Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases

In head and neck squamous cell carcinomas (HNSCC), metastasis to cervical l ymph nodes is a major determinant of patient outcome. To detect metastases, we used the MET oncogene as marker, which encodes the receptor for hepatoc yte growth factor/scatter factor, mediating epithelial cell motility and in vasiveness, The MET gene is expressed in epithelia and over-expressed in ca rcinomas of specific histotypes, but not in lymphatic tissue. A total of 15 1 lymph nodes from 20 squamous cell carcinomas were studied with both in-de pth histology and end-point and real-time quantitative RT-PCR. MET-encoded sequences were found in 61 of 151 nodes (40%), of which 24 (16%) were found metastatic by in-depth histopathology. parallel routine histopathologic an alysis of 654 lymph nodes from the same cases identified 36 metastases (5%) , Real-time quantitative RT-PCR was used to measure MET gene-specific mRNA in normal tissues, primary tumors and lymphatic metastases and showed a 2-8 -fold increased expression in tumor cells which metastasize. RT-PCR for 3 c ytokeratins expressed in HNSCC (K4, K10 and K13) proved to be less sensitiv e in detecting occult lymphatic metastases, Western blot analysis demonstra ted the presence of the full-size MET receptor in primary tumors and lymph node metastases; immunohistochemistry showed receptor localization in tumor cells. Altogether, these data demonstrate that the MET gene product is a v aluable marker with which to detect occult tumor cells in lymph nodes, than ks to its high expression in metastatic cells. After RT-PCR analysis we wer e able to attribute a move advanced stage to 10 out of 20 HNSCC cases, incl uding 5 cases classified as tumor-free after routine histopathology. (C) 20 00 Wiley-Liss, Inc.