{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:59:19Z","timestamp":1775267959189,"version":"3.50.1"},"reference-count":49,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"21","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,7,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Hereditary nonpolyposis colorectal cancer (HNPCC) may be caused by mutations in mismatch repair (MMR) genes. The aim of this study was to validate immunohistochemistry and family history as prescreening tools to predict germline mutations in MLH1, MSH2, and MSH6. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Pedigrees from 250 families were extended, cancer diagnoses were verified, and families were classified according to the Amsterdam and the Bethesda criteria. Tumor specimens were examined with immunohistochemistry for the presence of MLH1, MSH2, and MSH6 proteins. Mutation analyses were performed in blood samples from the same patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Blood samples from affected index persons in 181 families and tumor specimens from 127 of the affected index persons were obtained. Thirty tumors lacked one or more gene products. Sensitivity of immunohistochemistry to detect mutation carriers was 100%, specificity was 82%, and positive predictive value was 85%. Sensitivities, specificities, and positive predictive values for the Amsterdam criteria were 82%, 8%, and 45%, respectively, and for the Bethesda criteria were 100%, 0%, and 48%, respectively. Distribution of mutations was MLH1 = 4, MSH2 = 11, and MSH6 = 4. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Wide clinical criteria to select HNPCC kindreds, followed by immunohistochemistry of tumor material from one affected person in each family, had high sensitivity and specificity to predict MMR mutations. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.05.180","type":"journal-article","created":{"date-parts":[[2005,7,20]],"date-time":"2005-07-20T23:55:03Z","timestamp":1121903703000},"page":"4705-4712","source":"Crossref","is-referenced-by-count":30,"title":["Immunohistochemistry Identifies Carriers of Mismatch Repair Gene Defects Causing Hereditary Nonpolyposis Colorectal Cancer"],"prefix":"10.1200","volume":"23","author":[{"given":"Astrid T.","family":"Stormorken","sequence":"first","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inger Marie","family":"Bowitz-Lothe","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tove","family":"Nor\u00e8n","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elin","family":"Kure","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steinar","family":"Aase","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juul","family":"Wijnen","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaran","family":"Apold","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ketil","family":"Heimdal","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e5l","family":"M\u00f8ller","sequence":"additional","affiliation":[{"name":"From the Section of Genetic Counselling, Department of Cancer Genetics, The Norwegian Radium Hospital; Department of Pathology, Ullev\u00e5l University Hospital, Oslo; Department of Occupational and Environmental Medicine, Telemark Hospital, Skien; Telemark University College, B\u00f8; Center of Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.1992.tb01136.x"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(00)70168-5"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1007\/BF02053699"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2001.26265"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91016-6"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.1977.01370020064007"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1136\/gut.33.6.783"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.agast960943"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1996.v110.agast960943"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1054\/drup.1999.0099"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(99)70510-X"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/89.23.1758"},{"key":"R13","unstructured":"Boland CR, Thibodeau SN, Hamilton SR, et al: A National Cancer Institute workshop on microsatellite instability for cancer detection and familial predisposition: Development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248,1998-5257,"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH701>3.0.CO;2-2"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1038\/365274a0"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90546-3"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90330-S"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1038\/368258a0"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1126\/science.8128251"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1038\/13773"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1038\/371075a0"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9322509"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Viel A, Novella E, Genuardi M, et al: Lack of PMS2 gene-truncating mutations in patients with hereditary colorectal cancer. Int J Oncol 13:565,1998-569,","DOI":"10.3892\/ijo.13.3.565"},{"key":"R24","unstructured":"Liu T, Yan H, Kuismanen S, et al: The Role of hPMS1 and hPMS2 in predisposing to colorectal cancer. Cancer Res 61:7798,2001-7802,"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.1.105"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1038\/ng1294-405"},{"key":"R27","unstructured":"Thibodeau SN, French AJ, Roche PC, et al: Altered expression of hMSH2 and hMLH1 in tumours with microsatellite instability and genetic alterations in mismatch repair genes. Cancer Res 56:4836,1996-4840,"},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199910000-00010"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1054\/bjoc.1999.1014"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.54.6.484"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021151227983"},{"key":"R32","unstructured":"M\u00f8ller P: Genetic cancer: A challenge and a possible strategy. J Cancer Care 2:94,1993-99,"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-0956-3"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1038\/3795"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023362205205"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199808203390804"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.5.318"},{"key":"R38","unstructured":"Schweizer P, Moiso AL, Kuismanen SA: Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas in hereditary nonpolyposis colorectal cancer. Cancer Res 61:2813,2001-2815,"},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.11.6616"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8568"},{"key":"R41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001140200"},{"key":"R42","unstructured":"Thibodeau SN, French AJ, Cunningham JM, et al: Microsatellite instability in colorectal cancer: Different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 58:1713,1998-1718,"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201749"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65048-1"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.11206"},{"key":"R46","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.3.382"},{"key":"R47","doi-asserted-by":"publisher","DOI":"10.1136\/gut.50.3.291"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013840907881"},{"key":"R49","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.15.8698"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2005.05.180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:07:11Z","timestamp":1653512831000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2005.05.180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,7,20]]},"references-count":49,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2005,7,20]]}},"alternative-id":["10.1200\/JCO.2005.05.180"],"URL":"https:\/\/doi.org\/10.1200\/jco.2005.05.180","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,7,20]]}}}