Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining
Fluorescence in situ hybridization (FISH) and immunohistochemical analysis for assessment of HER-2 status in breast carcinomas are discordant in a significant proportion of cases with equivocal (2+) immunostaining. To evaluate the role of intratumoral heterogeneity and degree of amplification, we pe...
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| Veröffentlicht in: | American journal of clinical pathology 2005-08, Vol.124 (2), p.273-281 |
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| container_title | American journal of clinical pathology |
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| creator | LEWIS, Jason T KETTERLING, Rhett P HAILING, Kevin C REYNOLDS, Carol JENKINS, Robert B VISSCHER, Daniel W |
| description | Fluorescence in situ hybridization (FISH) and immunohistochemical analysis for assessment of HER-2 status in breast carcinomas are discordant in a significant proportion of cases with equivocal (2+) immunostaining. To evaluate the role of intratumoral heterogeneity and degree of amplification, we performed additional HER-2 immunostains and FISH on tumor-bearing blocks from 20 invasive breast carcinomas with immunohistochemical scores of 2+ with gene amplification and in 18 cases without amplification. Of the amplified cases, 11 (55%) had a 3+ immunohistochemical score on at least 1 additional slide, 8 (40%) remained 2+, and 1 (5%) had a slide scored 1+. All cases rescored 3+ showed high-level amplification in original and repeated FISH; cases remaining 2+ had a heterogeneous FISH profile (low-level amplification or a mosaic mixture of high-level amplified and nonamplified cells) in original and repeated FISH. Of nonamplified cases, 13 (72%) had a 1+ score on at least 1 additional slide, 4 (22%) remained 2+, and 1 (6%) had 1 slide scored 3+. In the nonamplified cases, 17 (94%) showed no amplification in repeated FISH. Significant intratumoral heterogeneity and minimal (low-level) HER-2 amplification account for many breast cancers with 2+ HER-2 protein expression. |
| doi_str_mv | 10.1309/J9VXABUGKC4Y07DL |
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To evaluate the role of intratumoral heterogeneity and degree of amplification, we performed additional HER-2 immunostains and FISH on tumor-bearing blocks from 20 invasive breast carcinomas with immunohistochemical scores of 2+ with gene amplification and in 18 cases without amplification. Of the amplified cases, 11 (55%) had a 3+ immunohistochemical score on at least 1 additional slide, 8 (40%) remained 2+, and 1 (5%) had a slide scored 1+. All cases rescored 3+ showed high-level amplification in original and repeated FISH; cases remaining 2+ had a heterogeneous FISH profile (low-level amplification or a mosaic mixture of high-level amplified and nonamplified cells) in original and repeated FISH. Of nonamplified cases, 13 (72%) had a 1+ score on at least 1 additional slide, 4 (22%) remained 2+, and 1 (6%) had 1 slide scored 3+. In the nonamplified cases, 17 (94%) showed no amplification in repeated FISH. Significant intratumoral heterogeneity and minimal (low-level) HER-2 amplification account for many breast cancers with 2+ HER-2 protein expression.</description><identifier>ISSN: 0002-9173</identifier><identifier>EISSN: 1943-7722</identifier><identifier>DOI: 10.1309/J9VXABUGKC4Y07DL</identifier><identifier>PMID: 16040300</identifier><identifier>CODEN: AJCPAI</identifier><language>eng</language><publisher>Chicago, IL: American Society of Clinical Pathologists</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Carcinoma, Ductal, Breast - genetics ; Carcinoma, Ductal, Breast - metabolism ; Carcinoma, Ductal, Breast - pathology ; Carcinoma, Intraductal, Noninfiltrating - genetics ; Carcinoma, Intraductal, Noninfiltrating - metabolism ; Carcinoma, Intraductal, Noninfiltrating - pathology ; Carcinoma, Lobular - genetics ; Carcinoma, Lobular - metabolism ; Carcinoma, Lobular - pathology ; Female ; Gene Amplification ; Gynecology. Andrology. Obstetrics ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Investigative techniques, diagnostic techniques (general aspects) ; Mammary gland diseases ; Medical sciences ; Middle Aged ; Pathology. Cytology. Biochemistry. Spectrometry. 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To evaluate the role of intratumoral heterogeneity and degree of amplification, we performed additional HER-2 immunostains and FISH on tumor-bearing blocks from 20 invasive breast carcinomas with immunohistochemical scores of 2+ with gene amplification and in 18 cases without amplification. Of the amplified cases, 11 (55%) had a 3+ immunohistochemical score on at least 1 additional slide, 8 (40%) remained 2+, and 1 (5%) had a slide scored 1+. All cases rescored 3+ showed high-level amplification in original and repeated FISH; cases remaining 2+ had a heterogeneous FISH profile (low-level amplification or a mosaic mixture of high-level amplified and nonamplified cells) in original and repeated FISH. Of nonamplified cases, 13 (72%) had a 1+ score on at least 1 additional slide, 4 (22%) remained 2+, and 1 (6%) had 1 slide scored 3+. In the nonamplified cases, 17 (94%) showed no amplification in repeated FISH. Significant intratumoral heterogeneity and minimal (low-level) HER-2 amplification account for many breast cancers with 2+ HER-2 protein expression.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Carcinoma, Ductal, Breast - genetics</subject><subject>Carcinoma, Ductal, Breast - metabolism</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Carcinoma, Intraductal, Noninfiltrating - genetics</subject><subject>Carcinoma, Intraductal, Noninfiltrating - metabolism</subject><subject>Carcinoma, Intraductal, Noninfiltrating - pathology</subject><subject>Carcinoma, Lobular - genetics</subject><subject>Carcinoma, Lobular - metabolism</subject><subject>Carcinoma, Lobular - pathology</subject><subject>Female</subject><subject>Gene Amplification</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Mammary gland diseases</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Receptor, ErbB-3 - metabolism</subject><subject>Tumors</subject><issn>0002-9173</issn><issn>1943-7722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkM1rFDEYh4Modq3ePUkuFouMvvnYZHJc137pgiBV9DRkMkkbmUm2ScayB_93U7pg8fS-h-f5HR6EXhJ4Rxio95_U9x-rD9_OPq_5T5AfN4_QgijOGikpfYwWAEAbRSQ7QM9y_gVAaAv8KTogAjgwgAX6swp63GWfcXTYh5J0maeY9IivbbEpXtlgfdlhHQasp-3onTe6-BhwLhXN1cF9sjoXbHQyPsRJZ3zryzW2N7P_HU2dekPfHuPzk68NxX6a5hCr64MPV8_RE6fHbF_s7yG6PD25XJ83my9nF-vVpjFMqNL0kvSUOs7kUhHTM8Vca6zkBrjjy2HogXExqPoKkIOTfStEu-wH0Qugg2OH6Oh-dpvizWxz6SafjR1HHWyccydaEJzKZQXhHjQp5pys67bJTzrtOgLdXfHu_-JVebXfnvvJDv-EfeIKvN4DOtcYLulgfH7AKaGoaNlf-sGL1Q</recordid><startdate>20050801</startdate><enddate>20050801</enddate><creator>LEWIS, Jason T</creator><creator>KETTERLING, Rhett P</creator><creator>HAILING, Kevin C</creator><creator>REYNOLDS, Carol</creator><creator>JENKINS, Robert B</creator><creator>VISSCHER, Daniel W</creator><general>American Society of Clinical Pathologists</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></search><sort><creationdate>20050801</creationdate><title>Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining</title><author>LEWIS, Jason T ; KETTERLING, Rhett P ; HAILING, Kevin C ; REYNOLDS, Carol ; JENKINS, Robert B ; VISSCHER, Daniel W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-b71b22f437591cb393f8ce74c04f45ddb0346d945d607df7b86685bd6b602df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Carcinoma, Ductal, Breast - genetics</topic><topic>Carcinoma, Ductal, Breast - metabolism</topic><topic>Carcinoma, Ductal, Breast - pathology</topic><topic>Carcinoma, Intraductal, Noninfiltrating - genetics</topic><topic>Carcinoma, Intraductal, Noninfiltrating - metabolism</topic><topic>Carcinoma, Intraductal, Noninfiltrating - pathology</topic><topic>Carcinoma, Lobular - genetics</topic><topic>Carcinoma, Lobular - metabolism</topic><topic>Carcinoma, Lobular - pathology</topic><topic>Female</topic><topic>Gene Amplification</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Mammary gland diseases</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Receptor, ErbB-3 - metabolism</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>LEWIS, Jason T</creatorcontrib><creatorcontrib>KETTERLING, Rhett P</creatorcontrib><creatorcontrib>HAILING, Kevin C</creatorcontrib><creatorcontrib>REYNOLDS, Carol</creatorcontrib><creatorcontrib>JENKINS, Robert B</creatorcontrib><creatorcontrib>VISSCHER, Daniel W</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><jtitle>American journal of clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>LEWIS, Jason T</au><au>KETTERLING, Rhett P</au><au>HAILING, Kevin C</au><au>REYNOLDS, Carol</au><au>JENKINS, Robert B</au><au>VISSCHER, Daniel W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining</atitle><jtitle>American journal of clinical pathology</jtitle><addtitle>Am J Clin Pathol</addtitle><date>2005-08-01</date><risdate>2005</risdate><volume>124</volume><issue>2</issue><spage>273</spage><epage>281</epage><pages>273-281</pages><issn>0002-9173</issn><eissn>1943-7722</eissn><coden>AJCPAI</coden><abstract>Fluorescence in situ hybridization (FISH) and immunohistochemical analysis for assessment of HER-2 status in breast carcinomas are discordant in a significant proportion of cases with equivocal (2+) immunostaining. To evaluate the role of intratumoral heterogeneity and degree of amplification, we performed additional HER-2 immunostains and FISH on tumor-bearing blocks from 20 invasive breast carcinomas with immunohistochemical scores of 2+ with gene amplification and in 18 cases without amplification. Of the amplified cases, 11 (55%) had a 3+ immunohistochemical score on at least 1 additional slide, 8 (40%) remained 2+, and 1 (5%) had a slide scored 1+. All cases rescored 3+ showed high-level amplification in original and repeated FISH; cases remaining 2+ had a heterogeneous FISH profile (low-level amplification or a mosaic mixture of high-level amplified and nonamplified cells) in original and repeated FISH. Of nonamplified cases, 13 (72%) had a 1+ score on at least 1 additional slide, 4 (22%) remained 2+, and 1 (6%) had 1 slide scored 3+. In the nonamplified cases, 17 (94%) showed no amplification in repeated FISH. Significant intratumoral heterogeneity and minimal (low-level) HER-2 amplification account for many breast cancers with 2+ HER-2 protein expression.</abstract><cop>Chicago, IL</cop><pub>American Society of Clinical Pathologists</pub><pmid>16040300</pmid><doi>10.1309/J9VXABUGKC4Y07DL</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Biological and medical sciences Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - pathology Carcinoma, Intraductal, Noninfiltrating - genetics Carcinoma, Intraductal, Noninfiltrating - metabolism Carcinoma, Intraductal, Noninfiltrating - pathology Carcinoma, Lobular - genetics Carcinoma, Lobular - metabolism Carcinoma, Lobular - pathology Female Gene Amplification Gynecology. Andrology. Obstetrics Humans Immunohistochemistry In Situ Hybridization, Fluorescence Investigative techniques, diagnostic techniques (general aspects) Mammary gland diseases Medical sciences Middle Aged Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Receptor, ErbB-3 - metabolism Tumors |
| title | Analysis of intratumoral heterogeneity and amplification status in breast carcinomas with equivocal (2+) HER-2 immunostaining |
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