Pancreatic adenocarcinoma, with an incidence/death ratio of 0.99, has the worst prognosis of all cancers. Risk factors associated with the sporadic form of pancreatic adenocarcinoma are unknown and less than 10% of patients receive curative treatment (surgery associated with radiation therapy or chemotherapy) with a low 5-year survival rate (10 to 20%). In more than 90% of patients, the tumor discovered at diagnosis is not resectable or has already metastasized. Thus, a better understanding of the etiology of pancreatic cancer is essential to identify new prognostic markers and new therapeutic targets. There is a wealth of data on the identification of genetic alterations associated with pancreatic cancer and their role in its development. This review will focus on the current knowledge of genetic alterations associated with two pancreatic lesions that can potentially evolve into pancreatic adenocarcinoma, Pancreatic Intraepithelial Neoplasia (PanIN) and Intraductal Papillary Mucinous Neoplasm (IPMN). These two lesions share a large panel of typical genetic alterations which are close to those found in pancreatic adenocarcinoma. A better understanding of these alterations may lead to therapeutic targets that could help prevent the progression of PanIN and IPMN to cancer.

Organised since 1990 in France, cancer genetics has been strengthened since 2003 by the programme "Plan Cancer" which resulted in an improvement of the organisation of activities. The aim of this review is to present an update of the estimation of the needs of the population in this field for the next ten years, provided by a group of experts mandated by the French National Cancer Institute. Identification and management of major hereditary predispositions to cancer have a major impact on decrease in mortality and incidence. Sensitivity of criteria for the detection of BRCA1/2 mutations could be substantially improved by enlarging the indication for genetic testing to isolated cases of ovarian cancer occurring before 70 years and to familial cases occurring after this age limit. In the Lynch syndrome, the present criteria would have an excellent sensitivity for the detection of mutations in the mismatch repair (MMR) genes if the pre-screening of tumours on microsatellite instability (MSI) phenotype was effective, but these criteria are actually poorly applied. However, genetic testing should not be proposed to all the patients affected by tumours belonging to the spectrum of major predispositions and a fortiori to unaffected persons unless an affected relative has been identified as a carrier. The prescription of tests should continue to be strictly controlled and organised, in patients as well as in at-risk relatives. The enlargement of criteria and the improvement in the spreading of recommendations should result in an increase of genetic counselling activity and of the prescriptions of tests by a factor 2 to 4, and to a lesser extent in the clinical management of at risk persons. In a near future, it appears important to mandate experts on specific issues such as the determinants of the lack of effective application of tumour screening for MSI phenotype, the recommendations for the identification and the management of MYH-associated polyposis, or the predictive value of tumour characteristics for the identification of BRCA1/2 mutations. The expected increase in cancer genetics activity will need an optimal organisation to increase the throughput. Such measures will help in facing up to new predispositions that will probably be identified in common cancers.

Several risk estimation models for breast or ovarian cancers have been developed these last decades. All these models take into account the family history, with different levels of sophistication. Gail model was developed in 1989 taking into account the family history (0, 1 or > or = 2 affected relatives) and several environmental factors. In 1990, Claus model was the first to integrate explicit assumptions about genetic effects, assuming a single gene dominantly inherited occurring with a low frequency in the population. BRCAPRO model, posterior to the identification of BRCA1 and BRCA2, assumes a restricted transmission with only these two dominantly inherited genes. BOADICEA model adds the effect of a polygenic component to the effect of BRCA1 and BRCA2 to explain the residual clustering of breast cancer. At last, IBIS model assumes a third dominantly inherited gene to explain this residual clustering. Moreover, this model incorporates environmental factors. We applied the Claus, BRCAPRO, BOADICEA and IBIS models to four clinical situations, corresponding to more or less heavy family histories, in order to study the consistency of the risk estimates. The three more recent models (BRCAPRO, BOADICEA and IBIS) gave the closer estimations. These estimates could be useful in clinical practice in front of complex analysis of breast and/or ovarian cancers family history.

Colorectal cancer fulfils the conditions required for mass screening. Data from controlled studies indicate that it is possible to reduce colorectal cancer mortality at a population level using faecal occult blood testing. Screenings rely on biennial testing in between 50 and 74average risk subjects. Compliance must be over 50%. Colorectal cancer mortality decrease in this case between 15 and 18% in the general population, 33 and 39% among participants to screening. The European Commission, on the basis of available data recommended to organise colorectal cancer screening in the European Union. Generalisation of screening has become a reality in France. Epidemiological studies allow us to define subjects at very high risk (genetic origin) and high risk for colorectal cancer. Colonoscopy screening is recommended in first degree relatives of patients with colorectal cancer or large adenoma diagnosed before 60years or with two affected first-degree relatives, in subjects with an extended inflammatory bowel disease, or with a personal history of large bowel cancer or large adenoma. Promising research strategies are arising: immunochemical tests in the short term, stool-based DNA tests in stools and proteome-based approach in the long term.

Actually, radiation-therapy indications in non-Hodgkin's lymphoma tends to decrease in favour of exclusive chemotherapy, especially in aggressive localized diseases. In this situation, PET scan imaging would be a promising tool to identify candidates to complementary radiotherapy after initial chemotherapy. To decrease long-term morbidity, radiation doses and treated volumes should be as small as possible. New radiation technologies could contribute to reduce this risk as well. However, there are still indications for radiotherapy. Radiation therapy could be delivered with curative-intent in localized indolent non-Hodgkin's lymphoma and could be helpful in symptom relief in advanced or relapsed indolent lymphoma.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade malignancy of the skin and subcutaneous tissues that only rarely forms distant metastases. More than 90% of cases are associated with a chromosomal translocation involving the COL1A1 gene on chromosome 17 and the PDGFB gene on chromosome 22. Management of this disease is primarily surgical with excellent rates of local control obtained using either wide local excision or Mohs micrographic surgery. Data have recently shown that inhibiting platelet-derived growth factor receptors (PDGFR) with imatinib mesylate can induce high rates of clinical response in patients with unresectable or metastatic DFSP. Although wide surgical excision remains standard care, patients with locally advanced disease not suitable for surgical excision can be treated with imatinib mesylate, which sometimes allows residual DFSP to be surgically excised.

While for many years the diagnosis and therapy of colon cancer did not change drastically, recently new drugs (irinotecan and oxaliplatin, used in adjuvant or neo-adjuvant approaches) and even more recently the introduction of therapies targeting the epidermal growth factor receptor (EGFR) through the monoclonal antibodies cetuximab and panitumumab, are revolutionizing the field. The finding that only patients with a tumor with a wild type (non mutated) KRAS gene respond to anti-EGFR therapy has also affected the way pathologists address colorectal cancer. Molecular analysis of the KRAS gene has become almost a routine in a very short period of time. Pathologists will have to be prepared for a new era: from standard morphology based diagnostic procedures to the prediction of response to therapy using molecular tools.

Considerable progress was realized these last years in the understanding of the molecular mechanisms and the treatment of the GIST. Their diagnosis remains based on the morphology and immunohistochemistry. The evaluation of GIST prognosis was till know difficult to establish but a new histopronostic classification currently used allows a better therapeutic approach. The search for KIT and PDGFRA mutations is recommended to adapt a targeted therapy by KIT inhibitors. The pathologist plays a crucial role in the management of the GIST because it is on him that is based the diagnosis, the evaluation of the prognosis and the treatment (surgery and kit inhibitors).

Development and growth of odontogenic tumours depend on impairment of numerous genes and molecules. In recent years, most of the genes involved in dental development were identified. This produced a new basis for the study of oral pathology and maxillofacial carcinogenesis. A better understanding of these molecular phenomena should allow to better determine the evolution of such lesions. Research breakthroughs should facilitate the development of new molecular and genetic therapeutic perspectives.

Biphenotypic acute leukaemia (BAL) represents about 5% of adult acute leukaemia. Based on a previously described scoring system, the European Group for Immunologic Classification of Leukaemia (EGIL) proposed a set of diagnostic criteria for BAL. This scoring system is based on the number and degree of the specificity of several markers for myeloid or T/B lymphoid blasts. Here, we report the case of a BAL with Burkitt-like cytology, corresponding to "the acute lymphoblastic leukaemia, Burkitt type" L3 for the FAB classification. By flow cytometry, the blasts showed a positivity for B lymphoid cytoplasmic (CD79a and mu) and membrane (CD19, CD22, CD24, IgM) markers AND a positivity for the myeloid (CD13, CD33, CD65, CD15) markers.

Cellular morphology has a predominant place in diagnosis of hematological malignancies in spite of flow cytometry, cytogenetic and molecular biology progresses. CellaVisionDM8/96TM is automated microscope and image analysis software which are able to characterize white and red blood cells morphology and to perform platelets counts in peripheral blood smears. Validity of results is always submitted to the cytologist agreement. We routinely analyzed 99 peripheral blood smears, included 9 therapeutic cytopenias, stained with May-Grünwald-Giemsa. DM8/96TM is highly efficient in the cellular identification with great security of identity management and timesaving (30% faster than manual microscopy). Major innovations are the complete slides recording, efficiency on cytopenias processing, education functionalities and the networking ability.

Cancer Systems Biology is now accepted and recognized as a promising field both in biological and clinical research. It relies on a rigorous formalization of regulation networks into precise and unambiguous languages. It provides both detailed and modular views of the complex biological system of interest (which in cancer research is typically an interaction network governing essential cellular events such as proliferation, differentiation, cell death...) in order to facilitate the interpretation of molecular profiles of tumors. The translation of these networks into mathematical models allows prediction of the evolution of the system in time and under certain perturbations. As a result, it can not only propose specific target points for pharmaceutical purposes, but also anticipate the evolution of tumors as well as their classifications. These characteristics emphasize the important role of Systems Biology of Cancer in the future of biomedical research.