{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:12:50Z","timestamp":1788469970831,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Lung cancer complicated by malignant pleural effusions (MPEs) is associated with significantly increased morbidity and mortality, yet the mechanisms of MPE development remain poorly understood. This study sought to elucidate whether there were specific genomic alterations and\/or immunologic biomarkers associated with the presence of MPEs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Analysis of comprehensive genomic and immunologic profiling for 275 locally advanced (stage III) or advanced (stage IV) lung adenocarcinomas was subcategorized into cytology\u2010confirmed MPE\u2010positive (MPE+; <jats:italic>n<\/jats:italic>\u00a0=\u00a0139 stage IV) and MPE\u2010negative (MPE\u2212; <jats:italic>n<\/jats:italic>\u00a0=\u00a030 stage III\u00a0+\u00a0<jats:italic>n<\/jats:italic>\u00a0=\u00a0106 stage IV) groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Smoking frequency (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.0001) and tumor mutational burden (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) were demonstrated to be lower in the MPE+\u00a0group compared to the MPE\u2212 group. Median overall survival in the MPE+\u00a0group was shorter than in the MPE\u2212 group across all data (2.0 vs. 5.5 years; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.0001) and for smokers (1.2 vs. 6.4 years; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.0001). There were a number of differences at the genomic level across all cases and when stratifying by smoking status, including a higher frequency of <jats:italic>EGFR<\/jats:italic> mutations and a lower frequency of <jats:italic>STK11<\/jats:italic> mutations in the MPE+\u00a0cohort. Finally, investigation of the comutational profiles of tumors by MPE status revealed differences in <jats:italic>TP53<\/jats:italic>\u2010 and <jats:italic>STK11<\/jats:italic>\u2010mutant tumors between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, these findings imply that there are both clinical and genetic factors associated with advanced lung adenocarcinoma MPEs. Future studies of these alterations may prove important both for understanding the pathophysiology of MPE development in advanced cancer and for the earlier detection of at\u2010risk patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22900","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:36:49Z","timestamp":1724931409000},"page":"788-798","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparative genomic and immunopathologic analysis of lung adenocarcinomas with and without cytology\u2010proven malignant pleural effusions"],"prefix":"10.1002","volume":"132","author":[{"given":"Cristiana M.","family":"Pineda","sequence":"first","affiliation":[{"name":"Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adnan","family":"Majid","sequence":"additional","affiliation":[{"name":"Division of Thoracic Surgery and Interventional Pulmonology Department of Surgery Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel B.","family":"Costa","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology Department of Medicine Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7234-5652","authenticated-orcid":false,"given":"Paul A.","family":"VanderLaan","sequence":"additional","affiliation":[{"name":"Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820"},{"key":"e_1_2_8_3_1","unstructured":"Cancer Stat Facts: Lung and Bronchus Cancer. 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