{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T04:49:07Z","timestamp":1768279747978,"version":"3.49.0"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T00:00:00Z","timestamp":1053993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Minnesota Medical Foundation","award":["SMF-2035-98"],"award-info":[{"award-number":["SMF-2035-98"]}]},{"DOI":"10.13039\/100003133","name":"Minnesota Colon and Rectal Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100003133","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>A small proportion of patients with colorectal carcinoma (CRC) have synchronous tumors at the time of diagnosis. A subset of sporadic CRCs display microsatellite instability (MSI) that is associated with <jats:italic>MLH1<\/jats:italic> silencing due to promoter methylation. In the current study, the authors investigated the proportion of tumors with MSI in patients with synchronous colorectal carcinoma (SCRC) and the concordance in MSI status among tumors in a given individual. In addition, the authors examined MLH1 and MSH2 expression and <jats:italic>MLH1<\/jats:italic> promoter methylation in SCRCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The current study included 77 patients, with a combined total of 170 invasive SCRCs, who were identified from a database of 2884 patients with CRC. Instability was determined by polymerase chain reaction (PCR) amplification using a set of five markers. Tumors that were unstable at two or more markers were considered unstable (MSI); otherwise, they were considered microsatellite stable (MSS). Expression of MLH1 and MSH2 was determined by immunohistochemistry. Methylation of the <jats:italic>MLH1<\/jats:italic> gene promoter was determined by a methylation\u2010specific PCR assay. Statistical comparisons were made using the chi\u2010square test or the Student <jats:italic>t<\/jats:italic> test.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Of the 77 patients in the study, 21 (27%) had a family history of hereditary nonpolyposis colon carcinoma\u2013related malignancy, but none fulfilled the Amsterdam II criteria. Fifty\u2010four of 170 tumors (32%) were found to be MSI. Patients with MSI tumors were older and more frequently female. All but 1 MSI tumor lacked expression of MLH1 (<jats:italic>n<\/jats:italic> = 44) or MSH2 (<jats:italic>n<\/jats:italic> = 8), or both (<jats:italic>n<\/jats:italic> = 1). All MLH1\u2010negative tumors, compared with only 3 MLH1\u2010positive tumors, were methylated at the <jats:italic>MLH1<\/jats:italic> promoter. Most patients (<jats:italic>n<\/jats:italic> = 67; 87%) had either all MSS tumors (<jats:italic>n<\/jats:italic> = 48; 62%) or all MSI tumors (<jats:italic>n<\/jats:italic> = 19; 25%); 10 patients (13%) had both MSS and MSI tumors. The observed MSI\/MSS distribution was significantly different from the distribution expected based on an assumption of independence (<jats:italic>P<\/jats:italic> &lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>There is a strong concordance in MSI\/MSS status among tumors in the same individual. This finding suggests that the tumors in patients with SCRC develop along a preferred molecular pathway. Cancer 2003;98:48\u201354. \u00a9 2003 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.11445<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.11445","type":"journal-article","created":{"date-parts":[[2003,6,23]],"date-time":"2003-06-23T12:15:02Z","timestamp":1056370502000},"page":"48-54","source":"Crossref","is-referenced-by-count":29,"title":["Evidence of a preferred molecular pathway in patients with synchronous colorectal cancer"],"prefix":"10.1002","volume":"98","author":[{"given":"Sharon L.","family":"Dykes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongming","family":"Qui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David 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