{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T12:42:55Z","timestamp":1786624975571,"version":"build-2736575974"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T00:00:00Z","timestamp":1743120000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The micropapillary (MIP) pattern is a high\u2010grade histological subtype of lung adenocarcinoma (LUAD) with poor prognosis. In this study, surgically resected tumor samples from 101 patients with stage I\u2013III MIP\u2013LUAD (MIP \u226530%) were microdissected to separate MIP components from non\u2010MIP components, all of which underwent RNA and DNA whole\u2010exome sequencing (WES). The genomic and transcriptomic landscapes of MIP and non\u2010MIP components within MIP\u2010enriched tumor tissues demonstrated remarkable similarities, notably marked by high epidermal growth factor receptor (EGFR) alteration frequencies. However, when compared to MIP\u2010na\u00efve LUAD tissues, MIP components showed higher chromosomal instability and revealed 18 enriched alterations, encompassing EGFR mutations, EGFR amplifications, and CDKN2A\/CDKN2B deletions, which all linked to upregulation of cell proliferation pathways and downregulation of immune pathways. Shared mutations were observed in 97.8% (91\/93) of patients with paired DNA WES data for MIP and non\u2010MIP components within the same tissues, suggesting a common origin. The recurrence\u2010free survival analysis identified MACF1, PCLO, ADGRV1, and Fanconi Anemia pathway mutations as negative indicators. In all, we conducted an in\u2010depth analysis of the molecular characteristics and transformation mechanisms of MIP\u2013LUAD, employing microdissection techniques to investigate the genomic and transcriptomic levels within a substantial cohort, providing insights for precision medicine of this aggressive cancer subtype. \u00a9 2025 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.6416","type":"journal-article","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T15:32:39Z","timestamp":1743348759000},"page":"204-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multi\u2010omics analyses reveal distinct molecular characteristics and transformation mechanisms of stage I\u2013<scp>III<\/scp> micropapillary lung adenocarcinoma"],"prefix":"10.1002","volume":"266","author":[{"given":"Yang","family":"Qu","sequence":"first","affiliation":[{"name":"Department of Pathology, 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