TY - JOUR
T1 - Microsatellite and EGFR, HER2 and K-RAS analyses in sclerosing hemangioma of the lung
AU - Sartori, Giuliana
AU - Bettelli, Stefania
AU - Schirosi, Laura
AU - Bigiani, Nazzarena
AU - Maiorana, Antonio
AU - Cavazza, Alberto
AU - Rossi, Giulio
PY - 2007/10
Y1 - 2007/10
N2 - Sclerosing hemangioma (SH) is an uncommon pulmonary tumor thought to derive from primitive respiratory epithelium consisting of 2 cell populations (cuboidal surface and polygonal stromal cells) and sharing some clinical characteristics (frequent occurrence in nonsmoking women of Asian ethnicity) with bronchioloalveolar carcinoma with which it has been suggested a possible common origin. We investigated 11 cases of SH by immunohistochemistry, fluorescence in situ hybridization, and polymerase chain reaction-based microsatellite and mutational analyses with particular emphasis on possible alterations of microsatellite loci located at tumor suppressor genes (FHIT, p16, Rb, and p53) involved in lung adenocarcinoma genesis and EGFR, HER2, and K-RAS genes. Although EGFR expression was observed in all tested cases, none showed HER2 immunostaining. Fluorescence in situ hybridization and mutational analysis of EGFR and HER2 and also K-RAS sequencing did not reveal molecular alterations, whereas allelic losses at p16 and Rb loci (4 and 2 out of 9 tested cases, respectively) with an identical microsatellite allelic loss pattern in both cuboidal and polygonal cells were observed. The finding of microsatellite alterations in chromosomal regions related to genes deeply involved in early stage lung adenocarcinoma could suggest a possible link between SH and bronchioloalveolar carcinoma, but tumor pathway promoted by EGFR, HER2, and K-RAS does not represent a common molecular mechanism of tumorigenesis. Microsatellite alterations identified in cuboidal and polygonal cells further confirm the clonal and neoplastic nature of both components of SH.
AB - Sclerosing hemangioma (SH) is an uncommon pulmonary tumor thought to derive from primitive respiratory epithelium consisting of 2 cell populations (cuboidal surface and polygonal stromal cells) and sharing some clinical characteristics (frequent occurrence in nonsmoking women of Asian ethnicity) with bronchioloalveolar carcinoma with which it has been suggested a possible common origin. We investigated 11 cases of SH by immunohistochemistry, fluorescence in situ hybridization, and polymerase chain reaction-based microsatellite and mutational analyses with particular emphasis on possible alterations of microsatellite loci located at tumor suppressor genes (FHIT, p16, Rb, and p53) involved in lung adenocarcinoma genesis and EGFR, HER2, and K-RAS genes. Although EGFR expression was observed in all tested cases, none showed HER2 immunostaining. Fluorescence in situ hybridization and mutational analysis of EGFR and HER2 and also K-RAS sequencing did not reveal molecular alterations, whereas allelic losses at p16 and Rb loci (4 and 2 out of 9 tested cases, respectively) with an identical microsatellite allelic loss pattern in both cuboidal and polygonal cells were observed. The finding of microsatellite alterations in chromosomal regions related to genes deeply involved in early stage lung adenocarcinoma could suggest a possible link between SH and bronchioloalveolar carcinoma, but tumor pathway promoted by EGFR, HER2, and K-RAS does not represent a common molecular mechanism of tumorigenesis. Microsatellite alterations identified in cuboidal and polygonal cells further confirm the clonal and neoplastic nature of both components of SH.
KW - EGFR
KW - K-RAS
KW - LOH
KW - Lung
KW - Sclerosing hemangioma
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U2 - 10.1097/PAS.0b013e318032c8cc
DO - 10.1097/PAS.0b013e318032c8cc
M3 - Article
C2 - 17895751
AN - SCOPUS:34748880057
VL - 31
SP - 1512
EP - 1520
JO - American Journal of Surgical Pathology
JF - American Journal of Surgical Pathology
SN - 0147-5185
IS - 10
ER -