Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences
Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunoh...
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| Veröffentlicht in: | Virchows Archiv : an international journal of pathology 2001-01, Vol.438 (1), p.39-48 |
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| creator | CHIARAVALLI, Anna Maria FURLAN, Daniela FACCO, Carla TIBILETTI, Maria Grazia DIONIGI, Adriana CASATI, Barbara ALBARELLO, Luca RIVA, Cristina CAPELLA, Carlo |
| description | Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours. |
| doi_str_mv | 10.1007/s004280000325 |
| format | Article |
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MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.</description><identifier>ISSN: 0945-6317</identifier><identifier>EISSN: 1432-2307</identifier><identifier>DOI: 10.1007/s004280000325</identifier><identifier>PMID: 11213834</identifier><language>eng</language><publisher>Berlin: Springer</publisher><subject>Adaptor Proteins, Signal Transducing ; Adenocarcinoma - chemistry ; Adenocarcinoma - genetics ; Adenocarcinoma - pathology ; Biological and medical sciences ; Carcinoma - chemistry ; Carcinoma - genetics ; Carcinoma - pathology ; Carrier Proteins ; Colorectal Neoplasms - chemistry ; Colorectal Neoplasms - genetics ; Colorectal Neoplasms - pathology ; Cystadenocarcinoma - chemistry ; Cystadenocarcinoma - genetics ; Cystadenocarcinoma - pathology ; DNA Repair ; DNA, Neoplasm - analysis ; DNA-Binding Proteins ; Endometrial Neoplasms - chemistry ; Endometrial Neoplasms - genetics ; Endometrial Neoplasms - pathology ; Female ; Female genital diseases ; Gastroenterology. Liver. Pancreas. Abdomen ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; Medical sciences ; Microsatellite Repeats ; Mutation ; MutL Protein Homolog 1 ; MutS Homolog 2 Protein ; Neoplasm Proteins - analysis ; Nuclear Proteins ; Ovarian Neoplasms - chemistry ; Ovarian Neoplasms - genetics ; Ovarian Neoplasms - pathology ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins - analysis ; Stomach Neoplasms - chemistry ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach. Duodenum. Small intestine. Colon. Rectum. 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MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Adenocarcinoma - chemistry</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - pathology</subject><subject>Biological and medical sciences</subject><subject>Carcinoma - chemistry</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - pathology</subject><subject>Carrier Proteins</subject><subject>Colorectal Neoplasms - chemistry</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Cystadenocarcinoma - chemistry</subject><subject>Cystadenocarcinoma - genetics</subject><subject>Cystadenocarcinoma - pathology</subject><subject>DNA Repair</subject><subject>DNA, Neoplasm - analysis</subject><subject>DNA-Binding Proteins</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>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medical sciences</subject><subject>Microsatellite Repeats</subject><subject>Mutation</subject><subject>MutL Protein Homolog 1</subject><subject>MutS Homolog 2 Protein</subject><subject>Neoplasm Proteins - analysis</subject><subject>Nuclear Proteins</subject><subject>Ovarian Neoplasms - chemistry</subject><subject>Ovarian Neoplasms - genetics</subject><subject>Ovarian Neoplasms - pathology</subject><subject>Polymorphism, Single-Stranded Conformational</subject><subject>Proto-Oncogene Proteins - analysis</subject><subject>Stomach Neoplasms - chemistry</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</subject><subject>Tumors</subject><issn>0945-6317</issn><issn>1432-2307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1KAzEUhYMotlaXbiXgtmPzM5POLEXUFlpcqOtyJ5M4kZmkJqnSN_IxTWlRvJscwse55x6ELim5oYRMJ4GQnJUkDWfFERrSnLOMcTI9RkNS5UUmOJ0O0FkI74QwWlJxigaUMspLng_R97zvN9a1JkQnW9UbCR1eQ4zKW-w0bpfPMzZpl4sZxcZiDb3pTELANjisnYfGSCxd57ySEboxfoMQvZFjrGzjepX0gXafkLTFErw01vUQ8JeJbXINEerkGre7DSmBdwGi6tKPwkF9bJSVKpyjEw1dUBeHd4ReH-5f7mbZ4ulxfne7yGS6M2aiLBSvipLyvGR1WQhGFM9B1DSXTdKi5pTJWkENpa4byUVRaC2qghGuecX5CGV7312M4JVerb3pwW9XlKx2ja_-NZ74qz2_3tS9av7oQ8UJuD4AEFK52oOVJvxyKaKopvwHoaGLWg</recordid><startdate>20010101</startdate><enddate>20010101</enddate><creator>CHIARAVALLI, Anna Maria</creator><creator>FURLAN, Daniela</creator><creator>FACCO, Carla</creator><creator>TIBILETTI, Maria Grazia</creator><creator>DIONIGI, Adriana</creator><creator>CASATI, Barbara</creator><creator>ALBARELLO, Luca</creator><creator>RIVA, Cristina</creator><creator>CAPELLA, Carlo</creator><general>Springer</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20010101</creationdate><title>Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences</title><author>CHIARAVALLI, Anna Maria ; FURLAN, Daniela ; FACCO, Carla ; TIBILETTI, Maria Grazia ; DIONIGI, Adriana ; CASATI, Barbara ; ALBARELLO, Luca ; RIVA, Cristina ; CAPELLA, Carlo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c317t-685e395813482b85620e34a6b14cd20e6b312cbeaba8fbdc3655ff695203f3933</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Adenocarcinoma - chemistry</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - pathology</topic><topic>Biological and medical sciences</topic><topic>Carcinoma - chemistry</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - pathology</topic><topic>Carrier Proteins</topic><topic>Colorectal Neoplasms - chemistry</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - pathology</topic><topic>Cystadenocarcinoma - chemistry</topic><topic>Cystadenocarcinoma - genetics</topic><topic>Cystadenocarcinoma - pathology</topic><topic>DNA Repair</topic><topic>DNA, Neoplasm - analysis</topic><topic>DNA-Binding Proteins</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>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medical sciences</topic><topic>Microsatellite Repeats</topic><topic>Mutation</topic><topic>MutL Protein Homolog 1</topic><topic>MutS Homolog 2 Protein</topic><topic>Neoplasm Proteins - analysis</topic><topic>Nuclear Proteins</topic><topic>Ovarian Neoplasms - chemistry</topic><topic>Ovarian Neoplasms - genetics</topic><topic>Ovarian Neoplasms - pathology</topic><topic>Polymorphism, Single-Stranded Conformational</topic><topic>Proto-Oncogene Proteins - analysis</topic><topic>Stomach Neoplasms - chemistry</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach. Duodenum. Small intestine. Colon. Rectum. Anus</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>CHIARAVALLI, Anna Maria</creatorcontrib><creatorcontrib>FURLAN, Daniela</creatorcontrib><creatorcontrib>FACCO, Carla</creatorcontrib><creatorcontrib>TIBILETTI, Maria Grazia</creatorcontrib><creatorcontrib>DIONIGI, Adriana</creatorcontrib><creatorcontrib>CASATI, Barbara</creatorcontrib><creatorcontrib>ALBARELLO, Luca</creatorcontrib><creatorcontrib>RIVA, Cristina</creatorcontrib><creatorcontrib>CAPELLA, Carlo</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>CrossRef</collection><jtitle>Virchows Archiv : an international journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>CHIARAVALLI, Anna Maria</au><au>FURLAN, Daniela</au><au>FACCO, Carla</au><au>TIBILETTI, Maria Grazia</au><au>DIONIGI, Adriana</au><au>CASATI, Barbara</au><au>ALBARELLO, Luca</au><au>RIVA, Cristina</au><au>CAPELLA, Carlo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences</atitle><jtitle>Virchows Archiv : an international journal of pathology</jtitle><addtitle>Virchows Arch</addtitle><date>2001-01-01</date><risdate>2001</risdate><volume>438</volume><issue>1</issue><spage>39</spage><epage>48</epage><pages>39-48</pages><issn>0945-6317</issn><eissn>1432-2307</eissn><abstract>Alterations of DNA mismatch repair (MMR) genes are involved in carcinogenesis of sporadic and inherited human cancers characterised by instability of DNA microsatellite sequences (MSI). MSI tumours are usually identified using molecular analysis. In the present investigation, hMLH1 and hMSH2 immunohistochemistry was tested in order to evaluate the utility of this method in predicting MMR deficiency. Colorectal (72), gastric (68), endometrial (44) and ovarian (17) carcinomas were independently evaluated for familial history, histological type of tumour, MSI status and immunohistochemical results. Loss of expression of either hMLH1 or hMSH2 was observed in 51 of 55 (92.8%) MSI tumours, while 145 of 146 microsatellite stable (MSS) tumours expressed both the hMLH1 and hMSH2 gene products. Independently of tumour site, an overall agreement between immunohistochemical and molecular results was observed in 15 hereditary non-polyposis colorectal cancer-related tumours. Among sporadic tumours, only 2 of 60 colorectal and 2 of 66 gastric carcinomas, displaying MSI, expressed both hMLH1 and hMSH2 gene products. All 39 endometrial and 16 ovarian tumours presented a concordant molecular and immunohistochemical profile. These data show that immunohistochemistry is an accurate and rapid method to predict the presence of defective DNA MMR genes and to identify both sporadic and familial MSI tumours.</abstract><cop>Berlin</cop><pub>Springer</pub><pmid>11213834</pmid><doi>10.1007/s004280000325</doi><tpages>10</tpages></addata></record> |
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| identifier | ISSN: 0945-6317 |
| ispartof | Virchows Archiv : an international journal of pathology, 2001-01, Vol.438 (1), p.39-48 |
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| language | eng |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Adaptor Proteins, Signal Transducing Adenocarcinoma - chemistry Adenocarcinoma - genetics Adenocarcinoma - pathology Biological and medical sciences Carcinoma - chemistry Carcinoma - genetics Carcinoma - pathology Carrier Proteins Colorectal Neoplasms - chemistry Colorectal Neoplasms - genetics Colorectal Neoplasms - pathology Cystadenocarcinoma - chemistry Cystadenocarcinoma - genetics Cystadenocarcinoma - pathology DNA Repair DNA, Neoplasm - analysis DNA-Binding Proteins Endometrial Neoplasms - chemistry Endometrial Neoplasms - genetics Endometrial Neoplasms - pathology Female Female genital diseases Gastroenterology. Liver. Pancreas. Abdomen Gynecology. Andrology. Obstetrics Humans Immunohistochemistry Medical sciences Microsatellite Repeats Mutation MutL Protein Homolog 1 MutS Homolog 2 Protein Neoplasm Proteins - analysis Nuclear Proteins Ovarian Neoplasms - chemistry Ovarian Neoplasms - genetics Ovarian Neoplasms - pathology Polymorphism, Single-Stranded Conformational Proto-Oncogene Proteins - analysis Stomach Neoplasms - chemistry Stomach Neoplasms - genetics Stomach Neoplasms - pathology Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumors |
| title | Immunohistochemical pattern of hMSH2/hMLH1 in familial and sporadic colorectal, gastric, endometrial and ovarian carcinomas with instability in microsatellite sequences |
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