K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung.
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.
Department of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy. giuseppe.pelosi@ieo.it
Giuseppe
G
Pelosi
Aldo
A
Scarpa
Michela
M
Manzotti
Giulia
G
Veronesi
Lorenzo
L
Spaggiari
Filippo
F
Fraggetta
Oscar
O
Nappi
Elvira
E
Benini
Felice
F
Pasini
Davide
D
Antonello
Antonio
A
Iannucci
Patrick
P
Maisonneuve
Giuseppe
G
Viale
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012907:Smoking; D016019:Survival Analysis; D014746:Vimentin / Q000032:analysis
D004273:DNA, Neoplasm; D014746:Vimentin; D007633:Keratins