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

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 NO tumours (n=35), N1 tumours by direct extension I n=8), and N1/N2 tumours by lymphatic metastasis (M1/N2m; n=16). Hierarchical clustering using 125 genes differentially expressed between NO and N1/N2m tumours found N1d tumours clustered with NO tumours. Class prediction modelling found the expression profiles of all eight N1d tumours were more similar to NO than to N1/N2m tumours. The present study demonstrates for the first time that N1 turnours 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

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

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 NO tumours (n=35), N1 tumours by direct extension I n=8), and N1/N2 tumours by lymphatic metastasis (M1/N2m; n=16). Hierarchical clustering using 125 genes differentially expressed between NO and N1/N2m tumours found N1d tumours clustered with NO tumours. Class prediction modelling found the expression profiles of all eight N1d tumours were more similar to NO than to N1/N2m tumours. The present study demonstrates for the first time that N1 turnours 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

Profiling of molecular interactions in real time using acoustic detection

Acoustic sensors that exploit resonating quartz crystals to directly detect the binding of an analyte to a receptor are finding increasing utility in the quantification of clinically-relevant analytes. We have developed a novel acoustic detection technology, which we term Resonant Acoustic Profiling (RAP™). This technology builds on the fundamental basics of the “quartz crystal microbalance” or “QCM” with several key additional features including two- or four-channel automated sample delivery, in-line referencing and microfluidic sensor ‘cassettes’ that are pre-coated with easy-to-use surface chemistries. Example applications are described for the quantification of myoglobin concentration and its interaction kinetics, and for the ranking of enzyme-cofactor specificities. © 2006 Elsevier B.V. All rights reserved