Microsatellite and EGFR, HER2 and K-RAS analyses in sclerosing hemangioma of the lung

Sclerosing hemangioma (SH) is an uncommonpulmonary tumor thought to derive from primitive respiratoryepithelium consisting of 2 cell populations (cuboidal surface andpolygonal stromal cells) and sharing some clinical characteristics(frequent occurrence in nonsmoking women of Asian ethnicity)with bronchioloalveolar carcinoma with which it has beensuggested a possible common origin. We investigated 11 cases ofSH by immunohistochemistry, fluorescence in situ hybridization,and polymerase chain reaction-based microsatellite andmutational analyses with particular emphasis on possiblealterations of microsatellite loci located at tumor suppressorgenes (FHIT, p16, Rb, and p53) involved in lung adenocarcinomagenesis and EGFR, HER2, and K-RAS genes. AlthoughEGFR expression was observed in all tested cases, none showedHER2 immunostaining. Fluorescence in situ hybridization andmutational analysis of EGFR and HER2 and also K-RASsequencing did not reveal molecular alterations, whereas alleliclosses at p16 and Rb loci (4 and 2 out of 9 tested cases,respectively) with an identical microsatellite allelic loss patternin both cuboidal and polygonal cells were observed. The findingof microsatellite alterations in chromosomal regions related togenes deeply involved in early stage lung adenocarcinoma couldsuggest a possible link between SH and bronchioloalveolarcarcinoma, but tumor pathway promoted by EGFR, HER2, andK-RAS does not represent a common molecular mechanism oftumorigenesis. Microsatellite alterations identified in cuboidaland polygonal cells further confirm the clonal and neoplasticnature of both components of SH.