Mutations in the p53 gene in pulmonary blastomas: Immunohistochemical and molecular studies

Abstract

Well-differentiated fetal adenocarcinomas and biphasic blastomas are types of lung cancer that contain glands that mimic the appearance of fetal lung. Biphasic blastomas also show a primitive embryonic stroma. Despite histological similarities leading these two tumors to be classified as pulmonary blastomas, they have distinct clinical and prognostic features. Little information is available on genetic changes in these tumors because they are rare; therefore, the authors studied nine biphasic blastomas and 12 well-differentiated fetal adenocarcinomas for the presence of mutations in the p53 gene. Mutations in the p53 gene are common in other lung cancers, and the type of mutation in the p53 gene can provide information about the original or inciting mutagens. The authors found five biphasic blastomas (42%) had mutations in the p53 gene by immunohistochemical and molecular analysis, whereas none of the well-differentiated fetal adenocarcinomas contained mutations. These results provide molecular support for the significance of distinguishing between well-differentiated fetal adenocarcinoma and biphasic blastoma histologically and identify several types of p53 gene mutations that occur in these tumors.

Clonality and heterogeneity of pulmonary blastoma from the viewpoint of genetic alterations: A case report

“…Recent molecular studies of theˇ-catenin gene have strongly indicated that both epithelial and mesenchymal components originate from a single clone, since the same types ofˇ-catenin mutations were detected in both components of individual tumors [5]. On the other hand, results of mutational analyses for the p53 gene are not consistent among the reports [6][7][8]. Heterogeneity as well as homogeneity for mutations and expression of the p53 gene have been shown between the epithelial and mesenchymal components.…”

K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung

“…These tumors may be differentiated from carcinosarcomas for the lack of a true malignant heterologous mesenchymal component, such as bone, cartilage, vessels or skeletal muscle, 10 and from pulmonary blastomas for the lack of primitive mesenchymal and epithelial tumor cells. 1,20 Pleomorphic carcinomas are basically thought to be epithelial tumors in which neoplastic cells undergo an epithelial-mesenchymal transition 21 and express vimentin and other mesenchymal proteins. 3,7,[13][14][15]17,19,22 In different anatomical sites, most, but not all, of these tumors composed of carcinoma and sarcoma or sarcoma-like components are considered monoclonal growths (the so-called divergent hypothesis) rather than true collision tumors (convergent hypothesis).…”

“…3,7,[13][14][15]17,19,22 In different anatomical sites, most, but not all, of these tumors composed of carcinoma and sarcoma or sarcoma-like components are considered monoclonal growths (the so-called divergent hypothesis) rather than true collision tumors (convergent hypothesis). 20,[23][24][25][26][27][28][29][30][31] In turn, these monoclonal growths may originate from a single ancestor undergoing divergent epithelial and mesenchymal differentiation early during the neoplastic transformation (combination theory), or the full-blown carcinoma cells undergo sarcomatoid changes during tumor progression (conversion theory). 21,[23][24][25] In the lung, a monoclonal origin has been suggested for carcinosarcoma and blastoma using diverse molecular strategies, such as X chromosome inactivation, 24 microsatellite analysis, 29 and mutational genotyping of p53 gene, 28 whereas little is known about clonality of pulmonary pleomorphic carcinomas.…”

Pulmonary Blastoma: Report of Two Cases

“…The PPB seems to be associated with a chromosome 2 trisomy, 7 whereas CBPB and WDFA have shown p53 gene mutations and/or p53 protein overexpression. [8][9][10] Although the correlation to smoking is still unclear, according to two reports 1,5 82% and 79% of the patients were found to be smokers, supporting the theory that smoking can be implicated in the development of these malignancies. Both of our patients were heavy smokers.…”