1. ¹Department of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Milan, Italy
2. ²Department of Pathology, University of Verona, Verona, Italy
3. ³Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy
4. ⁴Department of Pathology, Cannizzaro Hospital, Catania, Italy
5. ⁵Department of Pathology, Cardarelli Hospital, Neaples, Italy
6. ⁶Department of Medical Oncology, University of Verona, Verona, Italy
7. ⁷Department of Pathology, City Hospital, Verona, Italy
8. ⁸Department of Epidemiology and Statistics, European Institute of Oncology, Milan, Italy

Correspondence: Dr G Pelosi, MD, MIAC, Divisione di Anatomia Patologica e Medicina di Laboratorio, Istituto Europeo di Oncologia, Via G. Ripamonti, 435, I-20141 Milano, Italy. E-mail: giuseppe.pelosi@ieo.it

Received 13 June 2003; Revised 30 October 2003; Accepted 11 November 2003; Published online 27 February 2004.

Abstract

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.