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p53 gene is a member of a multigene family that includes p53, p63 and p73. The association of p73 and p63 with cell transformation has been elusive as no genetic or epigenetic alteration of these genes has been uncovered yet. Recent work has shown clearly that p73 is an essential component of the signaling pathway that lead to apoptosis after DNA damage induced by cytotoxic agents use in cancer therapy. Furthermore, it has been established that a sub-category of mutant p53 is able to interact with p73 and inhibit its apoptotic activity. Such discovery will be important for a better understanding of the signaling pathway that lead to resistance to chemotherapy., (Copyright John Libbey Eurotext 2003.)

The twentieth century has witnessed the discovery of the various genetic alterations that drive a normal cell toward neoplasia. The challenge of the near future concerns the diagnostic of these alterations and their correlation with clinical parameters such as response to therapy or survival. It will be important to define, for each patient, a specific profile of the various alterations in order to improve and personalize the therapy. It is also essential to understand the various mechanisms of these alterations in order to develop new diagnostic procedures. Furthermore, the relation between genotype and phenotype is not straightforward and can be influence by various parameters such as the localization of the mutation, the alterations of other genes or the expression of modifier genes.

The twentieth century has witnessed the discovery of the various genetic alterations that drive a normal cell toward neoplasia. One the challenge of the near future concerns the diagnostic of these alterations and their correlation with clinical parameters such as response to therapy or survival. It will be important to define, for each patient, a specific profile of the various alterations in order to improve and personalize the therapy. It is also essential to understand the various mechanisms of these alterations in order to develop new diagnostic procedures. Furthermore, the relation between genotype and phenotype is not straightforward and can be influence by various parameters such as the localization of the mutation, alterations of other genes or the expression of modifiers genes.

Introduction: Alterations of the tumor suppressor gene p53 and its protein synthesis is the most commonly observed genetic feature in human cancers. Direct diagnosis of the gene mutation using sequencing is the gold standard method. However, it requires advanced technology and is only performed in specialized research units., Current Knowledge and Key Points: Demonstration of intratumoral p53 protein accumulation using immunohistochemistry is a routine diagnostic technique. Serum detection of p53 antibodies using ELISA has been recently developed. It is an easily feasible and reproducible method for the diagnosis of p53 alterations due to self-immunization in some patients in response to intratumoral p53 protein overexpression. This phenomenon is inconstant (about one-third of the patients with a p53 gene mutation produce antibodies) and its mechanism is unclear. p53 Antibodies are found in 25% of the patients with colorectal cancer, independently of traditional tumor markers (carcinoembryonic antigen and carbohydrate antigen 19.9). The presence of these antibodies is not linked to the tumor stage. Since their ratios vary during the treatment, they might constitute a new tumor marker., Future Prospects and Projects: Early appearance of p53 serum antibodies during tumor development should make them useful for the detection of malignant transformation in patients with preneoplastic disease such as ulcerous colititis. Whether the presence of p53 antibodies in colorectal cancer patients has a prognostic significance requires further assessment.

Prostate cancer is one of the most common malignancies in men. Few authors have attempted to identify consistent genetic alterations at the molecular level in adenocarcinoma of the prostate, but those most frequently reported are loss of heterozygosity (LOH) involving chromosome arms 8p, 10q, 16q, and 18q and inactivation of the TP53 tumor suppressor gene. In order to determine if alterations frequently found in other adenocarcinomas (breast, ovarian, colorectal), including losses of genetic material from chromosome arms 1p, 3p, 7q, 8p, 11p, 17p, 17q, and 18q, are also involved in prostate cancer, we examined 20 localized early-stage prostate tumors. We detected no mutations of the TP53 gene. Allelic losses were found from 7q (33%), 8p (50%), 10q (20%), and 18q (33%). Furthermore, as the first step toward isolating tumor suppressor genes on 18q, we used six polymorphic markers and identified a small common deleted region between the chromosome 18 centromere and the D18S19 locus.

The eponym Li-Fraumeni syndrome is given to a particular form of cancer-prone family in which the main encountered tumors are sarcomas occurring in childhood and breast cancers affecting young adult females. There is also an increased frequency of cerebral tumors, leukemias and adrenal carcinomas among these families. The transmission of the cancer-proneness is autosomal dominant and related to the loss of function of the p53 tumor suppressor gene located on the short arm of the chromosome 17. The related p53 protein is identified but its precise mechanism of action and its regulation are still unclear. It seems to activate the genes which negatively regulate the multiplication of the cell and to act as a factor of transcription. A germline mutation of the p53 gene must be looked for in every cancer-prone family but also in case of multifocal tumors, particularly osteosarcomas and glioblastomas, and in case of second malignant neoplasm. This is of major scientific as well clinical interest. Indeed, the study of new families will help to better understand the molecular mechanisms underlying the syndrome. For the family itself this allow to identify the cancer prone members and to offer them preventive measures and early detection of cancers, particularly early breast cancer detection.

The p53 gene codes for a nuclear phosphoprotein which is capable of modulating the expression of certain genes implicated in the regulation of cell division. The mutation of an allele on the p53 gene with loss of the healthy allele, in different tissues such as lung, larynx, bladder, liver, skin, colon and breast, which may or may not be exposed to chemical or physical carcinogens (tobacco, radon, ultraviolet, aflatoxin B1), is associated with the occurrence of cancer. Indeed, the mutated p53 protein loses its anti-proliferative properties favouring a de-regulation of cellular multiplication with the accumulation of genetic aberrations. The homozygous deletion of the p53 gene in germ cells in the members of certain family cancers (Li-Fraumeni syndrome) leads to an increased incidence of cancers in the child or young adult. The most frequent mutations of the p53 gene end in a stabilisation of the mutated protein with immuno-histochemical nuclear marking of the cells carrying such an alteration. In certain patients this stabilisation of the mutated protein ends in auto-immunisation with anti-p53 serum antibodies. Bronchial cancer is a cancer of which the mutations of p53 are the most frequent (45-65% of bronchial cancer) as result of the mutagenic effect of tobacco smoke. These mutations seem to be associated with a bad prognosis and indeed to chemo-and radiotherapeutic resistance. The early diagnosis of p53 alterations (in dysplastic lesions or tumours which are only slightly developed) would enable new therapeutic interventions in bronchial cancer such as gene therapy or radio-immunotherapy to either restore the p53 gene to normality or to eliminate the cells expressing the mutated p53 protein respectively.

The frequency of obstructive sleep apnea syndromes in children is not negligible. The diagnosis is based on the parents' answers and on sleep recordings. Radiographs sometimes help defining the site of obstruction. However, except when there is a considerable, clinically obvious tonsillar hypertrophy (which is fortunately the most frequent case), the exact location of the obstruction may be difficult to assess. In fact, it is far less obvious and more often multiple than in adults, especially in cases of craniofacial malformation. A pharyngolaryngeal exploration technique with a flexible endoscope under general anesthesia (GA) has been developed in our department. With natural ventilation, when a GA is induced with halothane through a mask, muscular relaxation similar to that of natural sleep is obtained. A thin flexible endoscope is then inserted through the mask to observe the obstructive structures at the nasal, rhino/oropharyngeal or pharyngolaryngeal levels. During the past two years, 17 children were examined with this technique, which allows an extremely accurate diagnosis of the site of the obstruction. Four children had a craniofacial malformation. The examination evidenced 9 cases of adenotonsillar hypertrophy, 4 cases of dynamic laryngeal obstruction, 3 cases of basilingual obstruction and one case of circular collapse of the oropharynx. The evolution under treatment confirm the merits of this endoscopic examination technique for the etiological diagnosis of respiratory obstruction.

Surgical orbital decompression in 5 patients with basedowian optic neuropathy restored the visual acuity and visual field in all cases. The place of surgery among the different therapeutic options proposed for this serious complication of Basedow's disease is discussed, as well as the advantages over other decompression techniques of the procedure used : the cutaneous approach to a trans-ethmoidonasal decompression.