; 42:128–136. PMID: 12558744.
Article
19. Hayden JD, Cawkwell L, Quirke P, Dixon MF, Goldstone AR, Sue-Ling H, et al. Prognostic significance of microsatellite instability in patients with gastric carcinoma. Eur J Cancer. 1997; 33:2342–2346. PMID: 9616279.
Article
20. Nakashima H, Inoue H, Honda M, Shibuta K, Arinaga S, Mori M, et al. The heterogeneity of microsatellite instability in multiple gastric cancers. Am J Gastroenterol. 1995; 90:653–656. PMID: 7717330.
21. Oliveira C, Seruca R, Seixas M, Sobrinho-Simões M. The clinicopathological features of gastric carcinomas with microsatellite instability may be mediated by mutations of different "target genes": a study of the TGFbeta RII, IGFII R, and BAX genes. Am J Pathol. 1998; 153:1211–1219. PMID: 9777952.
22. Miyoshi E, Haruma K, Hiyama T, Tanaka S, Yoshihara M, Shimamoto F, et al. Microsatellite instability is a genetic marker for the development of multiple gastric cancers. Int J Cancer. 2001; 95:350–353. PMID: 11668515.
Article
23. Kodera Y, Yamamura Y, Torii A, Uesaka K, Hirai T, Yasui K, et al. Incidence, diagnosis and significance of multiple gastric cancer. Br J Surg. 1995; 82:1540–1543. PMID: 8535813.
Article
24. Kim HC, Roh SA, Yook JH, Oh ST, Kim BS, Yu CS, et al. Microsatellite instability and promoter methylation of hMLH1 in sporadic gastric carcinoma. J Korean Gastric Cancer Assoc. 2003; 3:50–55.
Article
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