The study of the clinical, histological and immunohistochemical aspects of three kidney tumors corresponding to synovial sarcomas operated on in our center over three years.

Cancer prevention has to be based on robust biological and epidemiological data, therefore its reappraisal becomes mandatory in view of recent progress in the understanding of carcinogenesis. The first phase of the carcinogenic process, that of initiation, is generally associated with mutation; however the role of extrinsic mutagens is less critical than was thought two decades ago. During intracellular oxygen metabolism, reactive oxygen species (ROS) are made which are potent mutagens. Defense mechanisms against these intrinsic mutagens include scavenger and enzymatic systems which destroy them (catalase, superoxide dismutase). When the radiation dose is low, DNA repair is very effective as well as the elimination of cells with unrepaired or misrepaired DNA. Therefore a small increase in the number of ROS, such as that caused by a small dose of radiation has most probably no significant effect on the risk of DNA damage. These conclusions are consistent with the concept of a practical threshold. The second phase, that of promotion, appears to be the key one. During the promotion phase, initiated cells must acquire new properties (immortalization, release of angiogenic factors, resistance to hypoxia, etc.) in order to become precancerous. This evolution is due to the accumulation in the genome of 6 to 10 new alteration defects. In the clone of initiated cells, the occurrence in one cell of a mutation or an epigenetic event gives birth to a subclone. There is a Darwinian type competition between the subclones and those with the more rapid growth because dominant (the acceleration of the growth rate can be due to shorter cell cycles or to an alleviation of cell proliferation exerted by the neighboring cells or the microenvironment). In the dominant subclones new genomic events provoke the appearance of new subclones growing more rapidly and having greater autonomy. The process is very slow because the specific genetic events that favour this evolution seldom occur. Promoting factors are agents that either perturb intercellular signalling or stimulate cell proliferation (e.g. hormones) or increase cell mortality: mechanical or chemical irritation (e.g. alcohol, bacteria, viruses) thereby inducing compensatory cell proliferation. Thus, gradually precancerous cells become able to divide more rapidly with greater autonomy. This phase ends when a subclone of cells has acquired the capacity of autonomous proliferation. The third phase is that of progression during which cells proliferate regularly without any stimulation. In one of the cells of one of the precancerous lesions (e.g. polyps) a cell acquires the capacity of invading surrounding tissue or to metastasize. The whole carcinogenic process is very slow, extending over several decades, because the specific mutations seldom occur and the probability of an accumulation of several specific mutations in the same cell or cell lineage is very small. It can be accelerated by intense stimulation of cell proliferation or genetic instability. Ionizing radiations act firstly as a mutagen, however when the dose is high they also kill a significant proportion of cells and by a homeostatic mechanism they induce cell proliferation and clonal amplification. It has been claimed that even the smallest dose of radiation can induce a cancer. This concept is associated with the LNT model and it is not based on scientific evidence. It has fuelled a fear of radiation which had detrimental consequences. Conversely the high efficacy of defense mechanisms against radiocarcinogenesis, particularly when the tissue is not disorganized, can explain the lack of carcinogenic effect of contamination by small doses of radium or thorium which has been observed on radium dial painters or in patients injected with thorotrast. The study of second cancers in patients treated by radiotherapy could provide important information and should be actively pursued with two aims: reduce the incidence of second cancers; to better understand radiocarcinogenesis and the relation between dose and carcinogenic effect.

The surgeon must know the importance of angiogenesis in wound healing. He must also use anti-angiogenics to change the clinical situations and make curative a potentially ineffective surgery. However, these strategies require daily biological indicators able to quantify the tissue activity, that we do not possess yet, nor have we any indicator to predict tumour sensitivity to anti-angiogenics.

VEGF represents a model of gene expression regulation. RAS/RAF/MEK/ERK and PI3 Kinase pathways, activated in response to growth factors stimulation or by oncogenes, contribute to its expression by activating transcription factors or inactivating proteins implicated in degradation of its mRNA. These factors (Sp1/Sp3, HIF-1 and TTP) constitute molecular markers of tumor aggressiveness. VEGF is overexpressed in solid or hematologic tumors. Thus, numerous compounds regulating angiogenesis by targeting VEGF have been developed. However, their effects are not as spectacular as expected. The existence of anti-angiogenic isoforms of VEGF could be a cause of their less potent activity. These different points are discussed in this review article.

Micro RNAs (miRNAs) are small non-coding RNAs that regulate gene expression. Many studies show that they are implicated in essential physiological functions and particularly in tumors. Specific alterations of miRNA expression have been identified directly involved in carcinogenesis. Indeed, miRNAs could act as oncogenes or tumor suppressors. In addition, some miRNAs deregulations seem to be associated to specific tumors subtypes, suggesting that they could be used as tumor biomarkers. In this review, we summarize recent works about miRNAs and hepatocellular tumorigenesis in order to understand the role of these small non-coding RNAs in the carcino-genesis process and their possible use as diagnostic and prognostic markers of these tumors.

Detection and diagnosis of prostate cancer has challenged researchers and clinicians for several years, particularly with the increase of its incidence. With the advent of optimal treatments for each patient, diagnosis and prognostic tools arouse more and more interest. Effectively, it becomes necessary to assess even better the aggressiveness of the tumour in order to choose the most appropriate treatment and, thus to make a correlation between the phenotype and the genotype. The biological screening relies on PSA alone currently but should know another era soon with the advent of new markers, such as urinary gene PCA3, usefull for patients with previous negative biopsies. The techniques of biopsies and medical imaging are also going through multiple changes and evolutions that are about to increase their reliability. The optimization of MRI allows more precise diagnosis of local invasion and is usefull to optimize. Finally, the emergence of biological prognostic markers, such as endothelin or semaphorin 3A, whose expressions differ according to the type of cancer, should help to predict disease's gravity and outcome. The comprehension and the understanding of carcinogenesis pathways leads to new perspectives for targeted and earlier cancer therapies.

Two main approaches are generally used to study the epidemiology of primary brain tumors. The first approach is to identify risk factors, which may be intrinsic or related to external causes. The second main approach is descriptive. Intrinsic factors potentially affecting risk include genetic predisposition and susceptibility, gender, race, birth weight and allergy. Radiation exposure is the main extrinsic factor affecting risk. A large body of work devoted, among others, to electromagnetic fields and especially cellular phones, substitutive hormonal therapy, pesticides, and diet have been published. To date, results have been discordant. Descriptive epidemiological studies have reported an increasing annual incidence of primary brain tumors in industrialized countries. The main reasons are the increasing age of the population and better access to diagnostic imaging. Comparing incidences from one registry to another is difficult. Spatial and temporal variations constitute one explanation and evolutions in coding methods another. In all registries, weak incidence of primary brain tumors constitute a very important limiting factor. Renewed interest from the neuro-oncological community is needed to obtain pertinent and essential data which could facilitate improved knowledge on this topic.

For over 40 years, four therapeutic modalities, namely surgery, radiotherapy, chemotherapy and hormone therapy have formed the core of anticancer treatments. Their mode of action is thought to involve a direct cytotoxic action on tumor cells. Recently, the discovery of tumor-associated immunosuppression and tumor immunosurveillance has led to cancer being reconsidered not only as an organ disease but also as a host disease. This new concept is supported by the recent discovery of the immunogenic effects of tumor cell death induced by a variety of cytotoxic drugs. This work describes a new pathway of tumor-derived antigen presentation mediated by the alarmin HMGB1 (released by dying tumor cells in response to chemo/radiotherapy) and by TLR4 on dendritic cells. In this model, TLR4 recognizes? tumor-derived antigens, leading to T cell activation and to the induction of an antitumor immune response. Accordingly, we show that breast cancer patients bearing a loss-of-function mutation of the TLR4 receptor have shorter disease-free survival, confirming the major role of the immune system in the response to cytotoxic treatments. The response to chemotherapy and/or radiotherapy may thus combine both direct cytotoxic effects and the development of long-term antitumor immunity. We anticipate that these new results will have major impact on cancer management.

Mast cell disorders are defined by the accumulation of mast cells in one or more organ systems. Cutaneous forms are mainly observed in children whereas systemic forms are predominant in adults. Mast cells cause symptoms by the release of proinflammatory mediators or by infiltration of various organs. The measurement of serum tryptase has opened the possibility of screening for mastocytosis, which must be taken into consideration in case of severe anaphylactic reactions. Definite diagnosis is established based on a biopsy of skin or bone marrow. An activating mutation of stem cell factor receptor c-kit is often found. Treatment is based on control of the symptoms triggered by mast cell degranulation. Moreover, novel treatment options targeting mast cell proliferation become available for clinical use.

Primary hyperparathyroidism is frequent. Most new cases are diagnosed in post-menopausal women, and are mildly progressive. Surgery is imperative for patients under 50, for symptomatic patients, especially with osteoporosis. Familial hyperparathyroidism can be related to mutations of the menin (MEN1), Ret (MEN2), HRPT 1 and 2 genes or calcium sensor, and have different management, work-up and prognosis.

Soft tissue tumors account for approximately 25% of neonatal tumors and are most often benign (more than 2/3 of cases). Vascular tumors are the most frequent benign tumors and infantile hemangioma accounts for 32% of these tumors, affecting 1 out of 200 children at birth. Kaposiform hemangioendothelioma (KH) is a rare vascular tumor with locally aggressive behavior. More than 50% of KH are associated with the Kasabach-Merritt phenomenon, a condition characterized by thrombocytopenia and consumptive coagulopathy. Malignant soft tissue tumors are, after neuroblastoma, the second cause of cancer in neonates. Infantile fibrosarcoma (IF) is a rare tumor that most often affects the extremities of children aged 4 years or younger. A recurrent t(12;15) (p13;q25) rearrangement fusing the ETV6 gene with the NTRK3 neurotrophin-3 receptor gene has been identified in IF. Complete conservative surgical resection is usually curative. Chemotherapy is indicated when initial surgical removal cannot be accomplished without unacceptable morbidity. Prognosis of IF is excellent, with reported overall survival rates ranging from 80 to 100%. Neonatal rhabdomyosarcoma (RMS) is a rare tumor (0.5-1% of RMS). The primary tumor predominantly involves the limbs and the genitourinary tract. Treatment is based on age-adapted chemotherapy and surgery. Prognosis of RMS in children less than 1 year old appears to be comparable with that of older children.

Extra-abdominal fibromatosis is an uncommon benign breast lesion resembling an infiltrative carcinoma in its clinical and radiological presentation. Surgical excision with wide margins remains the treatment of choice to avoid recurrence of this locally aggressive tumor. We present a case in which surgical biopsy allowed the diagnosis of a breast fibromatosis and we discuss its clinical, diagnostic, pathological and therapeutic particularities.

The genome-wide association approach has been the most powerful and efficient study design thus far in identifying genetic variants that are associated with complex human diseases. This approach became feasible as the result of several key advancements in genetic knowledge, genotyping technologies, statistical analysis algorithms and the availability of large collections of cases and controls. With all these necessary tools in hand, many genome-wide association studies were recently completed, and many more studies which will explore the genetic basis of various complex diseases and quantitative traits are soon to come. The recent large genotyping studies have identified a new repertoire of cancer susceptibility genes and loci which are characterized by common risk alleles. Many of these loci were detected at low power, indicating that many further loci will probably be detected with larger studies. For the most part, the loci were not previously suspected to be related to carcinogenesis, and point to new disease mechanisms. The risks conferred by the susceptibility alleles are low, generally 1.3-fold or less. The combined effects may, however, be sufficiently large to be useful for risk prediction, and targeted screening and prevention, particularly as more loci are identified.