| 摘要 |
The Lynch syndrome, (also as hereditary nonpolyposis colorectal cancer) is an
autosomal dominant disease, caused by germline mutations in four mismatch repair
(MMR) genes (MSH2, MLH1, PMS2, and MSH6), most notably MLH1 or MSH2,
Tumors caused by loss of mismatch repair gene function exhibit frequent errors in
microsatellite DNA, short segments of DNA containing 1~6 repeats of nucleotides,
and are thus said to exhibit microsatellite instability (MSI). Ninety percent of colon
cancers associated with Lynch syndrome show MSI, while only 15% sporadic CRCs
have MSI, caused mainly by hypermethylation of MLH1 promoter. Unlike familial
adenomatous polyposis, clinical features of the Lynch syndrome are not so unique.
However, the Lynch syndrome could be suspected at a relatively early age at onset of
CRC, on account of a higher incidence of synchronous and metachronous CRCs, a
predilection for the proximal colon, and specific pathologic findings including
tumor-infiltrating lymphocytes, signet ring cells, or a strong mucinous component.
Although the Lynch syndrome accounts for only 2 to 5% of all colorectal cancer
patients, the identification of this syndrome is clinically relevant. Aggressive
surveillance including colonoscopy for patients with Lynch syndrome and their
relatives could prevent cancer development and reduce mortality.
Currently, patients fulfilling the Amsterdam II/Revised Bethesda criteria are
suggested to receive MSI and/or IHC analysis of the tumor. Mutation analysis should
be offered in those with evidence of MSI or loss of MMR expression. |
