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Gene expression of lung squamous cell carcinoma reflects mode of lymph node involvement

¹ Depts of Thoracic Medicine and, ⁴ Pathology, The Prince Charles Hospital, Brisbane, ² School of Medicine, University of Queensland, and ³ Human Genetics Laboratory, Queensland Institute of Medical Research, Herston, Australia.

CORRESPONDENCE: J. E. Larsen, Dept of Thoracic Medicine, The Prince Charles Hospital, Brisbane, 4032, Australia. Fax: 61 731394957. E-mail: Jill_E_Larsen{at}health.qld.gov.au

Keywords: Expression profiling, nodal disease, nonsmall cell lung carcinoma, squamous cell

Received: December 11, 2006
Accepted March 14, 2007

Tumour, node, metastasis staging is essential for lung cancer management. However, similarly staged cancers may have markedly different prognoses, indicating that stage cannot completely explain tumour behaviour. While ipsilateral hilar node involvement is designated N1, the current authors hypothesised that primary tumours involving nodes by direct extension are biologically distinct from those involving nodes through lymphatic metastasis.

Microarrays were used to investigate the gene expression profiles of 59 primary lung squamous cell carcinomas, comparing N0 tumours (n = 35), N1 tumours by direct extension (N1d; n = 8), and N1/N2 tumours by lymphatic metastasis (N1/N2m; n = 16).

Hierarchical clustering using 125 genes differentially expressed between N0 and N1/N2m tumours found N1d tumours clustered with N0 tumours. Class prediction modelling found the expression profiles of all eight N1d tumours were more similar to N0 than to N1/N2m tumours.

The present study demonstrates for the first time that N1 tumours directly invading hilar nodes are genomically different to those that metastasise via lymphatics. Independent reports suggest that tumours with direct, rather than metastatic node involvement have better outcomes. Consequently, the data suggest that there is a need to re-evaluate the N1 staging definition in lung cancer. This is relevant for prognosis prediction and also for clinical management, particularly in selecting those patients most likely to benefit from adjuvant chemotherapy.

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