Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy
•Positive MYC immunostaining is an independent predictor of survival after immunotherapy.•MYC positive and PD-L1 negative cases had shortest overall survival.•MYC copy number gain was not predictive of MYC immunostaining or survival differences.•MYC immunohistochemistry may be of relevance to lung c...
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description | •Positive MYC immunostaining is an independent predictor of survival after immunotherapy.•MYC positive and PD-L1 negative cases had shortest overall survival.•MYC copy number gain was not predictive of MYC immunostaining or survival differences.•MYC immunohistochemistry may be of relevance to lung cancer treatment selection.
Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value.
MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation.
Nine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1–6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15–0.72, P=0.0055). MYC IHC positive/PD-L1 |
doi_str_mv | 10.1016/j.lungcan.2024.107927 |
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Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value.
MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation.
Nine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1–6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15–0.72, P=0.0055). MYC IHC positive/PD-L1 < 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). MYC CNG was not associated with OS or PFS.
We find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 < 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.</description><identifier>ISSN: 0169-5002</identifier><identifier>ISSN: 1872-8332</identifier><identifier>EISSN: 1872-8332</identifier><identifier>DOI: 10.1016/j.lungcan.2024.107927</identifier><identifier>PMID: 39173231</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Amplification ; B7-H1 Antigen - genetics ; B7-H1 Antigen - metabolism ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Carcinoma, Non-Small-Cell Lung - genetics ; Carcinoma, Non-Small-Cell Lung - metabolism ; Carcinoma, Non-Small-Cell Lung - mortality ; Carcinoma, Non-Small-Cell Lung - pathology ; Carcinoma, Non-Small-Cell Lung - therapy ; Copy number gain ; DNA Copy Number Variations ; Female ; Humans ; Immunohistochemistry ; Immunotherapy ; Immunotherapy - methods ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Lung Neoplasms - therapy ; Male ; Middle Aged ; Mutation ; MYC ; Non-small cell lung cancer ; PD-L1 ; Predictive Value of Tests ; Prognosis ; Proto-Oncogene Proteins c-myc - genetics ; Proto-Oncogene Proteins c-myc - metabolism ; Retrospective Studies</subject><ispartof>Lung cancer (Amsterdam, Netherlands), 2024-09, Vol.195, p.107927, Article 107927</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c243t-d7680e5933d8b9d66a7b9af11018d5469e7109355162e6733a05e0e15268d03f3</cites><orcidid>0009-0003-1374-9571 ; 0000-0002-8514-9861 ; 0000-0002-8893-0645 ; 0000-0002-7799-7860 ; 0000-0002-2943-3817 ; 0000-0003-1974-0175</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.lungcan.2024.107927$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39173231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naso, Julia</creatorcontrib><creatorcontrib>Desai, Aakash</creatorcontrib><creatorcontrib>Smith, Caleb J.</creatorcontrib><creatorcontrib>Ashara, Yash P.</creatorcontrib><creatorcontrib>Yip, Stephen</creatorcontrib><creatorcontrib>Lo, Ying-Chun</creatorcontrib><title>Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy</title><title>Lung cancer (Amsterdam, Netherlands)</title><addtitle>Lung Cancer</addtitle><description>•Positive MYC immunostaining is an independent predictor of survival after immunotherapy.•MYC positive and PD-L1 negative cases had shortest overall survival.•MYC copy number gain was not predictive of MYC immunostaining or survival differences.•MYC immunohistochemistry may be of relevance to lung cancer treatment selection.
Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value.
MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation.
Nine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1–6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15–0.72, P=0.0055). MYC IHC positive/PD-L1 < 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). MYC CNG was not associated with OS or PFS.
We find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 < 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Amplification</subject><subject>B7-H1 Antigen - genetics</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - genetics</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Carcinoma, Non-Small-Cell Lung - mortality</subject><subject>Carcinoma, Non-Small-Cell Lung - pathology</subject><subject>Carcinoma, Non-Small-Cell Lung - therapy</subject><subject>Copy number gain</subject><subject>DNA Copy Number Variations</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - mortality</subject><subject>Lung Neoplasms - pathology</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>MYC</subject><subject>Non-small cell lung cancer</subject><subject>PD-L1</subject><subject>Predictive Value of Tests</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>Proto-Oncogene Proteins c-myc - metabolism</subject><subject>Retrospective Studies</subject><issn>0169-5002</issn><issn>1872-8332</issn><issn>1872-8332</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU2vEyEUhonReOvVn6Bh6WYqHwVmVsY0fiXX6EIXrgiFM7c0A1RgavpL_Lsytro1IZyEvO855-VB6Dkla0qofHVYT3O8tyauGWGb9qYGph6gFe0V63rO2UO0arqhE4SwG_SklAMhVFEyPEY3fKCKM05X6NeXDM7b6k-AT2aaAZvocEgT2HkyGduUM0ymQsFpxJ--b7EPYY5p70tNdg-h1Xz-Y7LpeMZxDjvI-N74iNuJKXYlmGnCFtq1rIytydbHFEzBNUNr7fBPX_fXxnUP2RzPT9Gj0UwFnl3rLfr27u3X7Yfu7vP7j9s3d51lG147p2RPQAycu343OCmN2g1mpO2Leic2coAlMReCSgZScW6IAAJUMNk7wkd-i15e-h5z-jFDqbolWnY1EdJcNCeDZKpXVDSpuEhtTqVkGPUx-2DyWVOiFyb6oK9M9MJEX5g034vriHkXwP1z_YXQBK8vAmhBTx6yLtZDtA1MBlu1S_4_I34DJeCibw</recordid><startdate>202409</startdate><enddate>202409</enddate><creator>Naso, Julia</creator><creator>Desai, Aakash</creator><creator>Smith, Caleb J.</creator><creator>Ashara, Yash P.</creator><creator>Yip, Stephen</creator><creator>Lo, Ying-Chun</creator><general>Elsevier B.V</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>7X8</scope><orcidid>https://orcid.org/0009-0003-1374-9571</orcidid><orcidid>https://orcid.org/0000-0002-8514-9861</orcidid><orcidid>https://orcid.org/0000-0002-8893-0645</orcidid><orcidid>https://orcid.org/0000-0002-7799-7860</orcidid><orcidid>https://orcid.org/0000-0002-2943-3817</orcidid><orcidid>https://orcid.org/0000-0003-1974-0175</orcidid></search><sort><creationdate>202409</creationdate><title>Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy</title><author>Naso, Julia ; Desai, Aakash ; Smith, Caleb J. ; Ashara, Yash P. ; Yip, Stephen ; Lo, Ying-Chun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c243t-d7680e5933d8b9d66a7b9af11018d5469e7109355162e6733a05e0e15268d03f3</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>Amplification</topic><topic>B7-H1 Antigen - genetics</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - genetics</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Carcinoma, Non-Small-Cell Lung - mortality</topic><topic>Carcinoma, Non-Small-Cell Lung - pathology</topic><topic>Carcinoma, Non-Small-Cell Lung - therapy</topic><topic>Copy number gain</topic><topic>DNA Copy Number Variations</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Immunotherapy - methods</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - mortality</topic><topic>Lung Neoplasms - pathology</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>MYC</topic><topic>Non-small cell lung cancer</topic><topic>PD-L1</topic><topic>Predictive Value of Tests</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>Proto-Oncogene Proteins c-myc - metabolism</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naso, Julia</creatorcontrib><creatorcontrib>Desai, Aakash</creatorcontrib><creatorcontrib>Smith, Caleb J.</creatorcontrib><creatorcontrib>Ashara, Yash P.</creatorcontrib><creatorcontrib>Yip, Stephen</creatorcontrib><creatorcontrib>Lo, Ying-Chun</creatorcontrib><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>Lung cancer (Amsterdam, Netherlands)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naso, Julia</au><au>Desai, Aakash</au><au>Smith, Caleb J.</au><au>Ashara, Yash P.</au><au>Yip, Stephen</au><au>Lo, Ying-Chun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy</atitle><jtitle>Lung cancer (Amsterdam, Netherlands)</jtitle><addtitle>Lung Cancer</addtitle><date>2024-09</date><risdate>2024</risdate><volume>195</volume><spage>107927</spage><pages>107927-</pages><artnum>107927</artnum><issn>0169-5002</issn><issn>1872-8332</issn><eissn>1872-8332</eissn><abstract>•Positive MYC immunostaining is an independent predictor of survival after immunotherapy.•MYC positive and PD-L1 negative cases had shortest overall survival.•MYC copy number gain was not predictive of MYC immunostaining or survival differences.•MYC immunohistochemistry may be of relevance to lung cancer treatment selection.
Accurately predicting which patients diagnosed with non-small cell lung cancer (NSCLC) will respond to immunotherapy remains a clinical challenge. This study aims to determine the associations between MYC immunoreactivity, MYC copy number gain (CNG), driver mutations and survival following immunotherapy treatment, to provide insight into whether clinical MYC assessment may have predictive value.
MYC copy number status was determined in 82 patients with NSCLC treated with immunotherapy, and MYC immunohistochemistry (IHC) was performed on 80 of these cases. MYC staining in ≥ 40 % of tumor cells was considered positive. Driver gene alterations, PD-L1 status and survival outcomes were assessed through retrospective chart review. Overall survival (OS) and progression free survival (PFS) were calculated from the date of immunotherapy initiation.
Nine (11 %) of 82 cases had MYC CNG and 56 (70 %) of the 80 immunostained cases were positive for MYC. MYC CNG was significantly associated with STK11 mutation (P=0.023), whereas positive MYC IHC was significantly associated with KRAS mutation (P=0.0076) and current/former smoking (P=0.0007). MYC CNG and positive MYC IHC were not significantly associated with each other (P=0.42), or with PD-L1 ≥ 1 % (MYC CNG: P=0.10; MYC IHC: P=0.09). Positive MYC IHC and PD-L1 ≥ 1 % were both significant predictors of OS (MYC: HR 2.7, 95 % CI 1.1–6.4, P=0.026; PD-L1: HR 0.33, 95 % CI 0.15–0.72, P=0.0055). MYC IHC positive/PD-L1 < 1 % cases had the shortest OS (median 230 versus 918 days, P=0.00069) and PFS (median 84 versus 254 days, P=0.0087). MYC CNG was not associated with OS or PFS.
We find that positive MYC IHC is an independent predictor of shorter OS after immunotherapy treatment, with MYC positive/PD-L1 < 1 % status predictive of particularly poor immunotherapy response. We identify positive MYC IHC as a feature of possible relevance to NSCLC treatment selection and of interest for future therapy development.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>39173231</pmid><doi>10.1016/j.lungcan.2024.107927</doi><orcidid>https://orcid.org/0009-0003-1374-9571</orcidid><orcidid>https://orcid.org/0000-0002-8514-9861</orcidid><orcidid>https://orcid.org/0000-0002-8893-0645</orcidid><orcidid>https://orcid.org/0000-0002-7799-7860</orcidid><orcidid>https://orcid.org/0000-0002-2943-3817</orcidid><orcidid>https://orcid.org/0000-0003-1974-0175</orcidid></addata></record> |
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subjects | Adult Aged Aged, 80 and over Amplification B7-H1 Antigen - genetics B7-H1 Antigen - metabolism Biomarkers, Tumor - genetics Biomarkers, Tumor - metabolism Carcinoma, Non-Small-Cell Lung - genetics Carcinoma, Non-Small-Cell Lung - metabolism Carcinoma, Non-Small-Cell Lung - mortality Carcinoma, Non-Small-Cell Lung - pathology Carcinoma, Non-Small-Cell Lung - therapy Copy number gain DNA Copy Number Variations Female Humans Immunohistochemistry Immunotherapy Immunotherapy - methods Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - mortality Lung Neoplasms - pathology Lung Neoplasms - therapy Male Middle Aged Mutation MYC Non-small cell lung cancer PD-L1 Predictive Value of Tests Prognosis Proto-Oncogene Proteins c-myc - genetics Proto-Oncogene Proteins c-myc - metabolism Retrospective Studies |
title | Predictive value and molecular correlates of MYC immunohistochemistry and copy number gain in non-small cell lung carcinomas treated with immunotherapy |
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