Copy number alterations of EGFR and FGFR1 in pulmonary carcinosarcoma2016-04-26 17:43:59
International Journal of Clinical and Experimental Pathology; 15 March 2016: ISSN:1936-2625/IJCEP0019309
Shogo Tajima, Kenji Koda
Carcinosarcoma may develop through sarcomatoid changes in a carcinoma, known as epithelial-mesenchymal transition, or may develop from a single cancer stem cell and subsequently diverge into morphologically dissimilar carcinomatous and sarcomatous components. Thus, we tried to elucidate the histogenesis of pulmonary
carcinosarcoma, which has not been thoroughly examined. A key approach to the investigation was use of fluorescence in situ hybridization analysis of EGFR and FGFR1, because the carcinomatous component of the carcinosarcoma of the available sample was a squamous cell carcinoma, which tends to harbor copy number gain in EGFR and FGFR1. Consequently, it was postulated that the carcinosarcoma originated from cancer stem cells polysomic for EGFR, and only the carcinomatous component received FGFR1 amplification during divergence into carcinomatous and sarcomatous components.
Pulmonary carcinosarcoma has been classified under sarcomatoid carcinoma, which includes four other tumor types, such as pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, and pulmonary blastoma. Pulmonary sarcomatoid carcinoma accounts for 0.1-0.4% of all lung malignancies; carcinosarcoma accounts for only 4% of sarcomatoid carcinoma. Carcinosarcoma may develop through sarcomatoid change in a carcinoma, known as epithelial-mesenchymal transition
(EMT). However, there is another opinion regarding histogenesis, in which carcinosarcoma develops from a single cancer stem cell, and subsequently diverges into morphologically dissimilar carcinomatous and sarcomatous components. It has been previously shown that both components exhibited overlapping and non-overlapping chromosomal alterations; these non-overlapping aberrations were thought to represent events significant in the divergence occurring after initial tumorigenesis.
Herein, with use of an available sample, we investigate the tumorigenesis of pulmonary carcinosarcoma having squamous cell carcinoma (SCC) as a carcinomatous component; the sarcomatous component included heterologous elements, such as rhabdomyosarcoma and osteosarcoma. We applied fluorescence in situ hybridization (FISH) analysis of EGFR and FGFR1, in addition to TP53 mutational analysis and commonly performed KRAS and EGFR mutational analyses. We had particular interest
in EGFR and FGFR1 because copy number gain in these is more frequently observed in SCC than in adenocarcinoma. Moreover, KRAS and EGFR do not often mutate in carcinosarcoma, in contrast to relatively frequent mutations in TP53. Thus, the mutational analyses of KRAS and EGFR were less interesting for the
evaluation of histogenesis. We expected that FISH analysis of EGFR and FGFR1 and mutational analysis of TP53 would reveal aspects important to the consideration of histogenesis.
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