TY - JOUR
T1 - K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung
AU - Pelosi, Giuseppe
AU - Scarpa, Aldo
AU - Manzotti, Michela
AU - Veronesi, Giulia
AU - Spaggiari, Lorenzo
AU - Fraggetta, Filippo
AU - Nappi, Oscar
AU - Benini, Elvira
AU - Pasini, Felice
AU - Antonello, Davide
AU - Iannucci, Antonio
AU - Maisonneuve, Patrick
AU - Viale, Giuseppe
PY - 2004/5
Y1 - 2004/5
N2 - We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.
AB - We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.
KW - Clonality
KW - Histogenesis
KW - Immunohistochemistry
KW - K-ras
KW - Lung
KW - Mutation
KW - Pleomorphic carcinoma
UR - http://www.scopus.com/inward/record.url?scp=3042845278&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3042845278&partnerID=8YFLogxK
U2 - 10.1038/modpathol.3800058
DO - 10.1038/modpathol.3800058
M3 - Article
C2 - 14990969
AN - SCOPUS:3042845278
VL - 17
SP - 538
EP - 546
JO - Modern Pathology
JF - Modern Pathology
SN - 0893-3952
IS - 5
ER -