Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma: IHC Score Algorithm for FISH
Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely availab...
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| Veröffentlicht in: | Journal of thoracic oncology 2011-03, Vol.6 (3), p.459-465 |
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| creator | Yi, Eunhee S. Boland, Jennifer M. Maleszewski, Joseph J. Roden, Anja C. Oliveira, Andre M. Aubry, Marie-Christine Erickson-Johnson, Michele R. Caron, Bolette L. Li, Yan Tang, Hui Stoddard, Shawn Wampfler, Jason Kulig, Kimary Yang, Ping |
| description | Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach.
One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue.
Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH−. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative.
IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach. |
| doi_str_mv | 10.1097/JTO.0b013e318209edb9 |
| format | Article |
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One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue.
Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH−. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative.
IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.</description><identifier>ISSN: 1556-0864</identifier><identifier>EISSN: 1556-1380</identifier><identifier>DOI: 10.1097/JTO.0b013e318209edb9</identifier><identifier>PMID: 21278610</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenocarcinoma ; Adenocarcinoma - diagnosis ; Adenocarcinoma - genetics ; Adenocarcinoma - metabolism ; Adult ; Aged ; Algorithms ; Anaplastic lymphoma kinase ; Carcinoma, Non-Small-Cell Lung - diagnosis ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cohort Studies ; Female ; Fluorescent in situ hybridization ; Follow-Up Studies ; Gene Rearrangement ; Humans ; Immunoenzyme Techniques ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Male ; Middle Aged ; Neoplasm Staging ; Non-small cell lung carcinoma ; Prognosis ; Receptor Protein-Tyrosine Kinases - genetics ; Receptor Protein-Tyrosine Kinases - metabolism ; Sensitivity and Specificity</subject><ispartof>Journal of thoracic oncology, 2011-03, Vol.6 (3), p.459-465</ispartof><rights>2011 International Association for the Study of Lung Cancer</rights><rights>2011International Association for the Study of Lung Cancer</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5188-78ecea2b3aa253a02ebc0a4acb41b9a03fec9e854d18f1c6b30c9628114985b23</citedby><cites>FETCH-LOGICAL-c5188-78ecea2b3aa253a02ebc0a4acb41b9a03fec9e854d18f1c6b30c9628114985b23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21278610$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yi, Eunhee S.</creatorcontrib><creatorcontrib>Boland, Jennifer M.</creatorcontrib><creatorcontrib>Maleszewski, Joseph J.</creatorcontrib><creatorcontrib>Roden, Anja C.</creatorcontrib><creatorcontrib>Oliveira, Andre M.</creatorcontrib><creatorcontrib>Aubry, Marie-Christine</creatorcontrib><creatorcontrib>Erickson-Johnson, Michele R.</creatorcontrib><creatorcontrib>Caron, Bolette L.</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Tang, Hui</creatorcontrib><creatorcontrib>Stoddard, Shawn</creatorcontrib><creatorcontrib>Wampfler, Jason</creatorcontrib><creatorcontrib>Kulig, Kimary</creatorcontrib><creatorcontrib>Yang, Ping</creatorcontrib><title>Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma: IHC Score Algorithm for FISH</title><title>Journal of thoracic oncology</title><addtitle>J Thorac Oncol</addtitle><description>Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach.
One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue.
Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH−. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative.
IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.</description><subject>Adenocarcinoma</subject><subject>Adenocarcinoma - diagnosis</subject><subject>Adenocarcinoma - genetics</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Anaplastic lymphoma kinase</subject><subject>Carcinoma, Non-Small-Cell Lung - diagnosis</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Fluorescent in situ hybridization</subject><subject>Follow-Up Studies</subject><subject>Gene Rearrangement</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Non-small cell lung carcinoma</subject><subject>Prognosis</subject><subject>Receptor Protein-Tyrosine Kinases - genetics</subject><subject>Receptor Protein-Tyrosine Kinases - metabolism</subject><subject>Sensitivity and Specificity</subject><issn>1556-0864</issn><issn>1556-1380</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u1DAUhS0EoqXwBgh5xyrl-icZhwXSKKKdgRGVaFlbjnMzY0jsYidUvD1uZ1qkLrrwz-J83706hLxlcMqgXnz4cnVxCi0wgYIpDjV2bf2MHLOyrAomFDw__EFV8oi8SukngCxBqpfkiDO-UBWDYzI3IUYczOSCp6Gn61VDje_o2fpyRfsQ6XLzlZ6jR_odTYzGb3FEP1Hn6bfgizSaYaAN5msz-y1tTLTOh9F8vDNd2hCRLodtiG7ajXfCW_Nr8qI3Q8I3h_eE_Dj7fNWsis3F-bpZbgpbMqWKhUKLhrfCGF4KAxxbC0Ya20rW1gZEj7ZGVcqOqZ7ZqhVg64orxmStypaLE_J-772O4feMadKjSzZvazyGOWlVskXJeS1yUu6TNoaUIvb6OrrRxL-agb7tW-e-9eO-M_buMGBuR-weoPuC_3tvwjBhTL-G-Qaj3qEZpp0GxqVQtSw4sBwGgCIfUBn7tMcwt_PHZSJZh95i5yLaSXfBPb3YP_oDnzE</recordid><startdate>201103</startdate><enddate>201103</enddate><creator>Yi, Eunhee S.</creator><creator>Boland, Jennifer M.</creator><creator>Maleszewski, Joseph J.</creator><creator>Roden, Anja C.</creator><creator>Oliveira, Andre M.</creator><creator>Aubry, Marie-Christine</creator><creator>Erickson-Johnson, Michele R.</creator><creator>Caron, Bolette L.</creator><creator>Li, Yan</creator><creator>Tang, Hui</creator><creator>Stoddard, Shawn</creator><creator>Wampfler, Jason</creator><creator>Kulig, Kimary</creator><creator>Yang, Ping</creator><general>Elsevier Inc</general><general>International Association for the Study of Lung Cancer</general><scope>6I.</scope><scope>AAFTH</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>201103</creationdate><title>Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma: IHC Score Algorithm for FISH</title><author>Yi, Eunhee S. ; Boland, Jennifer M. ; Maleszewski, Joseph J. ; Roden, Anja C. ; Oliveira, Andre M. ; Aubry, Marie-Christine ; Erickson-Johnson, Michele R. ; Caron, Bolette L. ; Li, Yan ; Tang, Hui ; Stoddard, Shawn ; Wampfler, Jason ; Kulig, Kimary ; Yang, Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5188-78ecea2b3aa253a02ebc0a4acb41b9a03fec9e854d18f1c6b30c9628114985b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adenocarcinoma</topic><topic>Adenocarcinoma - diagnosis</topic><topic>Adenocarcinoma - genetics</topic><topic>Adenocarcinoma - metabolism</topic><topic>Adult</topic><topic>Aged</topic><topic>Algorithms</topic><topic>Anaplastic lymphoma kinase</topic><topic>Carcinoma, Non-Small-Cell Lung - diagnosis</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Cohort Studies</topic><topic>Female</topic><topic>Fluorescent in situ hybridization</topic><topic>Follow-Up Studies</topic><topic>Gene Rearrangement</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Non-small cell lung carcinoma</topic><topic>Prognosis</topic><topic>Receptor Protein-Tyrosine Kinases - genetics</topic><topic>Receptor Protein-Tyrosine Kinases - metabolism</topic><topic>Sensitivity and Specificity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yi, Eunhee S.</creatorcontrib><creatorcontrib>Boland, Jennifer M.</creatorcontrib><creatorcontrib>Maleszewski, Joseph J.</creatorcontrib><creatorcontrib>Roden, Anja C.</creatorcontrib><creatorcontrib>Oliveira, Andre M.</creatorcontrib><creatorcontrib>Aubry, Marie-Christine</creatorcontrib><creatorcontrib>Erickson-Johnson, Michele R.</creatorcontrib><creatorcontrib>Caron, Bolette L.</creatorcontrib><creatorcontrib>Li, Yan</creatorcontrib><creatorcontrib>Tang, Hui</creatorcontrib><creatorcontrib>Stoddard, Shawn</creatorcontrib><creatorcontrib>Wampfler, Jason</creatorcontrib><creatorcontrib>Kulig, Kimary</creatorcontrib><creatorcontrib>Yang, Ping</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</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>Journal of thoracic oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yi, Eunhee S.</au><au>Boland, Jennifer M.</au><au>Maleszewski, Joseph J.</au><au>Roden, Anja C.</au><au>Oliveira, Andre M.</au><au>Aubry, Marie-Christine</au><au>Erickson-Johnson, Michele R.</au><au>Caron, Bolette L.</au><au>Li, Yan</au><au>Tang, Hui</au><au>Stoddard, Shawn</au><au>Wampfler, Jason</au><au>Kulig, Kimary</au><au>Yang, Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma: IHC Score Algorithm for FISH</atitle><jtitle>Journal of thoracic oncology</jtitle><addtitle>J Thorac Oncol</addtitle><date>2011-03</date><risdate>2011</risdate><volume>6</volume><issue>3</issue><spage>459</spage><epage>465</epage><pages>459-465</pages><issn>1556-0864</issn><eissn>1556-1380</eissn><abstract>Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach.
One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue.
Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH−. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative.
IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>21278610</pmid><doi>10.1097/JTO.0b013e318209edb9</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adenocarcinoma Adenocarcinoma - diagnosis Adenocarcinoma - genetics Adenocarcinoma - metabolism Adult Aged Algorithms Anaplastic lymphoma kinase Carcinoma, Non-Small-Cell Lung - diagnosis Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Cohort Studies Female Fluorescent in situ hybridization Follow-Up Studies Gene Rearrangement Humans Immunoenzyme Techniques Immunohistochemistry In Situ Hybridization, Fluorescence Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - metabolism Male Middle Aged Neoplasm Staging Non-small cell lung carcinoma Prognosis Receptor Protein-Tyrosine Kinases - genetics Receptor Protein-Tyrosine Kinases - metabolism Sensitivity and Specificity |
| title | Correlation of IHC and FISH for ALK Gene Rearrangement in Non-small Cell Lung Carcinoma: IHC Score Algorithm for FISH |
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