PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site
Background Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its...
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| Veröffentlicht in: | International journal of clinical oncology 2024-06, Vol.29 (6), p.726-734 |
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| creator | Junior, João Neif Antonio Preto, Daniel D.’Almeida Lazarini, Maria Eduarda Zanatta Neder de Lima, Marcos Alves Bonatelli, Murilo Berardinelli, Gustavo Noriz da Silva, Vinicius Duval Pinheiro, Céline Reis, Rui Manuel Cárcano, Flavio Mavignier |
| description | Background
Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features.
Methods
The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis.
Results
Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months,
p
-value: |
| doi_str_mv | 10.1007/s10147-024-02494-3 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11130030</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3060577531</sourcerecordid><originalsourceid>FETCH-LOGICAL-c475t-310b80006bb4e72a4ede0572064ab9360e26a1b00d20d4cc6173222dafd45e753</originalsourceid><addsrcrecordid>eNp9kclOIzEQhi00iP0FOCBLc4FDQ3lrJyc0YpeCQALE0XJ3VxhDYmfsbpa3xyEBBg4cLJdcX_1V5Z-QTQa7DEDvJQZM6gK4nJ6-LMQCWWFS6EJrzX_lWEhW9EuulslqSvcATJeKL5Fl0VO8x_tyhdxeHhYDRvF5EjElFzy1vqFjV8eQbIujkWuROp9aW7kcv9Dt86uznfxCa-trjDQMaecffHjydBLd2MYXmnLNOlkc2lHCjfm9Rm6Oj64PTovBxcnZwZ9BUUut2kIwqHoAUFaVRM2txAZBaQ6ltFVflIC8tKwCaDg0sq5LpgXnvLHDRirUSqyR_ZnupKvG2NTo22hHZj6KCdaZrxnv_pq78GgYYwJAQFbYnivE8K_D1JqxS3Xe3HoMXTICStAKFPQy-vsbeh-66PN-b5TSeSCWKT6jpn-YIg4_pmFgpsaZmXEmm2bejDMiF239v8dHybtTGRAzIOWUv8P42fsH2VfnZKLV</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3060577531</pqid></control><display><type>article</type><title>PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Junior, João Neif Antonio ; Preto, Daniel D.’Almeida ; Lazarini, Maria Eduarda Zanatta Neder ; de Lima, Marcos Alves ; Bonatelli, Murilo ; Berardinelli, Gustavo Noriz ; da Silva, Vinicius Duval ; Pinheiro, Céline ; Reis, Rui Manuel ; Cárcano, Flavio Mavignier</creator><creatorcontrib>Junior, João Neif Antonio ; Preto, Daniel D.’Almeida ; Lazarini, Maria Eduarda Zanatta Neder ; de Lima, Marcos Alves ; Bonatelli, Murilo ; Berardinelli, Gustavo Noriz ; da Silva, Vinicius Duval ; Pinheiro, Céline ; Reis, Rui Manuel ; Cárcano, Flavio Mavignier</creatorcontrib><description>Background
Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features.
Methods
The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis.
Results
Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months,
p
-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively).
Conclusion
PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.</description><identifier>ISSN: 1341-9625</identifier><identifier>EISSN: 1437-7772</identifier><identifier>DOI: 10.1007/s10147-024-02494-3</identifier><identifier>PMID: 38528294</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Adult ; Aged ; Aged, 80 and over ; B7-H1 Antigen - genetics ; Biomarkers, Tumor - genetics ; Cancer ; Cancer Research ; Female ; Humans ; Immunohistochemistry ; Immunotherapy ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Metastasis ; Microsatellite Instability ; Middle Aged ; Neoplasms, Unknown Primary - genetics ; Neoplasms, Unknown Primary - pathology ; Oncology ; Original ; Original Article ; Prognosis ; Surgical Oncology ; Tumor Microenvironment</subject><ispartof>International journal of clinical oncology, 2024-06, Vol.29 (6), p.726-734</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><citedby>FETCH-LOGICAL-c475t-310b80006bb4e72a4ede0572064ab9360e26a1b00d20d4cc6173222dafd45e753</citedby><cites>FETCH-LOGICAL-c475t-310b80006bb4e72a4ede0572064ab9360e26a1b00d20d4cc6173222dafd45e753</cites><orcidid>0000-0002-0002-3507</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10147-024-02494-3$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10147-024-02494-3$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38528294$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Junior, João Neif Antonio</creatorcontrib><creatorcontrib>Preto, Daniel D.’Almeida</creatorcontrib><creatorcontrib>Lazarini, Maria Eduarda Zanatta Neder</creatorcontrib><creatorcontrib>de Lima, Marcos Alves</creatorcontrib><creatorcontrib>Bonatelli, Murilo</creatorcontrib><creatorcontrib>Berardinelli, Gustavo Noriz</creatorcontrib><creatorcontrib>da Silva, Vinicius Duval</creatorcontrib><creatorcontrib>Pinheiro, Céline</creatorcontrib><creatorcontrib>Reis, Rui Manuel</creatorcontrib><creatorcontrib>Cárcano, Flavio Mavignier</creatorcontrib><title>PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site</title><title>International journal of clinical oncology</title><addtitle>Int J Clin Oncol</addtitle><addtitle>Int J Clin Oncol</addtitle><description>Background
Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features.
Methods
The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis.
Results
Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months,
p
-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively).
Conclusion
PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>B7-H1 Antigen - genetics</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Female</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastasis</subject><subject>Microsatellite Instability</subject><subject>Middle Aged</subject><subject>Neoplasms, Unknown Primary - genetics</subject><subject>Neoplasms, Unknown Primary - pathology</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>Prognosis</subject><subject>Surgical Oncology</subject><subject>Tumor Microenvironment</subject><issn>1341-9625</issn><issn>1437-7772</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><recordid>eNp9kclOIzEQhi00iP0FOCBLc4FDQ3lrJyc0YpeCQALE0XJ3VxhDYmfsbpa3xyEBBg4cLJdcX_1V5Z-QTQa7DEDvJQZM6gK4nJ6-LMQCWWFS6EJrzX_lWEhW9EuulslqSvcATJeKL5Fl0VO8x_tyhdxeHhYDRvF5EjElFzy1vqFjV8eQbIujkWuROp9aW7kcv9Dt86uznfxCa-trjDQMaecffHjydBLd2MYXmnLNOlkc2lHCjfm9Rm6Oj64PTovBxcnZwZ9BUUut2kIwqHoAUFaVRM2txAZBaQ6ltFVflIC8tKwCaDg0sq5LpgXnvLHDRirUSqyR_ZnupKvG2NTo22hHZj6KCdaZrxnv_pq78GgYYwJAQFbYnivE8K_D1JqxS3Xe3HoMXTICStAKFPQy-vsbeh-66PN-b5TSeSCWKT6jpn-YIg4_pmFgpsaZmXEmm2bejDMiF239v8dHybtTGRAzIOWUv8P42fsH2VfnZKLV</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Junior, João Neif Antonio</creator><creator>Preto, Daniel D.’Almeida</creator><creator>Lazarini, Maria Eduarda Zanatta Neder</creator><creator>de Lima, Marcos Alves</creator><creator>Bonatelli, Murilo</creator><creator>Berardinelli, Gustavo Noriz</creator><creator>da Silva, Vinicius Duval</creator><creator>Pinheiro, Céline</creator><creator>Reis, Rui Manuel</creator><creator>Cárcano, Flavio Mavignier</creator><general>Springer Nature Singapore</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><orcidid>https://orcid.org/0000-0002-0002-3507</orcidid></search><sort><creationdate>20240601</creationdate><title>PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site</title><author>Junior, João Neif Antonio ; Preto, Daniel D.’Almeida ; Lazarini, Maria Eduarda Zanatta Neder ; de Lima, Marcos Alves ; Bonatelli, Murilo ; Berardinelli, Gustavo Noriz ; da Silva, Vinicius Duval ; Pinheiro, Céline ; Reis, Rui Manuel ; Cárcano, Flavio Mavignier</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c475t-310b80006bb4e72a4ede0572064ab9360e26a1b00d20d4cc6173222dafd45e753</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>B7-H1 Antigen - genetics</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Female</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastasis</topic><topic>Microsatellite Instability</topic><topic>Middle Aged</topic><topic>Neoplasms, Unknown Primary - genetics</topic><topic>Neoplasms, Unknown Primary - pathology</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>Prognosis</topic><topic>Surgical Oncology</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Junior, João Neif Antonio</creatorcontrib><creatorcontrib>Preto, Daniel D.’Almeida</creatorcontrib><creatorcontrib>Lazarini, Maria Eduarda Zanatta Neder</creatorcontrib><creatorcontrib>de Lima, Marcos Alves</creatorcontrib><creatorcontrib>Bonatelli, Murilo</creatorcontrib><creatorcontrib>Berardinelli, Gustavo Noriz</creatorcontrib><creatorcontrib>da Silva, Vinicius Duval</creatorcontrib><creatorcontrib>Pinheiro, Céline</creatorcontrib><creatorcontrib>Reis, Rui Manuel</creatorcontrib><creatorcontrib>Cárcano, Flavio Mavignier</creatorcontrib><collection>Springer Nature OA Free Journals</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>International journal of clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Junior, João Neif Antonio</au><au>Preto, Daniel D.’Almeida</au><au>Lazarini, Maria Eduarda Zanatta Neder</au><au>de Lima, Marcos Alves</au><au>Bonatelli, Murilo</au><au>Berardinelli, Gustavo Noriz</au><au>da Silva, Vinicius Duval</au><au>Pinheiro, Céline</au><au>Reis, Rui Manuel</au><au>Cárcano, Flavio Mavignier</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site</atitle><jtitle>International journal of clinical oncology</jtitle><stitle>Int J Clin Oncol</stitle><addtitle>Int J Clin Oncol</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>29</volume><issue>6</issue><spage>726</spage><epage>734</epage><pages>726-734</pages><issn>1341-9625</issn><eissn>1437-7772</eissn><abstract>Background
Cancer of unknown primary site (CUP) is a heterogeneous group of tumors for which the origin remains unknown. Clinical outcomes might be influenced by regulatory processes in its microenvironment. Microsatellite instability (MSI) is a predictive biomarker for cancer immunotherapy and its status, as well as co-occurrence with PD-L1 expression, is poorly evaluated. We aim to evaluate the expression of PD-L1 and the status of MSI in CUP and their possible associations with clinical–pathological features.
Methods
The combined positive score (CPS) PD-L1 expression was evaluated by immunohistochemistry. MSI status was assessed using a hexa-plex marker panel by polymerase chain reaction followed by fragment analysis.
Results
Among the 166 cases, MSI analysis was conclusive in 120, with two cases being MSI positive (1.6%). PD-L1 expression was positive in 18.3% of 109 feasible cases. PD-L1 expression was significantly associated with non-visceral metastasis and a dominance of nodal metastasis. The median overall survival (mOS) was 3.7 (95% CI 1.6–5.8) months and patients who expressed PD-L1 achieved a better mOS compared to those who did not express PD-L1 (18.7 versus 3.0 months,
p
-value: < .001). ECOG-PS equal to or more than two and PD-L1 expression were independent prognostic factors in multivariate analysis (2.37 and 0.42, respectively).
Conclusion
PD-L1 is expressed in a subset (1/5) of patients with CUP and associated with improved overall survival, while MSI is a rare event. There is a need to explore better the tumor microenvironment as well as the role of immunotherapy to change such a bad clinical outcome.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>38528294</pmid><doi>10.1007/s10147-024-02494-3</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-0002-3507</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over B7-H1 Antigen - genetics Biomarkers, Tumor - genetics Cancer Cancer Research Female Humans Immunohistochemistry Immunotherapy Male Medical prognosis Medicine Medicine & Public Health Metastasis Microsatellite Instability Middle Aged Neoplasms, Unknown Primary - genetics Neoplasms, Unknown Primary - pathology Oncology Original Original Article Prognosis Surgical Oncology Tumor Microenvironment |
| title | PD-L1 expression and microsatellite instability (MSI) in cancer of unknown primary site |
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