{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T09:47:18Z","timestamp":1761126438952,"version":"build-2065373602"},"reference-count":37,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2002,4,25]],"date-time":"2002-04-25T00:00:00Z","timestamp":1019692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Swedish Cancer Fund"},{"name":"G.A.E. Nilsson Cancer Fund"},{"name":"King Gustaf's Jubilee Fund"},{"name":"Minerva Fund"},{"name":"Kamprad Cancer Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Patients with the familial syndrome hereditary nonpolyposis colorectal carcinoma (HNPCC) exhibit an increased risk for several tumor types, of which the greatest lifetime risk is for colorectal and endometrial carcinoma. HNPCC is caused by a germline mutation in one of several identified mismatch repair (MMR) genes and typically presents with microsatellite instability (MSI) and frequent loss of MMR protein expression in the tumor tissue. The objective of this study was to estimate the proportion of double primary tumors of the endometrium and colorectum that displays tumor characteristics suggestive of MMR deficiency.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The authors used the southern Sweden regional population\u2010based Cancer Registry to identify women who developed double primary tumors of the endometrium and colorectum. Of the 256 women who were diagnosed with carcinoma at both of these sites during the period 1958\u20131998, 39 women had developed their first tumor before age 50 years. The authors successfully retrieved 67 tumors from 36 of these patients and analyzed them for MSI and immunohistochemical expression of the MMR genes, <jats:italic>MLH1<\/jats:italic>, <jats:italic>MSH2<\/jats:italic>, and <jats:italic>MSH6<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The MSI status of the 67 tumors was high MSI in 37 tumors, low MSI in 13 tumors, and microsatellite stable (MSS) in 17 tumors. Immunohistochemical loss of MMR protein expression was correlated with MSI status and was demonstrated in 29 high MSI tumors, in 1 low MSI tumor, and in 1 MSS tumor. A concordant loss of the same MMR protein in both tumors was found in 12 of 27 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The authors demonstrated a high frequency of MSI (75%) in tumors from women with endometrial and colorectal carcinoma who had their first tumor diagnosed before age 50 years and observed concordant immunohistochemical loss of MMR protein expression, suggestive of a possible underlying germline mutation, in 12 of 27 patients (44%). They concluded that double primary malignancies of the colorectum and endometrium at a young age should make the clinician suspect HNPCC. Cancer 2002; 94:2502\u201310. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.10501<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.10501","type":"journal-article","created":{"date-parts":[[2004,10,27]],"date-time":"2004-10-27T03:57:47Z","timestamp":1098849467000},"page":"2502-2510","source":"Crossref","is-referenced-by-count":28,"title":["High frequency of microsatellite instability and loss of mismatch\u2010repair protein expression in patients with double primary tumors of the endometrium and colorectum"],"prefix":"10.1002","volume":"94","author":[{"given":"Maria","family":"Planck","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Rambech","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela","family":"M\u00f6slein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfram","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e5kan","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mef","family":"Nilbert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,4,25]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990412)81:2<214::AID-IJC8>3.0.CO;2-L"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70510-X"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9322509"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.12.1433"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8484121"},{"issue":"21","key":"e_1_2_6_7_2","first-page":"5100","article-title":"Genetic instability of microsatellites in endometrial carcinoma","volume":"53","author":"Risinger JI","year":"1993","journal-title":"Cancer Res."},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199805213382101"},{"issue":"8","key":"e_1_2_6_9_2","first-page":"1713","article-title":"Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1","volume":"58","author":"Thibodeau SN","year":"1998","journal-title":"Cancer Res."},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(00)80250-6"},{"issue":"23","key":"e_1_2_6_11_2","first-page":"5556","article-title":"Mutations in DNA mismatch repair genes are not responsible for microsatellite instability in most sporadic endometrial carcinomas","volume":"55","author":"Katabuchi H","year":"1995","journal-title":"Cancer Res."},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0195-48"},{"issue":"11","key":"e_1_2_6_13_2","first-page":"1907","article-title":"Absence of mutations in DNA mismatch repair genes in sporadic endometrial tumors with microsatellite instability","volume":"2","author":"Lim PC","year":"1996","journal-title":"Clin Cancer Res."},{"issue":"5","key":"e_1_2_6_14_2","first-page":"808","article-title":"Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair\u2010defective human tumor cell lines","volume":"57","author":"Kane MF","year":"1997","journal-title":"Cancer Res."},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1202178"},{"issue":"6","key":"e_1_2_6_16_2","first-page":"411","article-title":"A population\u2010based study of endometrial cancer and familial risk in younger women. 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