Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma
Aims Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surg...
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| Veröffentlicht in: | Histopathology 2023-05, Vol.82 (6), p.860-869 |
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| container_title | Histopathology |
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| creator | Handa, Takafumi Hayashi, Takuo Ura, Ayako Watanabe, Isamu Takamochi, Kazuya Onagi, Hiroko Kishi, Monami Matsumoto, Naohisa Tajima, Ken Kishikawa, Satsuki Saito, Tsuyoshi Takahashi, Kazuhisa Suzuki, Kenji Yao, Takashi |
| description | Aims
Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites.
Methods and results
The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H‐scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1‐dominant (SCLC‐A), NEUROD1‐dominant (SCLC‐N), ASCL1/NEUROD1 double‐negative with POU2F3 expression (SCLC‐P), and negative for all three markers (SCLC‐I). In whole slides, 40 SCLC‐A (52%), 20 SCLC‐N (26%), 15 SCLC‐P (20%), and two SCLC‐I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P |
| doi_str_mv | 10.1111/his.14872 |
| format | Article |
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Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites.
Methods and results
The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H‐scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1‐dominant (SCLC‐A), NEUROD1‐dominant (SCLC‐N), ASCL1/NEUROD1 double‐negative with POU2F3 expression (SCLC‐P), and negative for all three markers (SCLC‐I). In whole slides, 40 SCLC‐A (52%), 20 SCLC‐N (26%), 15 SCLC‐P (20%), and two SCLC‐I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P = 0.0047; NEUROD1, P = 0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens.
Conclusion
The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients.</description><identifier>ISSN: 0309-0167</identifier><identifier>EISSN: 1365-2559</identifier><identifier>DOI: 10.1111/his.14872</identifier><identifier>PMID: 36715573</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>ASCL1 ; ASCL1 protein ; Basic Helix-Loop-Helix Transcription Factors ; Beta2 protein ; Biopsy ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Lung carcinoma ; Lung Neoplasms - genetics ; Lymph nodes ; Lymphatic Metastasis ; Lymphatic system ; Metastases ; Metastasis ; NEUROD1 ; Octamer Transcription Factors - metabolism ; POU2F3 ; small cell carcinoma ; Small cell lung carcinoma ; Small Cell Lung Carcinoma - genetics ; Tumors</subject><ispartof>Histopathology, 2023-05, Vol.82 (6), p.860-869</ispartof><rights>2023 John Wiley & Sons Ltd.</rights><rights>Copyright © 2023 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3532-711b5b11a359758c13604d077dc372ff98d391addb50d4913562f19994b546693</citedby><cites>FETCH-LOGICAL-c3532-711b5b11a359758c13604d077dc372ff98d391addb50d4913562f19994b546693</cites><orcidid>0000-0001-9690-8440 ; 0000-0002-8544-9370</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fhis.14872$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fhis.14872$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36715573$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Handa, Takafumi</creatorcontrib><creatorcontrib>Hayashi, Takuo</creatorcontrib><creatorcontrib>Ura, Ayako</creatorcontrib><creatorcontrib>Watanabe, Isamu</creatorcontrib><creatorcontrib>Takamochi, Kazuya</creatorcontrib><creatorcontrib>Onagi, Hiroko</creatorcontrib><creatorcontrib>Kishi, Monami</creatorcontrib><creatorcontrib>Matsumoto, Naohisa</creatorcontrib><creatorcontrib>Tajima, Ken</creatorcontrib><creatorcontrib>Kishikawa, Satsuki</creatorcontrib><creatorcontrib>Saito, Tsuyoshi</creatorcontrib><creatorcontrib>Takahashi, Kazuhisa</creatorcontrib><creatorcontrib>Suzuki, Kenji</creatorcontrib><creatorcontrib>Yao, Takashi</creatorcontrib><title>Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma</title><title>Histopathology</title><addtitle>Histopathology</addtitle><description>Aims
Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites.
Methods and results
The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H‐scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1‐dominant (SCLC‐A), NEUROD1‐dominant (SCLC‐N), ASCL1/NEUROD1 double‐negative with POU2F3 expression (SCLC‐P), and negative for all three markers (SCLC‐I). In whole slides, 40 SCLC‐A (52%), 20 SCLC‐N (26%), 15 SCLC‐P (20%), and two SCLC‐I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P = 0.0047; NEUROD1, P = 0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens.
Conclusion
The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients.</description><subject>ASCL1</subject><subject>ASCL1 protein</subject><subject>Basic Helix-Loop-Helix Transcription Factors</subject><subject>Beta2 protein</subject><subject>Biopsy</subject><subject>Cell Line, Tumor</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Lung carcinoma</subject><subject>Lung Neoplasms - genetics</subject><subject>Lymph nodes</subject><subject>Lymphatic Metastasis</subject><subject>Lymphatic system</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>NEUROD1</subject><subject>Octamer Transcription Factors - metabolism</subject><subject>POU2F3</subject><subject>small cell carcinoma</subject><subject>Small cell lung carcinoma</subject><subject>Small Cell Lung Carcinoma - genetics</subject><subject>Tumors</subject><issn>0309-0167</issn><issn>1365-2559</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd9qFDEUh4Modlu98AUk4I2FTpszmUw2l2VtbWFxxbrXQzbJtCnzrzk76DyRr-lpp3ohGEISko8vh_Nj7B2IU6BxdhfxFIqlzl-wBchSZblS5iVbCClMJqDUB-wQ8V4I0DLPX7MDWWpQSssF-7Xq28GmiH3H-5qf36zWcMK_XGy_bT7RwXaef91s80vJw88hBcRIYOw4juk2Ots0E6fb4PbBcxyCi23o8IQPNia62UfEMfA2utTblOyEs7KZ2uGOd72nt7C3SDPgk7YlJXeBlmbsbrmzycWub-0b9qq2DYa3z_sR215efF9dZevN5-vV-TpzUsk80wA7tQOwUhmtlo66IQovtPZO6ryuzdJLA9b7nRK-MCBVmddgjCl2qihLI4_Yx9k7pP5hDLiv2oiP9dgu9CNWudYgjBBCE_rhH_S-H1NH1RFl6JsCBBB1PFPUAsQU6mpIsbVpqkBUj-lVlF71lB6x75-N464N_i_5Jy4CzmbgR2zC9H9TdXV9Myt_AxDRoqs</recordid><startdate>202305</startdate><enddate>202305</enddate><creator>Handa, Takafumi</creator><creator>Hayashi, Takuo</creator><creator>Ura, Ayako</creator><creator>Watanabe, Isamu</creator><creator>Takamochi, Kazuya</creator><creator>Onagi, Hiroko</creator><creator>Kishi, Monami</creator><creator>Matsumoto, Naohisa</creator><creator>Tajima, Ken</creator><creator>Kishikawa, Satsuki</creator><creator>Saito, Tsuyoshi</creator><creator>Takahashi, Kazuhisa</creator><creator>Suzuki, Kenji</creator><creator>Yao, Takashi</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9690-8440</orcidid><orcidid>https://orcid.org/0000-0002-8544-9370</orcidid></search><sort><creationdate>202305</creationdate><title>Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma</title><author>Handa, Takafumi ; Hayashi, Takuo ; Ura, Ayako ; Watanabe, Isamu ; Takamochi, Kazuya ; Onagi, Hiroko ; Kishi, Monami ; Matsumoto, Naohisa ; Tajima, Ken ; Kishikawa, Satsuki ; Saito, Tsuyoshi ; Takahashi, Kazuhisa ; Suzuki, Kenji ; Yao, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3532-711b5b11a359758c13604d077dc372ff98d391addb50d4913562f19994b546693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>ASCL1</topic><topic>ASCL1 protein</topic><topic>Basic Helix-Loop-Helix Transcription Factors</topic><topic>Beta2 protein</topic><topic>Biopsy</topic><topic>Cell Line, Tumor</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Lung carcinoma</topic><topic>Lung Neoplasms - genetics</topic><topic>Lymph nodes</topic><topic>Lymphatic Metastasis</topic><topic>Lymphatic system</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>NEUROD1</topic><topic>Octamer Transcription Factors - metabolism</topic><topic>POU2F3</topic><topic>small cell carcinoma</topic><topic>Small cell lung carcinoma</topic><topic>Small Cell Lung Carcinoma - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Handa, Takafumi</creatorcontrib><creatorcontrib>Hayashi, Takuo</creatorcontrib><creatorcontrib>Ura, Ayako</creatorcontrib><creatorcontrib>Watanabe, Isamu</creatorcontrib><creatorcontrib>Takamochi, Kazuya</creatorcontrib><creatorcontrib>Onagi, Hiroko</creatorcontrib><creatorcontrib>Kishi, Monami</creatorcontrib><creatorcontrib>Matsumoto, Naohisa</creatorcontrib><creatorcontrib>Tajima, Ken</creatorcontrib><creatorcontrib>Kishikawa, Satsuki</creatorcontrib><creatorcontrib>Saito, Tsuyoshi</creatorcontrib><creatorcontrib>Takahashi, Kazuhisa</creatorcontrib><creatorcontrib>Suzuki, Kenji</creatorcontrib><creatorcontrib>Yao, Takashi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Histopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Handa, Takafumi</au><au>Hayashi, Takuo</au><au>Ura, Ayako</au><au>Watanabe, Isamu</au><au>Takamochi, Kazuya</au><au>Onagi, Hiroko</au><au>Kishi, Monami</au><au>Matsumoto, Naohisa</au><au>Tajima, Ken</au><au>Kishikawa, Satsuki</au><au>Saito, Tsuyoshi</au><au>Takahashi, Kazuhisa</au><au>Suzuki, Kenji</au><au>Yao, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma</atitle><jtitle>Histopathology</jtitle><addtitle>Histopathology</addtitle><date>2023-05</date><risdate>2023</risdate><volume>82</volume><issue>6</issue><spage>860</spage><epage>869</epage><pages>860-869</pages><issn>0309-0167</issn><eissn>1365-2559</eissn><abstract>Aims
Subtypes of small cell lung carcinoma (SCLC) are defined by the expression of ASCL1, NEUROD1, and POU2F3 markers. The aim of our study was to explore the extent to which the intratumoral heterogeneity of ASCL1, NEUROD1, and POU2F3 may lead to discrepancies in expression of these markers in surgical samples and their matched tissue microarray (TMA) and lymph node (LN) metastatic sites.
Methods and results
The cohort included 77 patients with SCLC. Immunohistochemical examinations were performed on whole slides of the primary tumour, paired TMAs, and metastatic LN sites. Samples with H‐scores >50 were considered positive. Based on the ASCL1, NEUROD1, and POU2F3 staining pattern, we grouped the tumours as follows: ASCL1‐dominant (SCLC‐A), NEUROD1‐dominant (SCLC‐N), ASCL1/NEUROD1 double‐negative with POU2F3 expression (SCLC‐P), and negative for all three markers (SCLC‐I). In whole slides, 40 SCLC‐A (52%), 20 SCLC‐N (26%), 15 SCLC‐P (20%), and two SCLC‐I (3%) tumours were identified. Comparisons of TMAs or LN metastatic sites and corresponding surgical specimens showed that positivity for ASCL1, NEUROD1, and POU2F3 in TMAs (all P < 0.0001) or LN metastatic sites (ASCL1, P = 0.0047; NEUROD1, P = 0.0069; POU2F3, P < 0.0001) correlated significantly with that of corresponding surgical specimens.
Conclusion
The positivity for these markers in TMAs and LN metastatic sites was significantly correlated with that of corresponding surgical specimens, indicating that biopsy specimens could be used to identify molecular subtypes of SCLC in patients.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36715573</pmid><doi>10.1111/his.14872</doi><tpages>869</tpages><orcidid>https://orcid.org/0000-0001-9690-8440</orcidid><orcidid>https://orcid.org/0000-0002-8544-9370</orcidid></addata></record> |
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| subjects | ASCL1 ASCL1 protein Basic Helix-Loop-Helix Transcription Factors Beta2 protein Biopsy Cell Line, Tumor Gene Expression Regulation, Neoplastic Humans Lung carcinoma Lung Neoplasms - genetics Lymph nodes Lymphatic Metastasis Lymphatic system Metastases Metastasis NEUROD1 Octamer Transcription Factors - metabolism POU2F3 small cell carcinoma Small cell lung carcinoma Small Cell Lung Carcinoma - genetics Tumors |
| title | Comparison of ASCL1, NEUROD1, and POU2F3 expression in surgically resected specimens, paired tissue microarrays, and lymph node metastases in small cell lung carcinoma |
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