{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:57:13Z","timestamp":1787014633121,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,12,6]],"date-time":"2007-12-06T00:00:00Z","timestamp":1196899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2008,1]]},"abstract":"<jats:p>\n                    Although the histogenesis of sclerosing hemangioma (SH) of the lung is now thought to be respiratory epithelial in origin, the genetic abnormalities that mediate its development are not known. Because pathophysiology of several syndromes associated with benign tumors may converge on the tuberous sclerosis complex (TSC), serine\/threonine kinase 11 (STK11), and mammalian target of rapamycin (mTOR) pathways, the purpose of the present paper was to investigate their roles in the development of SH. Semiquantitative immunohistochemical analysis was done to assess the expression of phospho\u2010mTOR, phospho\u2010S6 ribosomal protein, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phospho\u2010Akt, STK11, tuberin, hamartin, vascular endothelial growth factor (VEGF), and hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) in 19 cases of typical SH. To determine whether genetic alteration of\n                    <jats:italic>STK11<\/jats:italic>\n                    is involved in the development of SH, all encoding exons of\n                    <jats:italic>STK11<\/jats:italic>\n                    were analyzed by polymerase chain reaction (PCR) amplification and direct sequencing of genomic DNA of six specimens. The six specimens were also investigated for whether promoter hypermethylation exists as an alternative inactivating mechanism for\n                    <jats:italic>STK11<\/jats:italic>\n                    . All specimens showed moderate to marked reaction to phospho\u2010S6 ribosomal protein and PTEN; 16 specimens (84%) showed slight to moderate reaction to phospho\u2010mTOR, negative reaction to STK11, and slight to moderate reaction to hamartin; 11 (58%) showed slight to moderate reaction to phospho\u2010Akt; 18 (95%) showed slight to moderate reaction to tuberin and positive reaction for HIF\u20101\u03b1; and 17 (90%) showed moderate reaction to VEGF. No somatic mutation of\n                    <jats:italic>STK11<\/jats:italic>\n                    was found and the six specimens were unmethylated in the promoter region. These data imply that aberrant mTOR signaling may play a role in the development of SH, and its vascular nature may be due partially to high levels of VEGF caused by dysregulation of mTOR signaling.\n                  <\/jats:p>","DOI":"10.1111\/j.1440-1827.2007.02186.x","type":"journal-article","created":{"date-parts":[[2010,8,12]],"date-time":"2010-08-12T08:30:00Z","timestamp":1281601800000},"page":"38-44","source":"Crossref","is-referenced-by-count":23,"title":["Role of the PI3K\/Akt, mTOR, and STK11\/LKB1 pathways in the tumorigenesis of sclerosing hemangioma of the lung"],"prefix":"10.1111","volume":"58","author":[{"given":"Randa M. 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