1. ¹Clinical Pharmacology and New Drug Development Unit, European Institute of Oncology, Milan, Italy
2. ²Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy
3. ³Department of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy
4. ⁴Division of Pathology and Laboratory Medicine, European Institute of Oncology, Milan, Italy
5. ⁵Thoracic Surgery Division, European Institute of Oncology, Milan, Italy
6. ⁶School of Medicine, University of Milan, Milan, Italy

Correspondence: Dr F Toffalorio, Clinical Pharmacology and New Drug Development Unit, European Institute of Oncology, Via Ripamonti, 435, Milan 20141, Italy. E-mail: francesca.toffalorio@ieo.it

⁷These authors contributed equally to this work.

Received 19 December 2008; Revised 21 August 2009; Accepted 24 September 2009; Published online 10 November 2009.

Abstract

The aim of this study was to investigate the influence of histology and site of analysis (primary tumor versus lymph node) on the expression of genes involved in gemcitabine and cisplatin activity in non-small-cell lung cancer (NSCLC). Excision repair cross-complementing-1 (ERCC1), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-NT), cytidine deaminase (CDA) and ribonucleotide-reductase regulatory subunits (RRM1 and RRM2) were analyzed by quantitative-reverse transcription-PCR in 88 microdissected samples from 69 chemonaive patients. The results showed different patterns of expression for all studied genes, suggesting a possible stratification of the patients. No difference was observed between primary tumor and lymph node metastasis, as well as in adenocarcinoma and squamous-cell carcinoma specimens, while we found a correlation between the CDA-A79C polymorphism and gene expression levels. These data suggest a similar genetic susceptibility to gemcitabine–cisplatin regimens for squamous cell and adenocarcinoma and support the use of both lymph node and primary tumor for the expression profiling of NSCLC.