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PD-L1 expression and CD8+ tumor-infiltrating lymphocytes are associated with ALK rearrangement and clinicopathological features in inflammatory myofibroblastic tumors

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dc.contributor.author심효섭-
dc.contributor.author차윤진-
dc.date.accessioned2018-07-20T08:38:12Z-
dc.date.available2018-07-20T08:38:12Z-
dc.date.issued2017-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/161337-
dc.description.abstractBackground: Inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms that are composed of myofibroblastic cells accompanied by inflammatory infiltrate. We investigated the immune profiles of IMTs, including PD-L1 expression and proportion of CD8+ tumor-infiltrating lymphocytes (TILs), as well as its clinicopathological characteristics according to ALK gene rearrangementstatus. Methods: Twenty-eight IMTs from 25 patients were retrieved from our pathology files (2005-2015), and their clinicopathological parameters and outcomes were analyzed. Immunohistochemistry (IHC) was performed using whole-tissue sections to detect PD-L1 and CD8 expression, and fluorescent in situ hybridization (FISH) analysis and IHC were performed using tissue microarrays to identify rearrangements in the ALK, ROS1, and RET genes. Results: ALK rearrangement was observed in 11 cases (44.0%), and all cases exhibited diffuse cytoplasmic ALK expression during IHC. ROS1 or RET rearrangement was not detected using IHC or FISH. IMTs harboring ALK rearrangement (ALK-positive) were located in the lungs (n = 7), genitourinary tract (n = 2), and mesentery (n = 1). The mean patient age was 33.2 years for ALK-positive IMTs and 53.1 years for ALK-negative IMTs. All patients with ALK-positive IMTs survived without recurrence or metastasis. IMTs with metastasis and/or recurrence were ALK-negative and exhibited elevated PD-L1 expression (positive tumor cells: 70.0% vs. 21.3%, P = 0.023; H-score: 107.5 vs. 26.3, P = 0.005). In addition, ALK-negative IMTs had a more CD8+ TILs, compared to ALK-positive IMTs (23.3% vs. 8.9%, P = 0.027). Conclusion: ALK-positive IMTs are characterized by younger age, well-defined margins, frequent involvement of the lung, and fewer CD8+ TILs. Greater PD-L1 expression was observed in IMTs with tumor necrosis and metastasis/recurrence, which were also negative for ALK rearrangement. These results suggest that immune checkpoint inhibitors may be a novel option for treating patients with advanced IMT.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherImpact Journals-
dc.relation.isPartOfONCOTARGET-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titlePD-L1 expression and CD8+ tumor-infiltrating lymphocytes are associated with ALK rearrangement and clinicopathological features in inflammatory myofibroblastic tumors-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Pathology-
dc.contributor.googleauthorYoon Jin Cha-
dc.contributor.googleauthorHyo Sup Shim-
dc.identifier.doi10.18632/oncotarget.20948-
dc.contributor.localIdA02219-
dc.contributor.localIdA04001-
dc.relation.journalcodeJ02421-
dc.identifier.eissn1949-2553-
dc.identifier.pmid29163763-
dc.subject.keywordPD-L1-
dc.subject.keywordPathology Section-
dc.subject.keywordanaplastic lymphoma kinase-
dc.subject.keywordinflammatory-
dc.subject.keywordlymphocyte-
dc.subject.keywordmyofibroblastic tumor-
dc.contributor.alternativeNameShim, Hyo Sup-
dc.contributor.alternativeNameCha, Yoon Jin-
dc.contributor.affiliatedAuthorShim, Hyo Sup-
dc.contributor.affiliatedAuthorCha, Yoon Jin-
dc.citation.volume8-
dc.citation.number52-
dc.citation.startPage89465-
dc.citation.endPage89474-
dc.identifier.bibliographicCitationONCOTARGET , Vol.8(52) : 89465-89474, 2017-
dc.identifier.rimsid61256-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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