Expression profiling and prediction of distant metastases in head and neck squamous cell carcinoma

¹ VU University Medical Center, Netherlands

^* To whom correspondence should be addressed. E-mail: bjm.braakhuis{at}vumc.nl.

Accepted 5 February 2006

	Abstract

Background: For breast and prostate cancer, a gene expression signature of the tumor is associated with the development of distant metastases. Regarding head and neck squamous cell carcinoma (HNSCC) the only known risk factor is the presence of three or more tumor-positive lymph nodes; approximately 50% of these patients develop distant metastases.

Aims: To evaluate whether a HNSCC gene expression signature is able to discriminate the patients with and without distant metastases. To validate the platform or chosen analysis, we included normal mucosa of the head and neck as control.

Methods: HNSCC patients in both groups had more than three tumor-positive lymph nodes and did not differ with respect to other risk factors. Statistical analysis was performed using the Student's T-test, as well as Statistical Analysis of Micro-arrays (SAM) to assess the false discovery rate for each gene. These analyses were supplemented with a newly developed method that computes deviations from Gaussian order statistics (DEGOS).

Results: In total, 2,963 genes were differently expressed between HNSCC and normal mucosa (T-test; P<0.01). More rigorous statistical analysis with SAM confirmed the differential expression of a majority of these genes. The comparison of HNSCC with and without metastases revealed 150 differently expressed genes (T-test; P<0.01), none of which, however, could be confirmed with SAM or DEGOS.

Conclusions: No evidence for a metastasis signature is found, and gene expression profiling of HNSCC has seemingly no value in determining the risk to develop distant metastases. The absence of such a signature can be understood when it is realized that for HNSCC in contrast to breast cancer, the lymph nodes are a necessary in-between station for hematogenous spread.

Key Words: expression profiling, head and neck cancer, metastasis, micro-array