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Prospective assessment of microsatellite instability in gastrointestinal neoplasia in Ashkenazi and non-Ashkenazi Jews.
J Med. 2003; 34(1-6):139-48.JM

Abstract

BACKGROUND

Microsatellite instability (MSI) is a useful marker of replication errors in neoplasia, resulting from mutations in the mismatch repair (MMR) genes. Nearly all hereditary non-polyposis colorectal cancer (HNPCC) and about 15% of sporadic colorectal cancers (CRC) exhibit high MSI (MSI-H). The use of the Amsterdam criteria for HNPCC diagnosis may fail to identify many HNPCC cases. Genetic screening of mutations in the MMR genes is laborious, time-consuming, expensive and limited by a low detection rate. Hence, MSI testing is a feasible and cost-effective method to select suspected HNPCC patients for genetic analysis. MSI has not been used routinely or prospectively in the assessment of newly diagnosed CRC.

AIMS

To prospectively evaluate MSI status in a cohort of patients seen at the Gastrointestinal Oncology Unit of the Tel Aviv Medical Center.

METHODS

Ninety-eight consecutive patients with colonic or gastric neoplasia were included. Samples from neoplastic and normal mucosa were obtained at the time of diagnostic endoscopy. MSI was determined based on five Bethesda markers using standard polymerase chain reaction procedures.

RESULTS

The overall incidence of MSI was 20.4%. MSI-H was detected in 22.2% of CRC, 20% of colonic adenomas and 18.2% of gastric neoplasia. MSI-positive neoplasia tended to display multiple colonic sites, moderate-well differentiated tumors, and a higher rate of familial gastrointestinal neoplasia.

CONCLUSIONS

MSI may be involved in the early stages of some colorectal tumorigenesis pathways since it may be detected in adenomas. MSI may serve as a cost-effective, reliable and important tool in the selection of HNPCC-suspected families for genetic testing. A small study population, referral bias or ethnic variation might explain the higher MSI rate. It is suggested that, similar to familial adenomatous polyposis, a state of attenuated HNPCC may exist. Hence, the clinical approach in positive patients, and their family members, should be conducted as for families with genetically proven HNPCC.

Authors+Show Affiliations

Gastrointestinal Oncology Unit, Department of Gastroenterology, Tel Aviv Sourasky Medical Center, Ramat Aviv, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17682319

Citation

Strul, H, et al. "Prospective Assessment of Microsatellite Instability in Gastrointestinal Neoplasia in Ashkenazi and non-Ashkenazi Jews." Journal of Medicine, vol. 34, no. 1-6, 2003, pp. 139-48.
Strul H, Liberman E, Kariv R, et al. Prospective assessment of microsatellite instability in gastrointestinal neoplasia in Ashkenazi and non-Ashkenazi Jews. J Med. 2003;34(1-6):139-48.
Strul, H., Liberman, E., Kariv, R., Gartner, M., Kazanov, D., Keidar, A., Carmeli, Y., Degani, Y., Halpern, Z., & Arber, N. (2003). Prospective assessment of microsatellite instability in gastrointestinal neoplasia in Ashkenazi and non-Ashkenazi Jews. Journal of Medicine, 34(1-6), 139-48.
Strul H, et al. Prospective Assessment of Microsatellite Instability in Gastrointestinal Neoplasia in Ashkenazi and non-Ashkenazi Jews. J Med. 2003;34(1-6):139-48. PubMed PMID: 17682319.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prospective assessment of microsatellite instability in gastrointestinal neoplasia in Ashkenazi and non-Ashkenazi Jews. AU - Strul,H, AU - Liberman,E, AU - Kariv,R, AU - Gartner,M, AU - Kazanov,D, AU - Keidar,A, AU - Carmeli,Y, AU - Degani,Y, AU - Halpern,Z, AU - Arber,N, PY - 2007/8/9/pubmed PY - 2007/9/22/medline PY - 2007/8/9/entrez SP - 139 EP - 48 JF - Journal of medicine JO - J Med VL - 34 IS - 1-6 N2 - BACKGROUND: Microsatellite instability (MSI) is a useful marker of replication errors in neoplasia, resulting from mutations in the mismatch repair (MMR) genes. Nearly all hereditary non-polyposis colorectal cancer (HNPCC) and about 15% of sporadic colorectal cancers (CRC) exhibit high MSI (MSI-H). The use of the Amsterdam criteria for HNPCC diagnosis may fail to identify many HNPCC cases. Genetic screening of mutations in the MMR genes is laborious, time-consuming, expensive and limited by a low detection rate. Hence, MSI testing is a feasible and cost-effective method to select suspected HNPCC patients for genetic analysis. MSI has not been used routinely or prospectively in the assessment of newly diagnosed CRC. AIMS: To prospectively evaluate MSI status in a cohort of patients seen at the Gastrointestinal Oncology Unit of the Tel Aviv Medical Center. METHODS: Ninety-eight consecutive patients with colonic or gastric neoplasia were included. Samples from neoplastic and normal mucosa were obtained at the time of diagnostic endoscopy. MSI was determined based on five Bethesda markers using standard polymerase chain reaction procedures. RESULTS: The overall incidence of MSI was 20.4%. MSI-H was detected in 22.2% of CRC, 20% of colonic adenomas and 18.2% of gastric neoplasia. MSI-positive neoplasia tended to display multiple colonic sites, moderate-well differentiated tumors, and a higher rate of familial gastrointestinal neoplasia. CONCLUSIONS: MSI may be involved in the early stages of some colorectal tumorigenesis pathways since it may be detected in adenomas. MSI may serve as a cost-effective, reliable and important tool in the selection of HNPCC-suspected families for genetic testing. A small study population, referral bias or ethnic variation might explain the higher MSI rate. It is suggested that, similar to familial adenomatous polyposis, a state of attenuated HNPCC may exist. Hence, the clinical approach in positive patients, and their family members, should be conducted as for families with genetically proven HNPCC. SN - 0025-7850 UR - https://www.unboundmedicine.com/medline/citation/17682319/Prospective_assessment_of_microsatellite_instability_in_gastrointestinal_neoplasia_in_Ashkenazi_and_non_Ashkenazi_Jews_ L2 - https://medlineplus.gov/stomachcancer.html DB - PRIME DP - Unbound Medicine ER -