Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma
Defective DNA mismatch repair in neoplasia is manifested by extra, aberrant bands within multiple microsatellite markers. The replication error (RER) phenotype is present in most colorectal and endometrial carcinomas in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. In addi...
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| Veröffentlicht in: | The American journal of pathology 1996-05, Vol.148 (5), p.1671-1678 |
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| creator | Caduff, RF Johnston, CM Svoboda-Newman, SM Poy, EL Merajver, SD Frank, TS |
| description | Defective DNA mismatch repair in neoplasia is manifested by extra, aberrant bands within multiple microsatellite markers. The replication error (RER) phenotype is present in most colorectal and endometrial carcinomas in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. In addition, a minority of sporadic colorectal and endometrial carcinomas are RER positive. RER in sporadic colorectal carcinomas has been associated with improved prognosis, but its clinical significance in sporadic endometrial cancer has not been characterized. We analyzed DNA extracted from 109 formalin-fixed sporadic endometrial carcinomas for microsatellite instability. The RER-positive phenotype was demonstrated by microsatellite instability in more than one of the eight dinucleotide markers tested. RER was correlated with pathological and clinical parameters as well as with immunohistochemical staining for the p53 gene product and alterations in codon 12 of Ki-ras. Nine percent of the endometrial carcinomas were RER positive, and RER was significantly associated with high grade and adverse outcome. We found no significant correlation of RER with histological subtype, stage, depth of invasion, mutations in the 12th codon of Ki-ras, or p53 immunoreactivity. We conclude that the RER phenotype is present in a minority of sporadic endometrial carcinomas and is associated with high grade and poor prognosis. |
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The replication error (RER) phenotype is present in most colorectal and endometrial carcinomas in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. In addition, a minority of sporadic colorectal and endometrial carcinomas are RER positive. RER in sporadic colorectal carcinomas has been associated with improved prognosis, but its clinical significance in sporadic endometrial cancer has not been characterized. We analyzed DNA extracted from 109 formalin-fixed sporadic endometrial carcinomas for microsatellite instability. The RER-positive phenotype was demonstrated by microsatellite instability in more than one of the eight dinucleotide markers tested. RER was correlated with pathological and clinical parameters as well as with immunohistochemical staining for the p53 gene product and alterations in codon 12 of Ki-ras. Nine percent of the endometrial carcinomas were RER positive, and RER was significantly associated with high grade and adverse outcome. We found no significant correlation of RER with histological subtype, stage, depth of invasion, mutations in the 12th codon of Ki-ras, or p53 immunoreactivity. We conclude that the RER phenotype is present in a minority of sporadic endometrial carcinomas and is associated with high grade and poor prognosis.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>PMID: 8623934</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: ASIP</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Base Sequence ; Biological and medical sciences ; DNA Primers - chemistry ; DNA, Neoplasm - genetics ; Endometrial Neoplasms - chemistry ; Endometrial Neoplasms - genetics ; Endometrial Neoplasms - pathology ; Female ; Female genital diseases ; Gene Expression Regulation, Neoplastic ; Genes, p53 - genetics ; Genes, ras - genetics ; Genotype ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Medical sciences ; Microsatellite Repeats - genetics ; Middle Aged ; Molecular Sequence Data ; Mutation ; Phenotype ; Polymerase Chain Reaction ; Prognosis ; ras Proteins - analysis ; ras Proteins - genetics ; Tumor Suppressor Protein p53 - analysis ; Tumor Suppressor Protein p53 - genetics ; Tumors</subject><ispartof>The American journal of pathology, 1996-05, Vol.148 (5), p.1671-1678</ispartof><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1861548/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1861548/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3077231$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8623934$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caduff, RF</creatorcontrib><creatorcontrib>Johnston, CM</creatorcontrib><creatorcontrib>Svoboda-Newman, SM</creatorcontrib><creatorcontrib>Poy, EL</creatorcontrib><creatorcontrib>Merajver, SD</creatorcontrib><creatorcontrib>Frank, TS</creatorcontrib><title>Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Defective DNA mismatch repair in neoplasia is manifested by extra, aberrant bands within multiple microsatellite markers. The replication error (RER) phenotype is present in most colorectal and endometrial carcinomas in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. In addition, a minority of sporadic colorectal and endometrial carcinomas are RER positive. RER in sporadic colorectal carcinomas has been associated with improved prognosis, but its clinical significance in sporadic endometrial cancer has not been characterized. We analyzed DNA extracted from 109 formalin-fixed sporadic endometrial carcinomas for microsatellite instability. The RER-positive phenotype was demonstrated by microsatellite instability in more than one of the eight dinucleotide markers tested. RER was correlated with pathological and clinical parameters as well as with immunohistochemical staining for the p53 gene product and alterations in codon 12 of Ki-ras. Nine percent of the endometrial carcinomas were RER positive, and RER was significantly associated with high grade and adverse outcome. We found no significant correlation of RER with histological subtype, stage, depth of invasion, mutations in the 12th codon of Ki-ras, or p53 immunoreactivity. We conclude that the RER phenotype is present in a minority of sporadic endometrial carcinomas and is associated with high grade and poor prognosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>DNA Primers - chemistry</subject><subject>DNA, Neoplasm - genetics</subject><subject>Endometrial Neoplasms - chemistry</subject><subject>Endometrial Neoplasms - genetics</subject><subject>Endometrial Neoplasms - pathology</subject><subject>Female</subject><subject>Female genital diseases</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genes, p53 - genetics</subject><subject>Genes, ras - genetics</subject><subject>Genotype</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Microsatellite Repeats - genetics</subject><subject>Middle Aged</subject><subject>Molecular Sequence Data</subject><subject>Mutation</subject><subject>Phenotype</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>ras Proteins - analysis</subject><subject>ras Proteins - genetics</subject><subject>Tumor Suppressor Protein p53 - analysis</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumors</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkEtL7TAUhYsoenz8BKGDi44KebVNJ4Icrg8QnOg47Cbp6ZY0qUnPvfjvjXoQHe21sxbfJmuvWNGa1RWjHd0vVoQQVnVCkKPiOKWXvDZcksPiUDaMd1ysimHt0KMGV4I35QzLGFzYfD4k3HgcsvTalmEoJ9QxJFisc7jYEn1aoMes37Iu0xwiGNSl9SZMdomYERqiRh8mOC0OBnDJnu3mSfF88_dpfVc9PN7er68fqpEztlRN22ugjen6lnIpAHhrRKvrvqkFF9RyMKYnOUIboL0wA5GdYb3kjA-Dzv5JcfXFnbf9ZI22fong1BxxgvimAqD67Xgc1Sb8U1Q2tBYyAy52gBhetzYtasKk85fB27BNqpWEcUk_guc_L32f2DWb_T87H1Juc4i5RkzfMU7alnGaY5dfsRE343-MVqUJnMtQquBlpkKqWtEm1_EOZfuTtw</recordid><startdate>19960501</startdate><enddate>19960501</enddate><creator>Caduff, RF</creator><creator>Johnston, CM</creator><creator>Svoboda-Newman, SM</creator><creator>Poy, EL</creator><creator>Merajver, SD</creator><creator>Frank, TS</creator><general>ASIP</general><general>American Society for Investigative Pathology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19960501</creationdate><title>Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma</title><author>Caduff, RF ; Johnston, CM ; Svoboda-Newman, SM ; Poy, EL ; Merajver, SD ; Frank, TS</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h322t-67bca16d9b71384aa37d47c5b654341e3addb0ca116a1b4df089d2b8323ffc1e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Base Sequence</topic><topic>Biological and medical sciences</topic><topic>DNA Primers - chemistry</topic><topic>DNA, Neoplasm - genetics</topic><topic>Endometrial Neoplasms - chemistry</topic><topic>Endometrial Neoplasms - genetics</topic><topic>Endometrial Neoplasms - pathology</topic><topic>Female</topic><topic>Female genital diseases</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes, p53 - genetics</topic><topic>Genes, ras - genetics</topic><topic>Genotype</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Microsatellite Repeats - genetics</topic><topic>Middle Aged</topic><topic>Molecular Sequence Data</topic><topic>Mutation</topic><topic>Phenotype</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>ras Proteins - analysis</topic><topic>ras Proteins - genetics</topic><topic>Tumor Suppressor Protein p53 - analysis</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caduff, RF</creatorcontrib><creatorcontrib>Johnston, CM</creatorcontrib><creatorcontrib>Svoboda-Newman, SM</creatorcontrib><creatorcontrib>Poy, EL</creatorcontrib><creatorcontrib>Merajver, SD</creatorcontrib><creatorcontrib>Frank, TS</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caduff, RF</au><au>Johnston, CM</au><au>Svoboda-Newman, SM</au><au>Poy, EL</au><au>Merajver, SD</au><au>Frank, TS</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>1996-05-01</date><risdate>1996</risdate><volume>148</volume><issue>5</issue><spage>1671</spage><epage>1678</epage><pages>1671-1678</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>Defective DNA mismatch repair in neoplasia is manifested by extra, aberrant bands within multiple microsatellite markers. The replication error (RER) phenotype is present in most colorectal and endometrial carcinomas in patients with the hereditary nonpolyposis colorectal carcinoma syndrome. In addition, a minority of sporadic colorectal and endometrial carcinomas are RER positive. RER in sporadic colorectal carcinomas has been associated with improved prognosis, but its clinical significance in sporadic endometrial cancer has not been characterized. We analyzed DNA extracted from 109 formalin-fixed sporadic endometrial carcinomas for microsatellite instability. The RER-positive phenotype was demonstrated by microsatellite instability in more than one of the eight dinucleotide markers tested. RER was correlated with pathological and clinical parameters as well as with immunohistochemical staining for the p53 gene product and alterations in codon 12 of Ki-ras. Nine percent of the endometrial carcinomas were RER positive, and RER was significantly associated with high grade and adverse outcome. We found no significant correlation of RER with histological subtype, stage, depth of invasion, mutations in the 12th codon of Ki-ras, or p53 immunoreactivity. We conclude that the RER phenotype is present in a minority of sporadic endometrial carcinomas and is associated with high grade and poor prognosis.</abstract><cop>Bethesda, MD</cop><pub>ASIP</pub><pmid>8623934</pmid><tpages>8</tpages></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Base Sequence Biological and medical sciences DNA Primers - chemistry DNA, Neoplasm - genetics Endometrial Neoplasms - chemistry Endometrial Neoplasms - genetics Endometrial Neoplasms - pathology Female Female genital diseases Gene Expression Regulation, Neoplastic Genes, p53 - genetics Genes, ras - genetics Genotype Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Medical sciences Microsatellite Repeats - genetics Middle Aged Molecular Sequence Data Mutation Phenotype Polymerase Chain Reaction Prognosis ras Proteins - analysis ras Proteins - genetics Tumor Suppressor Protein p53 - analysis Tumor Suppressor Protein p53 - genetics Tumors |
| title | Clinical and pathological significance of microsatellite instability in sporadic endometrial carcinoma |
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