An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas


Metastasis is the process by which cancers spread to distinct sites in the body. It is the principal cause of death in individuals suffering from cancer. For some types of cancer, early detection of metastasis at lymph nodes close to the site of the primary tumor is pivotal for appropriate treatment. Because it can be difficult to detect lymph node metastases reliably, many individuals currently receive inappropriate treatment. We show here that DNA microarray gene-expression profiling can detect lymph node metastases for primary head and neck squamous cell carcinomas that arise in the oral cavity and oropharynx. The predictor, established with an 82-tumor training set, outperforms current clinical diagnosis when independently validated. The 102 predictor genes offer unique insights into the processes underlying metastasis. The results show that the metastatic state can be deciphered from the primary tumor gene-expression pattern and that treatment can be substantially improved.

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Figure 1: A predictor for HNSCC lymph node metastasis.
Figure 2: Long-term tissue storage results in loss of predictive accuracy.
Figure 3: The predictor outperforms current clinical diagnosis on the validation set.


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We thank D. van Leenen, M. Groot-Koerkamp and J. van Helvoort for microarray production and technology optimization; M. Verdaasdonk for assistance with biopsies; A. Leijen for computer assistance and J. van de Peppel for advice and discussion. Work in the group of F.C.P.H. is supported by grants from the Netherlands Organization for Scientific Research and by the European Union fifth framework project TEMBLOR.

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Correspondence to Frank C P Holstege.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Study design and procedures overview. (PDF 95 kb)

Supplementary Table 1

Clinical and histological parameters of tumors and patients. (PDF 128 kb)

Supplementary Table 2

Complete list of the 102 HNSCC predictor genes. (PDF 214 kb)

Supplementary Methods (PDF 40 kb)

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Roepman, P., Wessels, L., Kettelarij, N. et al. An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet 37, 182–186 (2005).

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