CK8/18 expression, the basal phenotype, and family history in identifying BRCA1‐associated breast cancer in the Ontario site of the Breast Cancer Family Registry
BACKGROUND. BRCA1‐associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1‐associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic f...
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| Veröffentlicht in: | Cancer 2011-04, Vol.117 (7), p.1350-1359 |
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| creator | Mulligan, Anna Marie Pinnaduwage, Dushanthi Bane, Anita L. Bull, Shelley B. O'Malley, Frances P. Andrulis, Irene L. |
| description | BACKGROUND.
BRCA1‐associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1‐associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1‐associated tumor profile in a pathologically well‐characterized cohort would be improved.
METHODS.
Fifty‐eight patients with known BRCA1 germline mutations and 221 control (familial non‐BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was ed. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best‐subsets variable‐selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1‐associated tumors from non‐BRCA associated tumors.
RESULTS.
BRCA1‐associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non‐BRCA tumors, whether they were basal‐like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1‐associated cancers.
CONCLUSIONS.
CK8/18 expression was independently associated with BRCA1‐associated breast cancers. Reduced CK8/18 expression in conjunction with the basal‐like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing. Cancer 2011. © 2010 American Cancer Society.
Reduced CK8/18 expression was significantly associated with BRCA1 germline mutations. In conjunction with the basal‐like phenotype and family history, this association may have helped streamline genetic testing. |
| doi_str_mv | 10.1002/cncr.25642 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3116977</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>858283298</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5152-d56b565a1f62dc8866a947c7d25151ae2cf1716baba2a65b8f4cf15f2dc8a58a3</originalsourceid><addsrcrecordid>eNp9kcFu1DAQhi0EokvhwgMgXxASalrbiRPvBamNKCAqKq1A4mZNHHvXKGundhbIjUfgHfpmfRKcZilw4TSamU__7_GP0FNKjikh7EQ5FY4ZLwt2Dy0oWVYZoQW7jxaEEJHxIv98gB7F-CW1FeP5Q3TA0p7TvFig6_q9OKEC6-990DFa747wsNG4gQgd7jfa-WHs9REG12IDW9uNeGPj4MOIrcO21W6wZrRujc9W9Sm9-fETYvTKwqBb3AQNccAKnNJh4ifpSzdAsB5HO2jsze3sbAbrGTyffVZ6nZzC-Bg9MNBF_WRfD9Gn89cf67fZxeWbd_XpRaY45SxrednwkgM1JWuVEGUJy6JSVZtO5RQ0U4ZWtGygAQYlb4Qp0oSbCQYuID9Er2bdftdsdavSaQE62Qe7hTBKD1b-u3F2I9f-q8wpLZdVlQRe7AWCv9rpOMitjUp3HTjtd1EKLpjI2VIk8uVMquBjDNrcuVAip1DlFKq8DTXBz_5-1x36O8UEPN8DEBV0JqRvtPEPly9LWhCSODpz32ynx_9YyvpDvZrNfwFlWb2i</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>858283298</pqid></control><display><type>article</type><title>CK8/18 expression, the basal phenotype, and family history in identifying BRCA1‐associated breast cancer in the Ontario site of the Breast Cancer Family Registry</title><source>Wiley Free Content</source><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Mulligan, Anna Marie ; Pinnaduwage, Dushanthi ; Bane, Anita L. ; Bull, Shelley B. ; O'Malley, Frances P. ; Andrulis, Irene L.</creator><creatorcontrib>Mulligan, Anna Marie ; Pinnaduwage, Dushanthi ; Bane, Anita L. ; Bull, Shelley B. ; O'Malley, Frances P. ; Andrulis, Irene L.</creatorcontrib><description>BACKGROUND.
BRCA1‐associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1‐associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1‐associated tumor profile in a pathologically well‐characterized cohort would be improved.
METHODS.
Fifty‐eight patients with known BRCA1 germline mutations and 221 control (familial non‐BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was ed. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best‐subsets variable‐selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1‐associated tumors from non‐BRCA associated tumors.
RESULTS.
BRCA1‐associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non‐BRCA tumors, whether they were basal‐like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1‐associated cancers.
CONCLUSIONS.
CK8/18 expression was independently associated with BRCA1‐associated breast cancers. Reduced CK8/18 expression in conjunction with the basal‐like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing. Cancer 2011. © 2010 American Cancer Society.
Reduced CK8/18 expression was significantly associated with BRCA1 germline mutations. In conjunction with the basal‐like phenotype and family history, this association may have helped streamline genetic testing.</description><identifier>ISSN: 0008-543X</identifier><identifier>EISSN: 1097-0142</identifier><identifier>DOI: 10.1002/cncr.25642</identifier><identifier>PMID: 21425134</identifier><identifier>CODEN: CANCAR</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>basal subtype ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; BRCA1 ; breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Carcinoma, Basal Cell - metabolism ; CK8/18 ; Family Health ; Female ; Genes, BRCA1 ; Gynecology. Andrology. Obstetrics ; Humans ; Keratin-18 - metabolism ; Keratin-8 - metabolism ; Mammary gland diseases ; Medical sciences ; Ontario ; Phenotype ; Registries ; Tumors</subject><ispartof>Cancer, 2011-04, Vol.117 (7), p.1350-1359</ispartof><rights>Copyright © 2010 American Cancer Society</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010 American Cancer Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5152-d56b565a1f62dc8866a947c7d25151ae2cf1716baba2a65b8f4cf15f2dc8a58a3</citedby><cites>FETCH-LOGICAL-c5152-d56b565a1f62dc8866a947c7d25151ae2cf1716baba2a65b8f4cf15f2dc8a58a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncr.25642$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncr.25642$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23961400$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21425134$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mulligan, Anna Marie</creatorcontrib><creatorcontrib>Pinnaduwage, Dushanthi</creatorcontrib><creatorcontrib>Bane, Anita L.</creatorcontrib><creatorcontrib>Bull, Shelley B.</creatorcontrib><creatorcontrib>O'Malley, Frances P.</creatorcontrib><creatorcontrib>Andrulis, Irene L.</creatorcontrib><title>CK8/18 expression, the basal phenotype, and family history in identifying BRCA1‐associated breast cancer in the Ontario site of the Breast Cancer Family Registry</title><title>Cancer</title><addtitle>Cancer</addtitle><description>BACKGROUND.
BRCA1‐associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1‐associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1‐associated tumor profile in a pathologically well‐characterized cohort would be improved.
METHODS.
Fifty‐eight patients with known BRCA1 germline mutations and 221 control (familial non‐BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was ed. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best‐subsets variable‐selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1‐associated tumors from non‐BRCA associated tumors.
RESULTS.
BRCA1‐associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non‐BRCA tumors, whether they were basal‐like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1‐associated cancers.
CONCLUSIONS.
CK8/18 expression was independently associated with BRCA1‐associated breast cancers. Reduced CK8/18 expression in conjunction with the basal‐like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing. Cancer 2011. © 2010 American Cancer Society.
Reduced CK8/18 expression was significantly associated with BRCA1 germline mutations. In conjunction with the basal‐like phenotype and family history, this association may have helped streamline genetic testing.</description><subject>basal subtype</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>BRCA1</subject><subject>breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Carcinoma, Basal Cell - metabolism</subject><subject>CK8/18</subject><subject>Family Health</subject><subject>Female</subject><subject>Genes, BRCA1</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Keratin-18 - metabolism</subject><subject>Keratin-8 - metabolism</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Ontario</subject><subject>Phenotype</subject><subject>Registries</subject><subject>Tumors</subject><issn>0008-543X</issn><issn>1097-0142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi0EokvhwgMgXxASalrbiRPvBamNKCAqKq1A4mZNHHvXKGundhbIjUfgHfpmfRKcZilw4TSamU__7_GP0FNKjikh7EQ5FY4ZLwt2Dy0oWVYZoQW7jxaEEJHxIv98gB7F-CW1FeP5Q3TA0p7TvFig6_q9OKEC6-990DFa747wsNG4gQgd7jfa-WHs9REG12IDW9uNeGPj4MOIrcO21W6wZrRujc9W9Sm9-fETYvTKwqBb3AQNccAKnNJh4ifpSzdAsB5HO2jsze3sbAbrGTyffVZ6nZzC-Bg9MNBF_WRfD9Gn89cf67fZxeWbd_XpRaY45SxrednwkgM1JWuVEGUJy6JSVZtO5RQ0U4ZWtGygAQYlb4Qp0oSbCQYuID9Er2bdftdsdavSaQE62Qe7hTBKD1b-u3F2I9f-q8wpLZdVlQRe7AWCv9rpOMitjUp3HTjtd1EKLpjI2VIk8uVMquBjDNrcuVAip1DlFKq8DTXBz_5-1x36O8UEPN8DEBV0JqRvtPEPly9LWhCSODpz32ynx_9YyvpDvZrNfwFlWb2i</recordid><startdate>20110401</startdate><enddate>20110401</enddate><creator>Mulligan, Anna Marie</creator><creator>Pinnaduwage, Dushanthi</creator><creator>Bane, Anita L.</creator><creator>Bull, Shelley B.</creator><creator>O'Malley, Frances P.</creator><creator>Andrulis, Irene L.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley-Blackwell</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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110401</creationdate><title>CK8/18 expression, the basal phenotype, and family history in identifying BRCA1‐associated breast cancer in the Ontario site of the Breast Cancer Family Registry</title><author>Mulligan, Anna Marie ; Pinnaduwage, Dushanthi ; Bane, Anita L. ; Bull, Shelley B. ; O'Malley, Frances P. ; Andrulis, Irene L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5152-d56b565a1f62dc8866a947c7d25151ae2cf1716baba2a65b8f4cf15f2dc8a58a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>basal subtype</topic><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - genetics</topic><topic>BRCA1</topic><topic>breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Carcinoma, Basal Cell - metabolism</topic><topic>CK8/18</topic><topic>Family Health</topic><topic>Female</topic><topic>Genes, BRCA1</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Keratin-18 - metabolism</topic><topic>Keratin-8 - metabolism</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Ontario</topic><topic>Phenotype</topic><topic>Registries</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mulligan, Anna Marie</creatorcontrib><creatorcontrib>Pinnaduwage, Dushanthi</creatorcontrib><creatorcontrib>Bane, Anita L.</creatorcontrib><creatorcontrib>Bull, Shelley B.</creatorcontrib><creatorcontrib>O'Malley, Frances P.</creatorcontrib><creatorcontrib>Andrulis, Irene L.</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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mulligan, Anna Marie</au><au>Pinnaduwage, Dushanthi</au><au>Bane, Anita L.</au><au>Bull, Shelley B.</au><au>O'Malley, Frances P.</au><au>Andrulis, Irene L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CK8/18 expression, the basal phenotype, and family history in identifying BRCA1‐associated breast cancer in the Ontario site of the Breast Cancer Family Registry</atitle><jtitle>Cancer</jtitle><addtitle>Cancer</addtitle><date>2011-04-01</date><risdate>2011</risdate><volume>117</volume><issue>7</issue><spage>1350</spage><epage>1359</epage><pages>1350-1359</pages><issn>0008-543X</issn><eissn>1097-0142</eissn><coden>CANCAR</coden><abstract>BACKGROUND.
BRCA1‐associated breast cancer had been shown to be morphologically and genetically distinct from sporadic cancers. The aim of this study was to determine the association of CK8/18 with BRCA1‐associated tumors and if, by using CK8/18 and basal biomarkers in conjunction with morphologic features and family history characteristics, the specificity of the BRCA1‐associated tumor profile in a pathologically well‐characterized cohort would be improved.
METHODS.
Fifty‐eight patients with known BRCA1 germline mutations and 221 control (familial non‐BRCA) patients were selected from the Ontario Familial Breast Cancer Registry. From this database, information on family history and morphologic features was ed. Tissue microarrays were constructed and immunohistochemistry to determine expression of several biomarkers was performed. After a logistic regression fit, a best‐subsets variable‐selection procedure using model performance and predictive ability measures was applied to find a best predictor to distinguish BRCA1‐associated tumors from non‐BRCA associated tumors.
RESULTS.
BRCA1‐associated tumors differed significantly from control tumors in terms of morphology, family history, and biomarker profile. CK8/18 was highly significantly associated with BRCA1 tumors. Consistently, BRCA1 cancers showed low levels of CK8/18 compared to non‐BRCA tumors, whether they were basal‐like or not. A combination of 7 factors, including CK8/18 and family history, best predicted the BRCA1‐associated cancers.
CONCLUSIONS.
CK8/18 expression was independently associated with BRCA1‐associated breast cancers. Reduced CK8/18 expression in conjunction with the basal‐like phenotype and family history may have improved the ability to identify which tumors were likely to be associated with a BRCA1 germline mutation and thereby help streamline genetic testing. Cancer 2011. © 2010 American Cancer Society.
Reduced CK8/18 expression was significantly associated with BRCA1 germline mutations. In conjunction with the basal‐like phenotype and family history, this association may have helped streamline genetic testing.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21425134</pmid><doi>10.1002/cncr.25642</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Free Content; MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | basal subtype Biological and medical sciences Biomarkers, Tumor - genetics BRCA1 breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Carcinoma, Basal Cell - metabolism CK8/18 Family Health Female Genes, BRCA1 Gynecology. Andrology. Obstetrics Humans Keratin-18 - metabolism Keratin-8 - metabolism Mammary gland diseases Medical sciences Ontario Phenotype Registries Tumors |
| title | CK8/18 expression, the basal phenotype, and family history in identifying BRCA1‐associated breast cancer in the Ontario site of the Breast Cancer Family Registry |
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