{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:24:14Z","timestamp":1790868254939,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,10,10]],"date-time":"2001-10-10T00:00:00Z","timestamp":1002672000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2001,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Ki\u2010<jats:italic>ras<\/jats:italic> mutations are associated with an increased risk of relapse and death in colorectal cancer (CRC) patients, with some mutations being more aggressive than others. The present study examined the predictive value of different Ki\u2010<jats:italic>ras<\/jats:italic> mutation types in a retrospective series of 430 Dukes' C stage CRC patients, of whom 208 (48%) had received adjuvant chemotherapy with 5\u2010fluorouracil\/levamisole or 5\u2010fluorouracil\/leucovorin. A total of 140 mutations were detected, the majority (58%, 81\/140) being glycine to aspartate mutations in codons 12 and 13. Glycine to valine mutations in codon 12 (14%, 20\/140) and other less frequent, non\u2010specified mutation types (28%, 39\/140) accounted for the remaining mutations. Kaplan\u2013Meier survival analysis revealed that both Ki\u2010<jats:italic>ras<\/jats:italic> wild\u2010type and mutant patient groups derived significant survival benefit from chemotherapy. However, when patients were stratified according to the type of mutation, those with non\u2010aspartate mutations appeared to gain more benefit from this treatment than those with aspartate mutations. Multivariate analysis that included other possible predictive factors in Dukes' C CRC (tumour site, patient sex, <jats:italic>TP53<\/jats:italic> mutation) demonstrated that non\u2010aspartate mutations in particular were associated with a significant survival benefit from chemotherapy (HR=0.11, 95% CI: 0.04\u20130.30, <jats:italic>p<\/jats:italic>&lt;0.001). These results suggest that the type of Ki\u2010<jats:italic>ras<\/jats:italic> mutation could be a clinically useful molecular marker for the identification of CRC subgroups that are likely to benefit from 5\u2010fluorouracil\u2010based adjuvant chemotherapy. Copyright \u00a9 2001 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.990","type":"journal-article","created":{"date-parts":[[2002,8,25]],"date-time":"2002-08-25T12:15:26Z","timestamp":1030277726000},"page":"543-548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Ki\u2010<i>ras<\/i> mutation type and the survival benefit from adjuvant chemotherapy in Dukes' C colorectal cancer"],"prefix":"10.1002","volume":"195","author":[{"given":"G.","family":"Gnanasampanthan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Elsaleh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"McCaul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Iacopetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,10,10]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"4682","article-title":"Ras oncogenes in human cancer: a review","volume":"49","author":"Bos JL","year":"1989","journal-title":"Cancer Res"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198809013190901"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/90.9.675"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199806)185:2<130::AID-PATH85>3.0.CO;2-M"},{"key":"e_1_2_6_6_2","first-page":"411","article-title":"Detection of K\u2010ras mutations in lung carcinomas \u2013 relationship to prognosis","volume":"2","author":"Keohavong P","year":"1996","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199903)187:4<433::AID-PATH273>3.0.CO;2-E"},{"key":"e_1_2_6_8_2","first-page":"5217","article-title":"TP53 point mutation and survival in colorectal cancer patients","volume":"55","author":"Goh H","year":"1995","journal-title":"Cancer Res"},{"key":"e_1_2_6_9_2","first-page":"203","article-title":"TP53 and long\u2010term prognosis in colorectal cancer: mutations in the L3 zinc\u2010binding domain predict poor survival","volume":"4","author":"Borresen\u2010Dale AL","year":"1998","journal-title":"Clin Cancer Res"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3277276"},{"key":"e_1_2_6_11_2","first-page":"793","article-title":"Increased resistance to cis\u2010diamminedichloroplatinum(I) in NIH 3T3 cells transformed by ras oncogenes","volume":"48","author":"Sklar M","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_6_12_2","first-page":"441","article-title":"Mutant K\u2010ras oncogenes in colon cancers do not predict patient's chemotherapy response or survival","volume":"1","author":"Markowitz S","year":"1995","journal-title":"Clin Can Res"},{"key":"e_1_2_6_13_2","first-page":"1149","article-title":"Ki\u2010ras mutation and p53 overexpression predict the clinical behaviour of colorectal cancer: a Southwest Oncology Group study","volume":"58","author":"Ahnen DJ","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-122-5-199503010-00001"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02261-3"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/363558a0"},{"key":"e_1_2_6_17_2","first-page":"501","article-title":"Aberrant methylation of p16INK4a in anatomic and gender\u2010specific subtypes of sporadic colorectal cancer","volume":"8","author":"Wiencke JK","year":"1999","journal-title":"Cancer Epidemiol Biomarkers Prevention"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-8049(00)00285-9"},{"key":"e_1_2_6_19_2","first-page":"252","article-title":"A rapid and non\u2010isotopic method for the screening and sequencing of TP53 gene mutations in formalin\u2010fixed, paraffin\u2010embedded tumours","volume":"10","author":"Soong R","year":"1997","journal-title":"Mod Pathol"},{"key":"e_1_2_6_20_2","first-page":"361","article-title":"Methods in laboratory investigation. 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