A metastatic cancer develops by accumulation of mutations in genes that control growth, survival and spreading. The latter genes have not yet been identi®ed. In lymph node metastases of head and neck squamous cell carcinomas (HNSCC), we found mutations in the MET oncogene, which encodes the tyrosine kinase receptor for Scatter Factor, a cytokine that stimulates epithelial cell motility and invasiveness during embryogenesis and tissue remodeling. We identi®ed two somatic mutations: the Y1230C, known as a MET germline mutation which predisposes to hereditary renal cell carcinoma, and the Y1235D that is novel and changes a critical tyrosine, known to regulate MET kinase activity. The mutated MET receptors are constitutively active and confer an invasive phenotype to transfected cells. Interestingly, cells carrying the MET mutations are selected during metastatic spread: transcripts of the mutant alleles are highly represented in metastases, but barely detectable in primary tumors. These data indicate that cells expressing mutant MET undergo clonal expansion during HNSCC progression and suggest that MET might be one of the long sought oncogenes controlling progression of primary cancers to metastasis. Oncogene (2000) 19, 1547 ± 1555.
Pharyngocutaneous fistula is the most common complication of total laryngectomy. The management of this problem increases hospitalization time and delays initiation of postoperative radiotherapy, where indicated. To identify factors predisposing to the development of pharyngocutaneous fistula, we reviewed the postoperative courses of 293 patients who underwent total laryngectomy at our clinic. General factors taken into account were concurrent diseases such as diabetes, liver diseases, or chronic anemia; local factors included radiotherapy before and after surgery, preoperative tracheostomy, type of cervical lymph node removal, and method of pharyngeal closure. We then compared our data with those reported in the literature by other authors. Last, we applied the Fisher exact test to a correlation we found between the higher incidence of fistula in patients with diabetes, liver diseases, or anemia. The local factor that turned out to be statistically most significant for the development of fistula was preoperative radiotherapy.
HER2/neu overexpression and its relationship with survival suggest that new therapeutic approaches targeting epidermal growth factor receptor (EGFR) family receptors could provide a new way of treating HNSCC patients with HER2/neu-positive neoplastic lesions.
Ten patients with recurrent squamous cell carcinoma of the head and neck received daily injections of interleukin-2 (IL-2) from the Jurkat T-cell line purified by high pressure liquid chromatography for 10 days. Two hundred units of IL-2 in 0.5 ml were injected 1.5 cm from the insertion of the sternocleidomastoid muscle on the mastoid. When possible, courses were repeated at 45-day intervals. IL-2 was ineffective in two patients who had already undergone functional or radical neck dissection. By contrast, in six patients with contralateral or bilateral cervical lymph nodes, complete or partial disappearance of the tumor was observed. The injections were occasionally followed by moderate local swelling and lymph node pain, but no systemic disturbances.
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