Beta-catenin mutations in pulmonary blastomas: association with morule formation.
To elucidate the contribution of beta-catenin gene mutation to the development of pulmonary blastomas, we analysed mutations in three well-differentiated fetal adenocarcinomas (WDFAs) and six biphasic pulmonary blastomas (BPBs). For comparison, eight clear-cell adenocarcinomas with fetal lung features were also examined. beta-Catenin gene mutations were found in all three WDFAs, two BPBs, and none of the clear-cell adenocarcinomas with fetal lung features. All tumours with mutations had a common histological feature, namely morule formation, and showed a characteristic heterogeneous beta-catenin expression pattern that was revealed by immunohistochemistry. Strong nuclear/cytoplasmic expression of beta-catenin was seen in clustered cells in the morular areas and in single cells in glands, and was associated with neuroendocrine differentiation. As beta-catenin mutations are rare among lung tumours, this distinctive genetic feature, which is also immunohistochemically detectable as overexpression with a heterogeneous pattern, has diagnostic significance. The presence of this common genetic alteration found in both WDFA and BPB implies a histogenetic linkage between these tumours.
Sekine
Shigeki
S
Pathology Division, National Cancer Center Research Institute and Hospital, Tokyo, Japan.
Shibata
Tatsuhiro
T
Matsuno
Yoshihiro
Y
Maeshima
Arafumi
A
Ishii
Genichiro
G
Sakamoto
Michiie
M
Hirohashi
Setsuo
S
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018262:Adenocarcinoma, Clear Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis / Q000379:methods; D004273:DNA, Neoplasm / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009028:Morula / Q000473:pathology*; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D018202:Pulmonary Blastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin