Affiliations: Department of Gastroenterological Surgery and Surgical
Oncology, Okayama University Graduate School of Medicine and Dentistry, Okayama
700-8558, Japan
Note: [] Address for correspondence and reprint request to: Dr. Nagahide
Matsubara, Department of Gastroenterological Surgery and Surgical Oncology,
Okayama University Graduate School of Medicine and Dentistry, 2-5-1
Shikata-cho, Okayama 700-8558, Japan. Tel.: +81 86 235 7257; Fax: +81 86 221
8775; E-mail: [email protected]
Abstract: Colorectal cancer (CRC) due to mismatch repair (MMR) defect has
distinct characteristics among unselected CRCs. These CRCs are biologically
less aggressive and, thus, showing better prognosis but less sensitive to the
5FU-based chemotherapy. CRCs with MMR defect derive from both hereditary and
sporadic reasons. Germline inactivation of MMR genes (hMLH1, hMSH2, hMSH6, and
hPMS2) underlies the hereditary CRC with MMR defect (Lynch syndrome) and
epigenetic silencing of hMLH1 gene causes the sporadic CRC with MMR defect.
Hereditary and sporadic CRC with MMR defect can be detectable by microsatellite
instability (MSI) test or immunohistochemical analysis among general CRCs.
Lynch syndrome can be diagnosed by the clinical criteria or by genetic test to
detect pathogenic germline mutations in MMR genes. However, both clinical
criteria and genetic test are inadequate for the diagnosis of Lynch syndrome.
Since genetic test for the diagnosis of the Lynch syndrome is expensive and not
always identify pathogenic germline mutations, effective and inexpensive
screening program is desirable. Here we propose a possible application of
methylation test combined with MSI or pathological analysis as an effective and
a cost-saving new strategy for screening of Lynch syndrome.
