The proceedings instituted against three European patents held by the US company Myriad Genetics, on the BRCA1 gene and the breast cancer diagnosis gene, resulted in the total or partial revocation of these patents. These decisions put an end to the legal monopoly claimed by Myriad Genetics on the BRCA1 gene and on breast cancer gene tests, and left the field open to European geneticists to develop and implement their test methods within the framework of a clinical not-for-profit organization. The opposition procedure, through which any actor is allowed to challenge European patents, was used by geneticists doctors in Europe to refuse the emergence of an industrial monopoly on a medical service offered in a clinical context. The decision to revoke or strongly limit these patents was based on the European Patent Office's refusal to establish an invention priority on a sequence that had errors at the time the application was filed by the patent holder, in September 1994. The patent holder was granted an invention priority only on 24 March 1995, when it filed an application for a corrected sequence of the gene. But by then the BRCA1 gene sequence had already been divulged in a public data base, Genbank, from October 1994, notably by Myriad. Myriad Genetics' patents were thus victims of the patent race that prompted the firm to file multiple patent applications on insufficiently validated sequences, and of the conflict between diffusion in the public domain and the novelty requirement. Opposition to the patents, undertaken by a coalition of medical institutions, human genetic societies, two States, Holland and Austria, an environmental protection organization (Greenpeace), and the Swiss Labour Party, made it possible to preserve and develop the clinical economy of genetic tests in Europe. It resulted in amendments to intellectual property laws in France and thus extended the possibility of using compulsory licences for public health purposes to in vitro diagnosis.

Semaphorins, first described as axon guidance molecules, play an essential role in neural development, angiogenesis and immunological response. In 1996, two semaphorin genes, SEMA3B and SEMA3F, were isolated from chromosomal region 3p21.3 believed to contain a tumor suppressor gene based on frequent loss of heterozygosity in lung and breast cancer. Since these first studies, several semaphorins have been involved in tumor progression. Some semaphorins have been proposed to have pro-tumoral properties, whereas others have been shown to have tumor suppressive activity. This review summarizes the most recent data implicating semaphorins in cancers.

histological and clinical relationship study of 44 cases of primary cutaneous B cell lymphoma, classified according to WHO classification.

Transitional cell carcinomas of the upper urinary tract (UUT-TCCs) are rare: they account for approximately 5% of all urothelial carcinomas. 30% of patients with UUT-TCC have a history of bladder TCC, but fewer than 2% of patients with bladder TCC have UUT-TCC. Tumor microsatellite instability (MSI) is an indicator of the clonal expansion of neoplasms; it was first identified in tumors from patients with hereditary non-polyposis colorectal carcinoma (HNPCC). UUT-TCC occurs in 5% of patients with HNPCC. High-frequency microsatellite instability is present in almost 20% of cases of sporadic UUT-TCC. In cases of UUT-TCC with high-frequency MSI, hereditary cancer must be sought, especially if the patient is younger than 60 years or has a personal or family history of an HNPCC-related cancer: such patients should undergo DNA sequencing for the MSH2 gene germline mutation. Invasive UUT-TCC has a poor prognosis. 5-year survival is less than 50% for stage T2-T3 tumors and less than 10% for T4 or N+/M+ tumors. The main prognostic factors are age and tumor stage and grade. High-frequency MSI is a positive prognostic factor, especially in patients younger than 70 years with T2/T3/N0-M0 tumors.

Tuberous sclerosis complex (TSC) is an autosomal dominant inherited phakomatosis, usually diagnosed in childhood and characterized by cutaneous and neurological tumors, the latter often leading to epilepsy and mental retardation.

Breast cancer is a complex and heterogeneous disease resulting from various molecular alterations, the identification of which should have profound impact on the management of patients.

Cyclooxygenases (Cox) are prostaglandin synthetase enzymes which play a key role in mammary carcinogenesis. Several connections were demonstrated between Cox and a few oncogenes (v-src, v-Ha-ras, HER-2\neu, Wnt, p53 mutated), alimentary products (PUFAs), transcription factors (c-jun and c-fos), proapoptotic proteins [Bax et Bcl-x(L)] or antiapoptotic (Bcl-2), CYP19 aromatase gene, NFkappaB receptor (RANKL), angiogenesis (via VEGF, TXA2, oxid nitric synthetase, alphaVbeta3 integrin receptor), peroxisome gamma proliferator receptor (PPARgamma) and its ligand PGJ2 and with antitubuline chemotherapy drugs. No correlation of Cox2 expression with hormonal receptors was shown. In epidemiologic studies there is evidence of breast cancer risk reduction for women who take AINS for a lon time. Alimentary factors like resveratrol or insaturated fat acid reduce Cox2 expression in animal and could be investigated in human studies. Clinical trials are planed with the anti Cox2 celecoxib for breast cancer prevention, in adjuvant setting, in metastatic situation combined with exemestane or antitubulin drugs or in neoadjuvant therapy.

Genome wide expression analyses techniques are now applied to breast carcinoma. Several results have been achieved : molecular clustering of breast carcinomas, implementation of powerful prognostic classifications, and in some way predictive classification. Unfortunately, translation to bedside remains limited due to standardization difficulties.

As a consequence of increased screening mammography, preinvasive breast lesions represent a growing percentage of breast pathology diagnoses. Intraductal epithelial proliferations of the breast are, at present, classified into three groups: usual epithelial hyperplasia, atypical ductal hyperplasia and ductal carcinoma in situ. The boundary between those two last entities is not clearly defined on a morphological point of view although the clinical management is different. Columnar atypical lesions or flat atypical hyperplasia, frequently observed near microcalcifications, are not homogeneously managed. Lobular lesions are classified under the category of lobular neoplasia which avoid interobserver variability. Molecular biology data and immunoprofiles isolate different lobular phenotypes and link them to invasive cancer. The different systems of classifications of those different entities, the most recent molecular biology datas, controversies and consensus are described in this manuscript.

New therapeutic approaches based on the understanding of brain tumour biology are emerging. Signal transduction inhibitors (mainly targeted against the EGF receptor, the PI3K/Akt or the Ras/Raf pathways), proteases inhibitors and antiangiogenic agents are currently under investigations in clinical trials. The recent development of convection-enhanced delivery technique allows the administration of drugs which do not cross the blood-brain-barrier, such as selective toxins or immunostimulating oligonucleotides. This article reviews these emerging therapies currently under clinical trials in glioblastomas.

Several molecular genetic alterations have been characterized in gliomas in the past years. Molecular profiles have been associated with specific histologic and prognostic tumor subgroups, contributing to improve the classification of gliomas. At least two alternative molecular pathways have been suggested in the astrocytoma progression involving TP53 inactivation (secondary glioblastomas) and EGFR amplification (de novo glioblastomas) respectively. Oligodendroglial tumors have demonstrated recurrent combined loss of chromosome 1p/19q, which represent a favorable prognosis marker and probably a predictor of a good chemosensitivity of the tumor. This review discusses recent molecular advances and clinical implications with special focus on oligodendroglial tumors.

In this retrospective study, we analyse epidemiology, clinical symptoms and therapeutic results in a group of 23 children with neuroblastoma. Half of them were less than 2 years of age; in 19 of 23, the primitive tumour was abdominal; 35% of them were initially metastatic. The overall survival was 83% at 5 years and the event free survival, 75% at 5 years. Pronostic factors are age, extension of the disease at diagnosis, biologic parameters and genetic study of the neuroblast cells (amplification of N-myc oncogen). Our study shows the deleterious effect of bone lesions.