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Brizape

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Variome_split_0404_dev

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[ "Statistics", "on", "expression", "imbalances", "across", "human", "chromosomes." ]

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[ "Concept", "of", "‘fusion’", "pathways", "to", "crc" ]

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[ "Conclusion" ]

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[ "Sixty-two", "TAs,", "22", "TVAs/VAs,", "15", "SAs", "and", "10", "MPs", "were", "immunostained", "for", "p53.", "Weak", "expression", "of", "nuclear", "p53", "occurred", "frequently", "within", "the", "proliferative", "compartment", "in", "all", "types", "of", "polyps", "and", "was", "ignored.", "Aberrant", "p53", "expression", "was", "observed", "in", "only", "four", "polyps:", "one", "TA,", "one", "MP", "(Figure", "1B)", "and", "two", "SAs", "(Figure", "2).", "Overall,", "only", "1/84", "(1%)", "conventional", "adenomas", "showed", "aberrant", "expression", "of", "p53", "compared", "with", "3/25", "(12%)", "serrated", "polyps", "with", "dysplasia", "(P", "<", "0.04).", "In", "the", "latter,", "aberrant", "p53", "expression", "coincided", "with", "high-grade", "dysplasia", "and", "reduced", "or", "complete", "loss", "of", "expression", "of", "MGMT", "(Figures", "1B", "and", "2).", "The", "TA", "with", "aberrant", "p53", "expression", "had", "normal", "expression", "of", "MGMT." ]

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[ "At", "present,", "a", "number", "of", "publications", "have", "studied", "the", "value", "of", "the", "revised", "Bethesda", "criteria", "and", "the", "relevant", "diagnostic", "procedures", "[13,14].", "However,", "there", "has", "not", "been", "any", "systematic", "report", "on", "germline", "mutations", "of", "MMR", "genes", "in", "the", "Chinese", "population.", "Moreover,", "we", "found", "that", "research", "from", "some", "countries", "have", "results", "that,", "if", "applied", "to", "the", "NCI", "recommendations,", "may", "have", "resulted", "in", "a", "missed", "HNPCC", "family", "or", "low", "pick-up", "rate", "of", "HNPCC.", "In", "a", "study", "by", "Pinol", "et", "al.", "from", "Spain", "[13],", "287", "out", "of", "1222", "patients", "(23.5%)", "complied", "with", "the", "revised", "Bethesda", "standard.", "Ninety-one", "patients", "(7.4%)", "were", "MSI", "carriers,", "but", "only", "11", "patients", "(0.9%)", "had", "germline", "mutations", "of", "MSH2", "or", "MLH1.", "This", "means", "that", "among", "this", "group,", "only", "0.9%", "of", "patients", "could", "be", "diagnosed", "as", "HNPCC.", "In", "a", "study", "by", "Yearsley", "et", "al.", "[14],", "out", "of", "482", "US", "patients", "with", "colorectal", "cancers,", "87", "patients", "(18%)", "were", "MSI", "carriers", "and", "only", "12", "cases", "(2.5%)", "had", "MMR", "gene", "germline", "mutations.", "These", "results", "may", "be", "explained", "by", "different", "case", "selections", "and", "sensitivity", "of", "the", "tests", "used.", "On", "the", "other", "hand,", "in", "their", "study", "of", "HNPCC", "related", "tumors", "in", "young", "patients", "(<50", "years", "old),", "Niessen", "et", "al.", "[15]", "found", "that", "the", "rate", "of", "MSH2,", "MSH6", "and", "MLH1", "germline", "mutations", "in", "MSI", "carriers", "was", "82%.", "In", "our", "146", "patients", "with", "colorectal", "cancers,", "34", "patients", "(23.3%)", "had", "MSI", "colorectal", "cancer.", "This", "is", "comparable", "to", "the", "studies", "by", "Pinol", "et", "al.", "[13]", "and", "Yearsley", "et", "al.", "[16].", "Wong", "et", "al.", "[17]", "showed", "that", "in", "the", "case", "of", "sporadic", "endometrial", "carcinoma,", "MSI", "endometrial", "carcinoma", "accounted", "for", "26%", "of", "patients.", "Our", "results", "showed", "that", "there", "were", "15", "(10.3%)", "CRCs", "with", "MSI-L", "and", "19", "(13.0%)", "CRCs", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs,", "19", "CRCs", "(55.9%)", "were", "hypermethylated", "at", "the", "MLH1", "promoter,", "which", "accounted", "for", "73.7%", "of", "MSI-H", " ", "CRCs", "and", "33.3%", "of", "MSI", "CRCs.", "Anacleto", "et", "al.", "[21]", "reported", "that", "8", "out", "of", "15", "MSI", "CRCs", "had", "MLH1", "promoter", "hypermethylation,", "which", "was", "similar", "to", "our", "results.", "Kim", "et", "al.", "[10]", "found", "that", "in", "MSI-H", "gastric", "cancers,", "the", "MLH1", "hypermethylation", "occurred", "in", "89%", "of", "patients.", "Bettstetter", "et", "al.", "[20]", "showed", "that", "all", "sporadic", "MSI-H", "MSI-H", "MSI", "80", "yrs", ",", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation", ".", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs", "MSI", " ", "CRCs,", "19", "CRCs", "15", "HNPCC", "related", " ", "tumors", "in", "young", "patients", "(<50", "years", "old),", "Niessen", "et", "al.", "[15]", "found", "that", "the", "rate", "of", "MSH2,", "MSH6", "and", "MLH1", "germline", "mutations", "in", "MSI", "carriers", "was", "82%.", "In", "our", "146", "patients", "with", "colorectal", "cancers,", "34", "patients", "(23.3%)", "had", "MSI", "colorectal", "cancer.", "This", "is", "comparable", "to", "the", "studies", "by", "Pinol", "et", "al.", "[13]", "and", "Yearsley", "et", "al.", "[16].", "Wong", "et", "al.", "[17]", "showed", "that", "in", "the", "case", "of", "sporadic", "endometrial", "carcinoma,", "MSI", "endometrial", "carcinoma", "accounted", "for", "26%", "of", "patients.", "Our", "results", "showed", "that", "there", "were", "15", "(10.3%)", "CRCs", "with", "MSI-L", "and", "19", "(13.0%)", "CRCs", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs,", "19", "CRCs", "(55.9%)", "were", "hypermethylated", "at", "the", "MLH1", "promoter", ",", "which", "accounted", "for", "73.7%", "of", "MSI-H", "CRCs", "and", "33.3%", "of", "MSI", "CRCs.", "Anacleto", "et", "al.", "[21]", "reported", "that", "8", "out", "of", "15", "MSI", "CRCs", "had", "MLH1", "promoter", "hypermethylation,", "which", "was", "similar", "to", "our", "results.", "Kim", "et", "al.", "[10]", "found", "that", "in", "MSI-H", "gastric", "cancers,", "the", "MLH1", "hypermethylation", "occurred", "in", "89%", "of", "patients.", "Bettstetter", "et", "al.", "[20]", "showed", "that", "all", "sporadic", "MSI-H", "CRCs", "were", "hypermethylated", "at", "the", "MLH1", "promoter.", "These", "results", "were", "similar", "to", "ours.", "Fourteen", "out", "of", "16", "MLH1", "negatively", "staining", "CRCs", "were", "hypermethylated", "at", "the", "MLH1promoter.", "Mutation", "analysis", "revealed", "that", "8", "patients", "(23.5%)", "had", "MMR", "gene", "germline", "mutations", "out", "of", "34", "MSI", "patients.", "Five", "patients", "had", "MSH2", "mutations", "and", "3", "had", "MSH6", "mutations,", "while", "no", "MLH1", "mutation", "was", "found.", "There", "were", "2", "82%", ".", "In", "our", "146", "patients", "with", "colorectal", "cancers,", "34", "patients", "(23.3%)", "had", "MSI", "colorectal", "cancer.", "This", "is", "comparable", "to", "the", "studies", "by", "Pinol", "et", "al.", "[13]", "and", "Yearsley", "et", "al.", "[16].", "Wong", "et", "al.", "[17]", "showed", "that", "in", "the", "case", "of", "sporadic", "endometrial", "carcinoma,", "MSI", "endometrial", "carcinoma", "accounted", "for", "26%", "of", "patients.", "Our", "results", "showed", "that", "there", "were", "15", "(10.3%)", "CRCs", "with", "MSI-L", "and", "19", "(13.0%)", "CRCs", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", " ", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs,", "19", "CRCs", "(55.9%)", "were", "hypermethylated", "at", "the", "MLH1", "promoter,", "which", "accounted", "for", "73.7%", "of", "MSI-H", "CRCs", "26%", " ", "of", "patients.", "Our", "results", "showed", "that", "there", "were", "15", "(10.3%)", "CRCs", "with", "MSI-L", "and", "19", "(13.0%)", "CRCs", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs,", "19", "CRCs", " ", "(55.9%)", "were", "hypermethylated", "at", "the", "MLH1", "promoter,", "which", "accounted", "for", "73.7%", "of", "MSI-H", "CRCs", "and", "33.3%", "of", "MSI", "CRCs.", "Anacleto", "et", "al.", "[21]", "reported", "that", "8", "out", "of", "15", "MSI", "CRCs", "had", "MLH1", "promoter", "hypermethylation,", "which", "was", "similar", "to", "our", "results.", "Kim", "et", "al.", "[10]", "found", "that", "in", "MSI-H", "gastric", "cancers,", "the", "MLH1", "hypermethylation", "occurred", "in", "89%", "of", "patients.", "Bettstetter", "et", "al.", "[20]", "showed", "that", "all", "sporadic", "MSI-H", "CRCs", "were", "hypermethylated", "at", "the", "MLH1", "promoter.", "These", "results", "were", "similar", "to", "ours.", "Fourteen", "out", "of", "16", "MLH1", "negatively", "staining", "CRCs", "were", "hypermethylated", "at", "the", "MLH1promoter.", "Mutation", "analysis", "revealed", "that", "8", "patients", "(23.5%)", "had", "MMR", "gene", "germline", "mutations", "out", "of", "34", "MSI", "patients.", "Five", "patients", "had", "MSH2", "mutations", "and", "3", "had", "MSH6", "mutations,", "while", "no", "MLH1", "mutation", "was", "found.", "There", "were", "2", "and", "6", "patients", "who", "had", "mutations", "in", "MSH2", "and", "MSH6", "in", "the", "MSI-L", "and", "MSI-H", "groups,", "respectively.", "Yearsley", "et", "al.", "[15],", "in", "their", "study", "of", "87", "patients", "with", "MSI", "colorectal", "cancers", "CRCs", " ", "with", "MSI-L", "and", "19", "(13.0%)", "CRCs", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "colorectal", "cancer", " ", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs", "CRCs", "17%", ",", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "CRCs", " ", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "rectum", "MSI", " ", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs,", "19", "CRCs", "(55.9%)", "were", "hypermethylated", "at", "the", "MLH1", "promoter,", "which", "accounted", "for", "73.7%", "of", "MSI-H", "CRCs", "and", "33.3%", "of", "MSI", "CRCs", "MSS", "older", "carcinoma", " ", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "CRCs", "MSI", "HNPCC", ".", "In", "a", "study", "by", "Yearsley", "et", "al.", "[14],", "out", "of", "482", "US", "patients", "with", "colorectal", "cancers,", "87", "patients", "(18%)", "were", "MSI", "carriers", "and", "only", "12", "cases", "(2.5%)", "had", "MMR", "gene", "germline", "mutations.", "These", "results", "may", "be", "explained", "by", "different", "case", "selections", "and", "sensitivity", "of", "the", "tests", "used.", "On", "the", "other", "hand,", "in", "their", "study", "of", "HNPCC", "related", "tumors", "in", "young", "patients", "(<50", "years", "old),", "Niessen", "et", "al.", "[15]", "found", "that", "the", "rate", "of", "MSH2,", "MSH6", "and", "MLH1", "germline", "mutations", "in", "MSI", "carriers", "was", "82%.", "In", "our", "146", "patients", "with", "colorectal", "cancers,", "34", "patients", "(23.3%)", "had", "MSI", "colorectal", "cancer.", "This", "is", "comparable", "to", "the", "studies", "by", "Pinol", "et", "al.", "[13]", "and", "Yearsley", "et", "al.", "[16].", "Wong", "et", "al.", "[17]", "showed", "that", "in", "the", "case", "of", "sporadic", "endometrial", "carcinoma,", "MSI", "endometrial", "carcinoma", "accounted", "for", "26%", "of", "patients.", "Our", "results", "showed", "that", "there", "were", "15", "(10.3%)", "CRCs", "with", "MSI-L", "and", "19", "(13.0%)", "CRCs", "with", "MSL-H,", "respectively.", "Lamberti", "et", "al.", "[18]", "reported", "that", "MSI-L", "and", "MSI-H", "accounted", "for", "6%", "and", "17%,", "respectively,", "of", "German", "patients.", "These", "results", "are", "similar", "to", "ours.", "Unexpectedly,", "in", "the", "present", "study,", "the", "age", "of", "patients", "with", "MSS", "colorectal", "cancers", " ", "(60", "yrs)", "was", "similar", "to", "the", "age", "of", "patients", "with", "MSI-H", "(61", "yrs).", "In", "contrast,", "the", "average", "age", "of", "patients", "with", "MSI-L", "colorectal", "cancer", "was", "71,", "which", "was", "quite", "different", "from", "the", "reports", "of", "other", "research", "groups", "[13,15,18].", "In", "a", "study", "of", "1263", "patients", "with", "colorectal", "cancers,", "Benatti", "et", "al.", "[19]", "found", "that", "those", "who", "were", "MSI", "carriers", "tended", "to", "have", "mucinous", "and", "right", "colonic", "tumours.", "Noda", "et", "al.", "[20]", "also", "found", "that", "MSI", "carriers", "have", "more", "right", "colonic", "tumors.", "However,", "in", "our", "study,", "tumors", "in", "the", "MSI", "group", "were", "most", "commonly", "located", "at", "the", "rectum,", "and", "mucinous", "carcinoma", "was", "not", "the", "most", "common", "pathological", "type,", "as", "it", "only", "accounted", "for", "29%.", "Interestingly,", "patients", "in", "our", "MSI-L", "group", "were", "older", "than", "the", "MSS", "group.", "The", "reason", "for", "these", "findings", "is", "uncertain.", "Bettstetter", "et", "al.", "[20]", "reported", "that", "the", "average", "age", "of", "MSI", "CRCs", "with", "MLH1", "negative", "staining", "was", "80", "yrs,", "which", "was", "similar", "to", "our", "results.", "Most", "of", "these", "MSI", "CRCs", "were", "caused", "by", "MLH1", "promoter", "hypermethylation.", "In", "our", "group,", "out", "of", "34", "MSI", "CRCs,", "19", "CRCs", "(55.9%)", "were", "hypermethylated", "at", "the", "MLH1", "promoter,", "which", "accounted", "for", "73.7%", "of", "MSI-H", "CRCs", "and", "33.3%", "of", "MSI", "CRCs.", "Anacleto", "et", "al.", "[21]", "reported", "that", "8", "out", "of", "15", "MSI", "CRCs", "had", "MLH1", "promoter", "hypermethylation,", "which", "was", "similar", "to", "our", "results.", "Kim", "et", "al.", "[10]", "found", "that", "in", "MSI-H", "gastric", "cancers,", "the", "MLH1", "hypermethylation", "occurred", "in", "89%", "of", "patients.", "Bettstetter", "et", "al.", "[20]", "showed", "that", "all", "sporadic", "MSI-H", "CRCs", "were", "hypermethylated", "at", "the", "MLH1", "promoter.", "These", "results", "were", "similar", "to", "ours.", "Fourteen", "out", "of", "16", "MLH1", "negatively", "staining", "CRCs", "were", "hypermethylated", "at", "the", "MLH1promoter.", "Mutation", "analysis", "revealed", "that", "8", "patients", "(", "23.5%", "CRCs", "CRCs", "HNPCC", ".", "In", "2004,", "the", "NCI", "recommended", "the", "revised", "Bethesda", "criteria", "as", "a", "HNPCC", "screening", "guideline", "and", "established", "the", "HNPCC", "diagnostic", "procedures.", "These", "guidelines", "stated", "that", "MSI", "should", "firstly", "be", "identified", "in", "colorectal", "tumor", "tissue,", "and", "then", "genetic", "tests", "would", "be", "performed", "to", "confirm", "MMR", "gene", "germline", "mutations", "in", "a", "blood", "sample", "[6]." ]

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[ "Methods" ]

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