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For many years, research has mainly been focusing on the cancerous cell and its molecular changes. However, the influence of the stroma! Micro-environment on carcinogenesis in the cancers of epithelial origin is now widely acknowledged. The micro-environment surrounding a squamous cell carcinoma of the head and neck (SCCHN) includes mainly: Cancer-associated fibroblasts (CAFs), immunity cells, and the extra-cellular matrix. Pre-clinical findings suggest that the different components of the tumoral micro-environment could modify the sensitivity of the cancerous cells to treatment. Moreover, the immunity reaction appears to influence the prognosis of solid tumors, as it has been proven in some cancers. The prognosis of the patients can be assessed-by the usual criteria such as the evaluation of the tumor (staging TNM, genetic modifications, etc.) but also by assessing the immune component of the tumoral microenvironment, using methods such as immuno-histo-chemistry through a « Immunoscore ».This clinical research commits to this will of identifying at best the different components of the tumoral micro-environment which could impact the prognosis of the epidermoid carcinomas of the oral cavity. The goal of this research is to try to determine which cells of this tumoral micro-environment appear to impact the development and the progression of the SCCHN; the main goal being to estimate the influence of the immunity and stromal cells on the prognostic of the patients. For this purpose, we first selected patients who had a SCCHN and divided them into three groups: one group with patients who didn't have a relapse within 44 months on average (between 4 and 167months) of free cancer survival, one group with patients who had a relapse locally, and one group with patients who had a relapse with metastasis away from the primary location of the tumor. These three groups were assessed by comparing the prognosis factors (age, alcohol and tobacco consumption HPV, etc.) and the intrinsic characteristics of the tumor (staging, tumoral infiltration and nodes infiltration, treatments, etc). Then, with the help of immuno-staining, we analyzed the tumors of the three groups by comparing the peri-tumoral infiltration by different inflammatory markers and of the peri-tumoral matrix: CD3 cells, CDS cells, decorin, e-cadherin and vimentin. A uni and multivariated analysis will permit us to see if these different-peri-tumoral environment markers have an influence on the different groups of patients.We will then discuss the various therapeutic possibilities that could be adjusted in terms of the tumoral micro-environment and the main technical issues it could highlight. Pendant de nombreuses années, la recherche contre le cancer s'est concentrée principalement sur les changements moléculaires au sein de la cellule cancéreuse. Récemment, l'influence de l'environnement péritumoral sur la cancérogénèse et la progression tumorale a été beaucoup étudiée, même pour les carcinomes épidermoïdes de la tête et du cou (squamous cell carcinoma of the head and neck (SCCHN)). Cet environnement a une influence majeure sur le comportement de la cellule cancéreuse et peut même induire des modifications phénotypiques de celle-ci. Ce processus est connu sous le nom transition épithéliale à mésenchymateuse ou EMT (epithelial to mesenchymal transition). Le microenvironnement se compose de différents éléments : les fibroblastes associés au cancer (CAFs), des cellules immunitaires, la matrice extracellulaire. Des données précliniques suggèrent que ces différents composants pourraient modifier la sensibilité des cellules cancéreuses au traitement. Ceci a été bien documenté pour le cancer du côlon où une relation entre l'infiltrat immunitaire intra-tumoral et le pronostic a pu être établi à l'aide d'un Immunoscore. Ceci nous amène à penser que l'environnement tumoral peut avoir une influence sur le pronostic des SCCHN. Le but de ce mémoire clinique est d'essayer de déterminer quelles cellules de l'environnement tumoral semblent influencer le pronostic des carcinomes épidermoïdes des voies aéro-digestives supérieures. Dans un souci d'uniformisation nous nous sommes concentrés sur une seule localisation à savoir la cavité buccale .Nous avons sélectionné des patients atteints d'un carcinome épidermoïde de la cavité buccale opérable, dans le but d'obtenir une starification TNM pathologique {pTNM) et d'avoir des lames des pièces chirurgicales à notre disposition. Par la suite nous avons distribué ces patients dans trois groupes : un groupe de patients sans récidive après minimum 24 mois de suivi, un groupe de patients avec une récidive locorégionale et un groupe de patients avec métastases à distance. Le temps de suivi moyen est de 45 mois (entre 4 et 167 mois). Puis ces trois groupes ont été comparés en fonction de différents facteurs pronostics connus comme la classification TNM, la rupture extra-capsulaire et la nécessité d'un traitement adjuvant. Enfin, nous avons fait des analyses anatomopathologiques des pièces de résection de ces tumeurs par des techniques d'immunohistochimie. Nous avons investigué les composantes suivantes : Infiltration par des lymphocytes par un marquage CD3 et CD8, dépôt d'une composante appartenant à la matrice extracellulaire appelé décorine, L'e-cadhérine et la vimentine afin d'explorer les phénomènes d'EMT. Une analyse, uni- puis multivariée, a été conduite afin de déterminer l'influence de ces différents marqueurs sur le pronostic des patients. Les résultats seront comparés aux données déjà existantes dans la littérature et la discussion portera sur des hypothèses de modifications de traitement, pour les patients ayant un mauvais pronostic.

Neoplasms, Squamous Cell --- Mouth --- Neoplasms, Glandular and Epithelial

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Squamous epithelia form the essential lining surface of tissues in contact with the environment, including the skin, and mucosa of the oral cavity, pharynx, larynx, esophagus, respiratory and genital tracts, and several other specialized tissues. These tissues are at highest risk for exposure to environmental carcinogens such as UV light, tobacco smoke, and infectious agents. Consequently, squamous cell carcinomas that form in these tissues are among the most common human solid tumors, and have high morbidity and mortality. The signaling pathways that regulate epithelial homeostasis and the alterations in these pathways that arise during cancer development share certain features among these different tissue sites. This book brings together timely reviews from experts in the field on mechanisms and signaling pathways such as EGFR, TGF1, NFB, PPARs and mTOR/AKT that regulate development of squamous cancer in both human and experimental mouse models, with a focus on how these specific signaling pathways can be utilized as targets for anti-cancer therapy. This comprehensive monograph will be important for researchers wishing to enter the field, for medical students, and for established basic and clinical investigators who would gain from an overview of the field.

Carcinoma, Squamous Cell. --- Signal Transduction. --- Squamous cell carcinoma. --- Skin --- Cell Physiological Processes --- Biochemical Processes --- Neoplasms, Squamous Cell --- Carcinoma --- Biochemical Phenomena --- Neoplasms, Glandular and Epithelial --- Chemical Processes --- Cell Physiological Phenomena --- Signal Transduction --- Carcinoma, Squamous Cell --- Neoplasms by Histologic Type --- Chemical Phenomena --- Phenomena and Processes --- Neoplasms --- Diseases --- Medicine --- Health & Biological Sciences --- Oncology --- Cancer --- Oncology. --- Toxicology. --- Chemicals --- SCC (Oncology) --- Squamous cell cancer --- Toxicology --- Medicine. --- Cancer research. --- Pharmacology. --- Biomedicine. --- Cancer Research. --- Pharmacology/Toxicology. --- Pharmacology --- Poisoning --- Poisons --- Tumors --- Drug effects --- Medical pharmacology --- Medical sciences --- Chemotherapy --- Drugs --- Pharmacy --- Cancer research --- Physiological effect