{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T06:08:12Z","timestamp":1764655692804,"version":"build-2065373602"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2009,4,17]],"date-time":"2009-04-17T00:00:00Z","timestamp":1239926400000},"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":[[2009,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Human leukocyte antigen (HLA) class I expression defects frequently occur in colorectal cancers bearing mismatch repair (MMR) deficiencies and are interpreted as immune evasion mechanisms to avoid cancer cell recognition and elimination by the immune system. MMR\u2010deficient tumours are thought to be more prone to lose HLA class I expression, due to their frequent generation of aberrant peptides which can stimulate a cytotoxic T\u2010cell\u2010mediated response. MUTYH\u2010associated polyposis (MAP) is a colorectal cancer syndrome caused by defects in the MUTYH DNA repair enzyme. Impairment of MUTYH activity could lead to a surplus of mutated peptides which would be presented to cytotoxic T\u2010cells through the HLA class I molecules. We have studied the frequency of HLA class I expression defects in MAP carcinomas and have compared it to those observed in MMR\u2010deficient and \u2010proficient colorectal tumours. Immunohistochemical detection of the expression of HLA class I, \u03b22\u2010microglobulin (\u03b22m), and antigen\u2010processing machinery molecules was performed in 37 primary MAP carcinomas and nine metastases resected from 29 MAP patients. Furthermore, we sequenced the \u03b2<jats:italic>2m<\/jats:italic>, <jats:italic>TAP1<\/jats:italic>, and <jats:italic>TAP2<\/jats:italic> genes. Defects in HLA class I expression were detected in 65% of primary MAP carcinomas, affecting 72% of patients. HLA class I expression abnormalities were often concomitant with \u03b22m expression loss and mutations in the \u03b2<jats:italic>2m<\/jats:italic> gene. Loss of HLA class I expression is thus a frequent event in MAP carcinomas, similarly to MMR\u2010deficient colorectal tumours. The extensive mutagenic background of these tumours most likely triggers a strong selective pressure, exerted by the immune system on the tumour, which favours the outgrowth of tumour cell clones with an immune evasive phenotype. Our data provide additional evidence for a link between DNA repair deficiencies and altered HLA class I phenotypes in colorectal cancer. Copyright \u00a9 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.2569","type":"journal-article","created":{"date-parts":[[2009,4,19]],"date-time":"2009-04-19T11:07:12Z","timestamp":1240139232000},"page":"69-76","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["MUTYH\u2010associated polyposis carcinomas frequently lose HLA class I expression\u2014a common event amongst DNA\u2010repair\u2010deficient colorectal cancers"],"prefix":"10.1002","volume":"219","author":[{"given":"Noel FCC","family":"de Miranda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maartje","family":"Nielsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjo","family":"van Puijenbroek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans F","family":"Vasen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik J","family":"Hes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"van Wezel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Morreau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2009,5,21]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1672"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.24.021605.090733"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.1999.0195"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-004-0517-9"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-006-0183-1"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.19.1669"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-004-0692-z"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)70795-1"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22691"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-2750"},{"key":"e_1_2_7_12_2","first-page":"1721","article-title":"Characterization of human lymphocyte antigen class I antigen\u2010processing machinery defects in renal cell carcinoma lesions with special emphasis on transporter\u2010associated with antigen\u2010processing down\u2010regulation","volume":"9","author":"Seliger B","year":"2003","journal-title":"Clin Cancer Res"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-7-33"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5462-z"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-6-233"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0044"},{"key":"e_1_2_7_17_2","first-page":"3455","article-title":"Hypermethylation of the hMLH1 promoter in colon cancer with microsatellite instability","volume":"58","author":"Cunningham JM","year":"1998","journal-title":"Cancer Res"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1278"},{"key":"e_1_2_7_19_2","first-page":"133","article-title":"The effect of mismatch repair deficiency on tumourigenesis; microsatellite instability affecting genes containing short repeated sequences","volume":"16","author":"Johannsdottir JT","year":"2000","journal-title":"Int J Oncol"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.1298"},{"key":"e_1_2_7_21_2","first-page":"14","article-title":"Immunogenic peptides generated by frameshift mutations in DNA mismatch repair\u2010deficient cancer cells","volume":"4","author":"Schwitalle Y","year":"2004","journal-title":"Cancer Immunity"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng828"},{"key":"e_1_2_7_23_2","first-page":"S15","article-title":"An autosomal recessive multiple colorectal adenoma and carcinoma syndrome caused by inherited mutations in MYH","volume":"39","author":"Sampson J","year":"2002","journal-title":"J Med Genet"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(04)01595-5"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025283"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715760410001688348"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.24.4912"},{"key":"e_1_2_7_28_2","first-page":"7595","article-title":"Carcinogenesis in MYH\u2010associated polyposis follows a distinct genetic pathway","volume":"63","author":"Lipton L","year":"2003","journal-title":"Cancer Res"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6601747"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.033217"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-1705"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1764"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1934"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.137.7.2299"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(98)00026-1"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.4.1918"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2003.00114.x"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2005.00462.x"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2005.02.006"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1998.tb02274.x"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.38.1.85"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6349(08)71609-4"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.1765"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.4472"},{"key":"e_1_2_7_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65436-3"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00386-9"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.01.015"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2008.04.040"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpath.2569","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.2569","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T10:16:33Z","timestamp":1761041793000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.2569"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,5,21]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2009,9]]}},"alternative-id":["10.1002\/path.2569"],"URL":"https:\/\/doi.org\/10.1002\/path.2569","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"type":"print","value":"0022-3417"},{"type":"electronic","value":"1096-9896"}],"subject":[],"published":{"date-parts":[[2009,5,21]]},"assertion":[{"value":"2008-11-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-04-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}