Benign natal haemangiomatosis is characterised by the presence of multiple congenital haemangiomas restricted to the skin. It is differentiated from diffuse neonatal haemangiomatosis in which there is both cutaneous and visceral involvement, with higher morbidity and mortality.

Germline mutations in the NF2 gene are responsible for 80 p.cent of neurofibromatosis type 2 typical cases. Mutations are mainly truncating mutations or deletions, missense mutations having been reported in few cases. An important phenotypic variability is observed among gene carriers. To assess whether the phenotypic variability of neurofibromatosis 2 could be linked to genotype, clinical data of 154 patients whose NF2 germline alteration had been identified in our laboratory have been collected.

Among the primitive cardiac tumours, myxoma is the most common. This benign tumour is sometimes described in the context of Carney's syndrome, in which cardiac myxoma, cutaneous myxoma, lentigo and pigmentary nevus cutaneous lesions, endocrine disorders, and testicular, thyroid and hypophyseal tumours are associated. The cardiac myxomata observed are multiple, recurrent, and involve the four cardiac chambers, with a peak incidence at 25 years of age. These observations may exist in a familial context, linked to an autosomal dominant genetic factor, localized on the 17q2 chromosome with polymorphism of the PRKAR1a gene. As in the case of sporadic myxoma, rapid surgical treatment with cardio-pulmonary bypass is indicated, bearing in mind the increased risk of thromboembolic phenomena and sudden death from valvular encroachment. We report a case of bi-atrial myxoma observed in the context of Carney's syndrome.

Cancer affects 1 in every 500 children before the age of 14. Little is known about the etiology of this heterogeneous group of diseases despite the fact that they constitute the major cause of death by disease among this population. Because of its relatively higher prevalence, most of the work done in pediatric oncogenetics has been focused on leukemias, particularly acute lymphoblastic leukemia (ALL). Although it is now well accepted that genetic variations play a significant role in determining individual's cancer susceptibility, few studies have explored genetic susceptibility to childhood leukemia with respect to polymorphisms. The main biological mechanisms contributing to cancer susceptibility can be grouped into broad categories : (1) cellular growth and differentiation, (2) DNA replication and repair, (3) xenobiotic metabolism, (4) apoptosis, (5) oxidative stress response and (6) cell cycle. To evaluate whether candidate genes in these pathways are involved in childhood leukemogenesis, we conducted association studies. We showed that leukemogenesis in children may be associated with genetic variants and that the combination of genotypes seems to be more predictive of risk than either of them independently. These results indicate that the genetic investigation of several enzymes (or metabolic pathways) is needed to explain the physiopathology of childhood leukemia because of the complexity of the environment and that of the inter-individual variability in cancer susceptibility.

Pharmacogenomics of acute lymphoblastic leukemia (ALL) evolved rapidly in the past few years. Majority of recent findings concerns knowledge on key components of ALL treatment, 6-mercaptopurine and methotrexate. Leukemia is the most common cancer affecting children, with ALL comprising 80 % of all leukemia cases. Introduction of treatment protocols composed of several chemotherapeutic agents improved importantly survival in patients with ALL. Nevertheless, ALL is still the leading cause of cancer-related death in children. Interindividual differences in drug responses are an important cause of resistance to treatment and adverse drug reactions. Identifying pharmacogenomic determinants of drugs used in ALL treatment may allow for prospective identification of patients with suboptimal drug responses allowing for complementation of traditional treatment protocols by genotype-based drug dose adjustment.

The interest of anti-EGFR therapies has been explored very early in colorectal cancers because of a major contribution of the alterations of the pathway they initiate in colorectal carcinogenesis. Anti-EGFR monoclonal antibodies have shown their potential activity, especially cetuximab (Erbitux((R))) and recently panitumumab. The absence of response predictive factors raises some difficulties in the optimal prescription of this drug. Other anti-EGFR antibodies as well as small molecules inhibiting tyrosine kinase activity are currently explored in gastro-intestinal oncology.

Cancer chemotherapy, which followed a continuous progression all along the second half of the 20th century, is now undergoing profound changes: instead of focusing exclusively on the inhibition of cell proliferation, new developments now focus the mechanisms of oncogenesis. The name of "targeted therapy" refers to the targeting of oncogenesis. Understanding the mechanisms of oncogenesis is a requirement for the understanding of the use of targeted therapies. Each tumour follows its own natural history and characteristic oncogenic alterations, which define the potential targets for novel molecules. Prescribing targeted chemotherapy cannot be carried out without prior characterisation of the tumour, with the identification, among the various oncogenic alterations present, of the alteration to be targeted. As a consequence, it is mandatory to conceive this novel chemotherapy only on the basis of the selection of the patients who would benefit of it. This didactic review presents the general aspects of the molecular alterations of cancers, the potential targets which ensue, and the ways presently available to reach them.

Inflammatory breast carcinoma (IBC) is a rare but very aggressive tumour phenotype. Increased c-Met protein expression correlates with reduced survival and a higher metastatic risk in many human malignancies, including breast cancer Several studies have shown that c-Met protein is targetable by specific drugs. Here we compared c-Met expression in IBC (n = 41) and non IBC (n = 480). Two microarrays of IBC and non IBC tissues were constructed and standardized. C-Met, P13K and E-cadherin were immunodetected (Ven-tana Benchmark Autostainer) on serial sections. The results were quantified with an automated image analysis device (SAMBA Technologies) by immunoprecipitate densitometry of each core section (0.6 microns thick). We found that (i) c-Met is significantly overexpressed in IBC compared to non IBC (p < 0. 001), (ii) P13K is also overexpressed (p < 0.001) in IBC, suggesting that overexpressed c-Met is functionally active, at least through the PI3K signal transduction pathway ; and (iii) E-cadherin is paradoxically overexpressed in IBC. We conclude that c-Met may constitute a target for specific therapy in patients with poor-prognosis malignancies like IBC Automated image analysis of TMA is a valuable tool for high-throughput quantification of the immunohistochemical expression of the tumor proteome.

The aim of this prospective and blinded study was to investigate the diagnostic accuracy of conventional cytopathology of oral brush biopsies taken from suspicious oral lesions. In addition we checked slide based DNA image cytometry as an adjuvant diagnostic tool. Our hypothesis is that DNA aneuploidy is a sensitive and specific marker for earliest detection of oral cancer using brush biopsies. Therefore the nuclear DNA contents were measured after Feulgen re-staining using a TV image analysis system. DNA aneuploidy was assumed if abnormal DNA stemlines or cells with DNA content greater 9c were observed. Sensitivity of our cytological diagnosis in oral smears for the detection of cancer cells thus was 91.3%, specificity for the detection of non-neoplastic cells was 95.1%, positive predictive value 94.4% and negative predictive value 92.3%. The adjuvant DNA image cytometry reached a sensitivity of 97.8%, the specificity and the positive predictive value were 100% and negative predictive value was 98.1%, respectively. Smears from oral brush biopsies of all visible oral lesions are an easily practicable, cheap, minimal invasive, painless and safe screening method for detection of oral precancerous lesions and squamous cell carcinomas in all stages. We conclude that DNA image cytometry is a very sensitive and highly specific, objective and reproducible adjuvant tool for identification of neoplastic cells in oral smears.

Lung cancer is the most frequent cause of death by cancer worldwide. Despite improvements in the treatment the vital prognosis remains poor with an estimated 5-year survival rate of 15 % all stages together. Even if some environmental exposure may favour apparition of the disease, tobacco smoking is by far the greatest risk factor for developing lung cancer. Recent progresses have been made on the identification of cellular mechanisms and genetic abnormalities that make the patients more prone to develop lung cancer.

Establishing the cause of exudative pleural effusions is sometimes difficult, especially in the context of possible malignant pleural mesothelioma (MPM). Therefore, the development of new biological tools is necessary. The aim of this study was to determine the feasibility and the diagnostic contribution of genomic analysis of cells contained in pleural fluid, using DNA microarray techniques.

Sacrococcygeal teratoma is the most common and benign fetal tumor. Fetuses with sacrococcygeal tumors that are predominantly solid and highly vascularized have a high risk of fatal issue. Hydrops and tumor hemorrhage are associated with a highest risk of fetal death. Management of these tumors includes ultrasound scan with Doppler and magnetic resonance imaging (MRI) is usually used for evaluation of its intrapelvic extension and relationship to the other structures. New in-utero treatments as vascular coagulation have been applied in fetuses with highly vascular teratomas but these techniques are still experimental and need more investigations. The management of delivery depends on associated anomalies, tumor vascularity and size.