p53 protein expression patterns associated with TP53 mutations in breast carcinoma
Purpose The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 m...
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| Veröffentlicht in: | Breast cancer research and treatment 2024-08, Vol.207 (1), p.213-222 |
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| creator | Anderson, Sarah A. Bartow, Brooke B. Harada, Shuko Siegal, Gene P. Wei, Shi Dal Zotto, Valeria L. Huang, Xiao |
| description | Purpose
The importance of a
TP53
mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with
TP53
mutations in breast cancers from 64 patients.
Methods
TP53
mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
Results
Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A
TP53
mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a
TP53
mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (
p
|
| doi_str_mv | 10.1007/s10549-024-07357-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11230957</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3076846131</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-40ba025137a01869a09f0be74c4381e607947566ce1692395c153db15a24a8743</originalsourceid><addsrcrecordid>eNp9kctuFDEQRS0EIsPAD7BALbFh01DlZ3uFUAQBKRIIhbXl9ngSR9N2Y7sD5OvjYUJ4LFiUalHn3nL5EvIU4SUCqFcFQXDdA-U9KCZUf32PrFAo1iuK6j5ZAUrVywHkEXlUyiUAaAX6ITligwagSFfk8yxYN-dUfYid_z5nX0pIsZttrT7H0tlSkgu2-k33LdSL7uxTE0xLtbVhpWuqMXtbaudsdiGmyT4mD7Z2V_yT274mX969PTt-359-PPlw_Oa0d0zI2nMYLVCBTFnAQWoLegujV9xxNqCXoDRXQkrnUWrKtHAo2GZEYSm3g-JsTV4ffOdlnPzG-Viz3Zk5h8nmHybZYP6exHBhztOVQaQMdPunNXlx65DT18WXaqZQnN_tbPRpKYaBgoG22i97_g96mZYc2317Sg5cIsNG0QPlciol--3daxDMPjNzyMy0zMzPzMx1Ez378447ya-QGsAOQGmjeO7z793_sb0BBByhqQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3076846131</pqid></control><display><type>article</type><title>p53 protein expression patterns associated with TP53 mutations in breast carcinoma</title><source>MEDLINE</source><source>SpringerLink (Online service)</source><creator>Anderson, Sarah A. ; Bartow, Brooke B. ; Harada, Shuko ; Siegal, Gene P. ; Wei, Shi ; Dal Zotto, Valeria L. ; Huang, Xiao</creator><creatorcontrib>Anderson, Sarah A. ; Bartow, Brooke B. ; Harada, Shuko ; Siegal, Gene P. ; Wei, Shi ; Dal Zotto, Valeria L. ; Huang, Xiao</creatorcontrib><description>Purpose
The importance of a
TP53
mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with
TP53
mutations in breast cancers from 64 patients.
Methods
TP53
mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
Results
Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A
TP53
mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a
TP53
mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (
p
< 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense
TP53
mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (
p
< 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (
p
< 0.05).
Conclusion
These findings suggest that p53 IHC can be a potential surrogate for
TP53
mutations in BC. Different p53 expression patterns may correlate with specific
TP53
genetic mutations in BC.</description><identifier>ISSN: 0167-6806</identifier><identifier>ISSN: 1573-7217</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-024-07357-z</identifier><identifier>PMID: 38900212</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Breast cancer ; Breast carcinoma ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Female ; Frameshift mutation ; High-Throughput Nucleotide Sequencing ; Humans ; Immunohistochemistry ; Medicine ; Medicine & Public Health ; Middle Aged ; Missense mutation ; Mutation ; Next-generation sequencing ; Nonsense mutation ; Oncology ; p53 Protein ; Phenotypes ; Point mutation ; Protein expression ; Proteins ; Tumor Suppressor Protein p53 - genetics ; Tumor Suppressor Protein p53 - metabolism ; Tumors</subject><ispartof>Breast cancer research and treatment, 2024-08, Vol.207 (1), p.213-222</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-40ba025137a01869a09f0be74c4381e607947566ce1692395c153db15a24a8743</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10549-024-07357-z$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-024-07357-z$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,27924,27925,41488,42557,51319</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38900212$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anderson, Sarah A.</creatorcontrib><creatorcontrib>Bartow, Brooke B.</creatorcontrib><creatorcontrib>Harada, Shuko</creatorcontrib><creatorcontrib>Siegal, Gene P.</creatorcontrib><creatorcontrib>Wei, Shi</creatorcontrib><creatorcontrib>Dal Zotto, Valeria L.</creatorcontrib><creatorcontrib>Huang, Xiao</creatorcontrib><title>p53 protein expression patterns associated with TP53 mutations in breast carcinoma</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Purpose
The importance of a
TP53
mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with
TP53
mutations in breast cancers from 64 patients.
Methods
TP53
mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
Results
Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A
TP53
mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a
TP53
mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (
p
< 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense
TP53
mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (
p
< 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (
p
< 0.05).
Conclusion
These findings suggest that p53 IHC can be a potential surrogate for
TP53
mutations in BC. Different p53 expression patterns may correlate with specific
TP53
genetic mutations in BC.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Breast cancer</subject><subject>Breast carcinoma</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Female</subject><subject>Frameshift mutation</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Missense mutation</subject><subject>Mutation</subject><subject>Next-generation sequencing</subject><subject>Nonsense mutation</subject><subject>Oncology</subject><subject>p53 Protein</subject><subject>Phenotypes</subject><subject>Point mutation</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><subject>Tumors</subject><issn>0167-6806</issn><issn>1573-7217</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kctuFDEQRS0EIsPAD7BALbFh01DlZ3uFUAQBKRIIhbXl9ngSR9N2Y7sD5OvjYUJ4LFiUalHn3nL5EvIU4SUCqFcFQXDdA-U9KCZUf32PrFAo1iuK6j5ZAUrVywHkEXlUyiUAaAX6ITligwagSFfk8yxYN-dUfYid_z5nX0pIsZttrT7H0tlSkgu2-k33LdSL7uxTE0xLtbVhpWuqMXtbaudsdiGmyT4mD7Z2V_yT274mX969PTt-359-PPlw_Oa0d0zI2nMYLVCBTFnAQWoLegujV9xxNqCXoDRXQkrnUWrKtHAo2GZEYSm3g-JsTV4ffOdlnPzG-Viz3Zk5h8nmHybZYP6exHBhztOVQaQMdPunNXlx65DT18WXaqZQnN_tbPRpKYaBgoG22i97_g96mZYc2317Sg5cIsNG0QPlciol--3daxDMPjNzyMy0zMzPzMx1Ez378447ya-QGsAOQGmjeO7z793_sb0BBByhqQ</recordid><startdate>20240801</startdate><enddate>20240801</enddate><creator>Anderson, Sarah A.</creator><creator>Bartow, Brooke B.</creator><creator>Harada, Shuko</creator><creator>Siegal, Gene P.</creator><creator>Wei, Shi</creator><creator>Dal Zotto, Valeria L.</creator><creator>Huang, Xiao</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>C6C</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>7TO</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20240801</creationdate><title>p53 protein expression patterns associated with TP53 mutations in breast carcinoma</title><author>Anderson, Sarah A. ; Bartow, Brooke B. ; Harada, Shuko ; Siegal, Gene P. ; Wei, Shi ; Dal Zotto, Valeria L. ; Huang, Xiao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-40ba025137a01869a09f0be74c4381e607947566ce1692395c153db15a24a8743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Breast cancer</topic><topic>Breast carcinoma</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Female</topic><topic>Frameshift mutation</topic><topic>High-Throughput Nucleotide Sequencing</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Missense mutation</topic><topic>Mutation</topic><topic>Next-generation sequencing</topic><topic>Nonsense mutation</topic><topic>Oncology</topic><topic>p53 Protein</topic><topic>Phenotypes</topic><topic>Point mutation</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anderson, Sarah A.</creatorcontrib><creatorcontrib>Bartow, Brooke B.</creatorcontrib><creatorcontrib>Harada, Shuko</creatorcontrib><creatorcontrib>Siegal, Gene P.</creatorcontrib><creatorcontrib>Wei, Shi</creatorcontrib><creatorcontrib>Dal Zotto, Valeria L.</creatorcontrib><creatorcontrib>Huang, Xiao</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anderson, Sarah A.</au><au>Bartow, Brooke B.</au><au>Harada, Shuko</au><au>Siegal, Gene P.</au><au>Wei, Shi</au><au>Dal Zotto, Valeria L.</au><au>Huang, Xiao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>p53 protein expression patterns associated with TP53 mutations in breast carcinoma</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2024-08-01</date><risdate>2024</risdate><volume>207</volume><issue>1</issue><spage>213</spage><epage>222</epage><pages>213-222</pages><issn>0167-6806</issn><issn>1573-7217</issn><eissn>1573-7217</eissn><abstract>Purpose
The importance of a
TP53
mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with
TP53
mutations in breast cancers from 64 patients.
Methods
TP53
mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC).
Results
Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A
TP53
mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a
TP53
mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (
p
< 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense
TP53
mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (
p
< 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (
p
< 0.05).
Conclusion
These findings suggest that p53 IHC can be a potential surrogate for
TP53
mutations in BC. Different p53 expression patterns may correlate with specific
TP53
genetic mutations in BC.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38900212</pmid><doi>10.1007/s10549-024-07357-z</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Breast cancer Breast carcinoma Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Female Frameshift mutation High-Throughput Nucleotide Sequencing Humans Immunohistochemistry Medicine Medicine & Public Health Middle Aged Missense mutation Mutation Next-generation sequencing Nonsense mutation Oncology p53 Protein Phenotypes Point mutation Protein expression Proteins Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Tumors |
| title | p53 protein expression patterns associated with TP53 mutations in breast carcinoma |
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