Clinicopathological significance of mitochondrial D-Loop mutations in head and neck carcinoma

Mitochondrial DNA mutations have been reported in several types of tumours, including head and neck squamous cell carcinoma (HNSCC). The noncoding region of the Displacement-Loop (D-Loop) has emerged as a mutational hotspot and we recently found that they were associated with prognosis and response to 5 fluorouracil (5FU) in colon cancers. In order to evaluate the frequence of D-Loop mutations in a large series of HNSCC and establish correlations with clinicopathologic parameters, we sequenced the D-Loop of 109 HNSCC before a treatment by neoadjuvant 5FU-cisplatin-based chemotherapy and surgery. Then, we correlated these mutations with prognosis and response to chemotherapy. A D-Loop mutation was identified in 21% of the tumors, the majority of them were located in a C-tract (D310). The prevalence of D310 mutations increased significantly with the number of cytosines in the matched normal tissue sequence (P=0.02). Hypopharyngeal cancer was significantly more frequent (P=0.03) and tobacco consumption more important (P=0.01) in the group of patients with D-Loop mutation. The presence of D-Loop mutation was not associated with prognosis or with response to neoadjuvant chemotherapy. These results suggest that D-Loop mutations should be considered as a cancer biomarker that may be useful for the early detection of HNSCC in individuals at risk of this cancer

Endoscopic cordectomy. A proposal for a classification by the Working Committee, European Laryngological Society.

The European Laryngological Society is proposing a classification of different laryngeal endoscopic cordectomies in order to ensure better definitions of post-operative results. We chose to keep the word "cordectomy" even for partial resections because it is the term most often used in the surgical literature. The classification comprises eight types of cordectomies: a subepithelial cordectomy (type I), which is resection of the epithelium; a subligamental cordectomy (type II), which is a resection of the epithelium, Reinke's space and vocal ligament; transmuscular cordectomy (type III), which proceeds through the vocalis muscle; total cordectomy (type IV); extended cordectomy, which encompasses the contralateral vocal fold and the anterior commissure (type Va); extended cordectomy, which includes the arytenoid (type Vb); extended cordectomy, which encompasses the subglottis (type Vc); and extended cordectomy, which includes the ventricle (type Vd). Indications for performing those cordectomies may vary from surgeon to surgeon. The operations are classified according to the surgical approach used and the degree of resection in order to facilitate use of the classification in daily practice. Each surgical procedure ensures that a specimen is available for histopathological examination

The Soluble Chain of Interleukin-15 Receptor: A Proinflammatory Molecule Associated with Tumor Progression in Head and Neck Cancer

International audienceInterleukin (IL)-15 is a proinflammatory cytokine, as it induces the production of inflammatory cytokines [IL-6, tumor necrosis factor alpha (TNFalpha), IL-17, etc.]. A correlation between high intratumoral IL-15 concentrations and poor clinical outcome in lung and head and neck cancer patients has been recently reported. The purpose of this study was to investigate the role of the soluble alpha chain of IL-15 receptor (sIL-15Ralpha), a natural regulator of IL-15, in head and neck cancer. Fifty-three newly diagnosed untreated head and neck cancer patients were included in this study. Quantification of sIL-15Ralpha was performed with a newly developed RIA. Increased serum sIL-15Ralpha concentrations were found in head and neck cancer patients and were closely correlated with poor clinical outcome both in terms of locoregional control and survival even on multivariate analysis. sIL-15Ralpha was mainly produced by tumor cells via proteolytic cleavage of IL-15Ralpha mediated by ADAM-17. A correlation was observed between ADAM-17 expression in tumor cells and serum sIL-15Ralpha concentrations. Surprisingly, sIL-15Ralpha did not act in vitro as an IL-15 antagonist but rather as an enhancer of IL-15-induced proinflammatory cytokines (IL-6, TNFalpha, and IL-17) that may promote tumor progression. This new tumor evasion mechanism based on amplification of the intratumoral inflammatory reaction is probably not restricted to head and neck cancer, as other tumors have been shown to release sIL-15Ralpha. Overall, these results support for the first time an original protumor role of sIL-15Ralpha in cancer