{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:19:30Z","timestamp":1791555570125,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T00:00:00Z","timestamp":1704153600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>TP53<\/jats:italic>\n                      mutation is present in about 50.8% of lung adenocarcinomas, frequently in combination with other genetic alterations. However, a rare subset harbors the\n                      <jats:italic>TP53<\/jats:italic>\n                      mutation alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Next\u2010generation sequencing was performed in 844 lung adenocarcinomas diagnosed by fine needle aspiration. Fourteen cases (1.7%) showed isolated\n                      <jats:italic>TP53<\/jats:italic>\n                      alteration and were subjected to a comprehensive analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The average age at diagnosis was 65.7\u2009years (range 48\u201379); 9 males and 5 females. All were smokers with an average pack\u2010year of 40.7 (range 10\u201370). Ten had metastases, mostly in the brain (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094) and pleura (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20094). After a follow\u2010up period of up to 102\u2009months, 9 died, 3 were alive free of disease, 1 was alive with disease, and 1 was lost to follow\u2010up. The median survival was 12.2\u2009months. Most tumors exhibited poor differentiation, composed of solid sheets with moderate to severe atypia, increased mitotic activity, and necrotic background. Half were positive for TTF\u20101 and showed p53 overexpression. PD\u2010L1 was positive in 5 cases. Most alterations were missense mutations in exons 5\u20138, and this mutation type was associated with p53 overexpression. Tumors with combined missense mutation and truncated protein had higher PD\u2010L1 expression along with a trend towards an increase in tumor mutational burden (TMB).\n                      <jats:italic>CEBPA<\/jats:italic>\n                      deletion of undetermined significance was the most common copy number alteration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Isolated\n                      <jats:italic>TP53<\/jats:italic>\n                      mutation was seen in association with smoking, high\u2010grade cytomorphologic features, adverse prognosis, and recurrent\n                      <jats:italic>CEBPA<\/jats:italic>\n                      deletions. These tumors tend to have strong PD\u2010L1 expression and high TMB, suggesting potential benefit from immune checkpoint inhibitors. Hence, the recognition of this molecular group has prognostic and therapeutic implications.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.6873","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T03:24:26Z","timestamp":1704165866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Lung adenocarcinomas with isolated\n                    <scp>\n                      <i>TP53<\/i>\n                    <\/scp>\n                    mutation: A comprehensive clinical, cytopathologic and molecular characterization"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-2335","authenticated-orcid":false,"given":"Rachelle P.","family":"Mendoza","sequence":"first","affiliation":[{"name":"Department of Pathology University of Rochester Medical Center  Rochester New York 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