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.