Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression
Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other...
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| creator | Kwak, Yoonjin Kim, Tae-Yong Nam, Soo Kyung Hwang, Hye Jung Han, Daeyoung Oh, Hyeon Jeong Kong, Seong-Ho Park, Do Joong Oh, Do-Youn Lee, Hyuk-Joon Im, Seock-Ah Yang, Han-Kwang Lee, Hye Seung |
| description | Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other crucial GC biomarkers.
We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features.
CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P |
| doi_str_mv | 10.1093/oncolo/oyae238 |
| format | Article |
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We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features.
CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P < .001), but there was no correlation with age, sex, or stage (P > .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P < .001) and PD-L1-positive (PD-L1 CPS ≥ 5) GC (P = .014) but lower in HER2 positive GC (P = .005). CLDN18.2 positivity was not significantly associated with overall survival and disease-free survival.
This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.</description><identifier>ISSN: 1083-7159</identifier><identifier>ISSN: 1549-490X</identifier><identifier>EISSN: 1549-490X</identifier><identifier>DOI: 10.1093/oncolo/oyae238</identifier><identifier>PMID: 39306800</identifier><language>eng</language><publisher>England</publisher><ispartof>The oncologist (Dayton, Ohio), 2024-09</ispartof><rights>The Author(s) 2024. Published by Oxford University Press.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c220t-730bc5e458ae384663b18b2988fcfb35b2e977cca8b646b7c9eff4887c66ad573</cites><orcidid>0000-0002-9530-647X ; 0000-0002-1667-7986 ; 0000-0003-3495-3048</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,860,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39306800$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwak, Yoonjin</creatorcontrib><creatorcontrib>Kim, Tae-Yong</creatorcontrib><creatorcontrib>Nam, Soo Kyung</creatorcontrib><creatorcontrib>Hwang, Hye Jung</creatorcontrib><creatorcontrib>Han, Daeyoung</creatorcontrib><creatorcontrib>Oh, Hyeon Jeong</creatorcontrib><creatorcontrib>Kong, Seong-Ho</creatorcontrib><creatorcontrib>Park, Do Joong</creatorcontrib><creatorcontrib>Oh, Do-Youn</creatorcontrib><creatorcontrib>Lee, Hyuk-Joon</creatorcontrib><creatorcontrib>Im, Seock-Ah</creatorcontrib><creatorcontrib>Yang, Han-Kwang</creatorcontrib><creatorcontrib>Lee, Hye Seung</creatorcontrib><title>Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression</title><title>The oncologist (Dayton, Ohio)</title><addtitle>Oncologist</addtitle><description>Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other crucial GC biomarkers.
We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features.
CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P < .001), but there was no correlation with age, sex, or stage (P > .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P < .001) and PD-L1-positive (PD-L1 CPS ≥ 5) GC (P = .014) but lower in HER2 positive GC (P = .005). CLDN18.2 positivity was not significantly associated with overall survival and disease-free survival.
This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.</description><issn>1083-7159</issn><issn>1549-490X</issn><issn>1549-490X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNo9kD1PwzAURS0EoqWwMiKPLGntOImdEVV8VEJiAcQWvby-tEZuXOxEUH49QS1M9w733OEwdinFVIpSzXyL3vmZ3wGlyhyxscyzMslK8XY8dGFUomVejthZjO9CDFWlp2ykSiUKI8SYubmzrUW_hW49HK0scmiXfOMdYe8gcFxDAOwo2G_orG-5b3jsYEWRLxbJ4pWvIHZhwBBapMA_bbfmcwf90rZcmmnK6WsbKMaBPWcnDbhIF4ecsJe72-f5Q_L4dL-Y3zwmmKaiS7QSNeaU5QZImawoVC1NnZbGNNjUKq9TKrVGBFMXWVFrLKlpMmM0FgUsc60m7Hr_uw3-o6fYVRsbkZyDlnwfKyWF1iYvtBym0_0Ug48xUFNtg91A2FVSVL-Gq73h6mB4AK4O3329oeX__E-p-gEQVHr8</recordid><startdate>20240921</startdate><enddate>20240921</enddate><creator>Kwak, Yoonjin</creator><creator>Kim, Tae-Yong</creator><creator>Nam, Soo Kyung</creator><creator>Hwang, Hye Jung</creator><creator>Han, Daeyoung</creator><creator>Oh, Hyeon Jeong</creator><creator>Kong, Seong-Ho</creator><creator>Park, Do Joong</creator><creator>Oh, Do-Youn</creator><creator>Lee, Hyuk-Joon</creator><creator>Im, Seock-Ah</creator><creator>Yang, Han-Kwang</creator><creator>Lee, Hye Seung</creator><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9530-647X</orcidid><orcidid>https://orcid.org/0000-0002-1667-7986</orcidid><orcidid>https://orcid.org/0000-0003-3495-3048</orcidid></search><sort><creationdate>20240921</creationdate><title>Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression</title><author>Kwak, Yoonjin ; Kim, Tae-Yong ; Nam, Soo Kyung ; Hwang, Hye Jung ; Han, Daeyoung ; Oh, Hyeon Jeong ; Kong, Seong-Ho ; Park, Do Joong ; Oh, Do-Youn ; Lee, Hyuk-Joon ; Im, Seock-Ah ; Yang, Han-Kwang ; Lee, Hye Seung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c220t-730bc5e458ae384663b18b2988fcfb35b2e977cca8b646b7c9eff4887c66ad573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwak, Yoonjin</creatorcontrib><creatorcontrib>Kim, Tae-Yong</creatorcontrib><creatorcontrib>Nam, Soo Kyung</creatorcontrib><creatorcontrib>Hwang, Hye Jung</creatorcontrib><creatorcontrib>Han, Daeyoung</creatorcontrib><creatorcontrib>Oh, Hyeon Jeong</creatorcontrib><creatorcontrib>Kong, Seong-Ho</creatorcontrib><creatorcontrib>Park, Do Joong</creatorcontrib><creatorcontrib>Oh, Do-Youn</creatorcontrib><creatorcontrib>Lee, Hyuk-Joon</creatorcontrib><creatorcontrib>Im, Seock-Ah</creatorcontrib><creatorcontrib>Yang, Han-Kwang</creatorcontrib><creatorcontrib>Lee, Hye Seung</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The oncologist (Dayton, Ohio)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwak, Yoonjin</au><au>Kim, Tae-Yong</au><au>Nam, Soo Kyung</au><au>Hwang, Hye Jung</au><au>Han, Daeyoung</au><au>Oh, Hyeon Jeong</au><au>Kong, Seong-Ho</au><au>Park, Do Joong</au><au>Oh, Do-Youn</au><au>Lee, Hyuk-Joon</au><au>Im, Seock-Ah</au><au>Yang, Han-Kwang</au><au>Lee, Hye Seung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression</atitle><jtitle>The oncologist (Dayton, Ohio)</jtitle><addtitle>Oncologist</addtitle><date>2024-09-21</date><risdate>2024</risdate><issn>1083-7159</issn><issn>1549-490X</issn><eissn>1549-490X</eissn><abstract>Claudin 18.2 (CLDN18.2) is a promising target for targeted therapies in gastric cancer (GC). This study investigated the prevalence of CLDN18.2 expression in patients with stages II-IV GC or gastroesophageal junction (GEJ) adenocarcinoma and its correlation with clinicopathologic features and other crucial GC biomarkers.
We enrolled 1000 patients diagnosed with stages II-IV GC after surgical treatment. Immunohistochemistry for CLDN18 (43-14A clone), PD-L1 (22C3 pharmDx), HER2, and FGFR2 was performed. CLDN18.2 positivity was defined as moderate-to-strong (2+/3+) membranous staining in ≥75% of tumor cells. CLDN18.2 expression was compared with biomarker expression, Epstein-Barr virus (EBV) association and microsatellite instability status, and clinicopathologic features.
CLDN18.2 was positive in 34.4% of the patients. CLDN18.2 positivity was significantly higher in the middle and upper thirds than in the lower third gastric location (P < .001), but there was no correlation with age, sex, or stage (P > .05). CLDN18.2 positivity was rare (2.8%) in mucinous adenocarcinoma but frequent (90.9%) in a majority of gastric carcinomas with lymphoid stroma. CLDN18.2 positivity was higher in EBV-associated (P < .001) and PD-L1-positive (PD-L1 CPS ≥ 5) GC (P = .014) but lower in HER2 positive GC (P = .005). CLDN18.2 positivity was not significantly associated with overall survival and disease-free survival.
This study provides a comprehensive evaluation of CLDN18.2 status and its correlation with the clinicopathologic characteristics of patients with stages II-IV GC in Korea and with crucial biomarkers. It may be valuable for guiding future drug development, expanding treatment options, and ultimately improving patient outcomes in GC.</abstract><cop>England</cop><pmid>39306800</pmid><doi>10.1093/oncolo/oyae238</doi><orcidid>https://orcid.org/0000-0002-9530-647X</orcidid><orcidid>https://orcid.org/0000-0002-1667-7986</orcidid><orcidid>https://orcid.org/0000-0003-3495-3048</orcidid><oa>free_for_read</oa></addata></record> |
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| title | Clinicopathologic and molecular characterization of stages II-IV gastric cancer with Claudin 18.2 expression |
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