Homologies in sequence and gene organization of p53 and their relatives, p73 and p63, suggest similar biological functions. However differences exist between the p53 family members. Indeed in human tumors p53 is often mutated while p63 and p73 are very rarely mutated. In addition, in contrast to p53 which is transcribed in a unique mRNA species spanning all gene exons, each homologue expresses two types of isoforms: some with transactivation domain (TAD) showing tumor suppressive properties, the others deprived of TAD, with oncogenic properties. If p53 responds to immediate genotoxic stress, its homologues participate to the cell homeostasis of specific tissues along their development and differentiation, neuronal tissue for p73, epithelial for p63. However a collaboration between the three p53 family members has been shown to occur in response to cell genotoxic damages. Neuroblastic tumors characterized by a large spectrum of neuronal differentiation constitute a good model to study relationship between p73 and p53 as well as the regulation of their respective expression.

Glutathione S-transferases (GST), xenobiotic-metabolising enzymes, are involved in the metabolic detoxification of various environmental carcinogens. Particular genetic polymorphisms of these enzymes have been shown to influence individual susceptibility against various pathologies including cancer, cardiovascular and respiratory diseases. The results from the meta-analysis indicate that GSTM1*0 null allele was associated with enhanced risk for lung (OR (95% IC) = 1,17 (1,07-1,27)), bladder (OR = 1,44 (1,23-1,68) and larynx cancer (OR = 1,42 (1,10-1,84)). GSTT1 null genotype was associated with increased astrocytomas (OR = 2,36 (1,41-3,94)) and meningiomas (OR = 3,57 (1,82-6,92)) cancer risk. GSTP1 allelic polymorphism influence the development of bladder cancer in smokers (OR = 2,40 (1,12-4,95)) and occupational asthma (OR = 3,5 (2,7-4,6)). Finally, GSTM1*0 null allele and GSTT1*1 functional allele were associated with increased risk for coronary heart diseases in smokers (OR = 2,30 (1,40-9,00)) and OR = 2,5 (1,30-4,80), respectively). The GSTT1*1 functional allele was also significantly associated with increased risk of lower extremity arterial disease (OR = 3,60 (1,40-9,00). These epidemiological data suggest that genetic GST polymorphisms influence the individual susceptibility to these diseases. Contrary to cardiovascular disease, no evidence of interaction between GST genotype and smoking status was found in lung cancer but it has not been studied in other cancers. Consequently, other works are necessary to study the potential interaction between GST genotype and environmental carcinogens including tobacco smoke extract.

How do metastases arise from the primary tumor? To address this important question at both cognitive and clinical levels, the somatic genetic of cancers has proposed two models based on our knowledge of genes underlying tumor progression through the use of both patients' tumors and experimental models. The first model proposes the emergence of a subpopulation of rare and variant highly metastatic cells. The second model suggests the occurrence of a pre-malignant state of all the tumor cells which further metastasize without additional transitions in gene expression. Today, the science of functional genomic allows revisiting this debatted concern.

The incidence of lymphomas is high among HIV infected patients. These lymphomas are non-Hodgkin's lymphoma (NHL) in 70% of cases and Hodgkin's disease (HD) in 30% of cases. Their localization is often extra-nodal with early dissemination. B-cell high grade NHL predominates. The most frequent histological types are diffuse large B-cell lymphoma (30 to 40%) and Burkitt's lymphoma (40 to 50%). Other histological types are low-grade B-cell lymphoma, polymorphic B cell lymphoma and primary effusion lymphoma. Three main factors are predominant in HIV-related lymphomagenesis: cellular immunodeficiency, oncogene viruses (Epstein-Barr and HHV8) and molecular lesions. HIV-related cellular immunodeficiency leads to the increase of EBV infected B-cells and to the diminution of antitumor immunity. Clonal EBV genome is found in lymphoma cells in 30 to 70% of cases of HIV-related NHL. It expresses oncogenic proteins including LMP-1 which behaves like an activated CD40. It induces the expression of intra-cellular genes which stimulate cell growth and inhibit apoptosis. Cytogenetic and molecular lesions are not specific to HIV-related NHL or to histological subtypes. A better knowledge of these mechanisms should lead to the development of specific targeted treatments (antiviral, cytotoxic anti-EBV lymphocytes, cell cycle regulators).

Malignant tumours of the renal parenchyma are accompanied by extension to the inferior vena cava in 4% to 10% of cases. The objective of this study was to compare DNA ploidy and proliferation index of renal cell carcinoma (RCC) with renal vein (RV) thrombus and RCC with inferior vena cava (IVC) thrombus and to investigate a correlation between these markers and Fuhrman grade and patient survival.

To report the results of conservative surgery for the treatment of hereditary renal cell carcinoma (RCC) and to define its place with respect to new less invasive treatment options.

Systematic allelotyping of colorectal cancers and liver metastases is realized since 1996 in a close collaboration between the surgery, pathology departments and the molecular biology laboratory. Using amplification of 35 different microsatellites allelic imbalances and microsatellites instabilities were recorded. Beside the well documented increasing amount of genomic rearrangements we identified a subset of early stages tumors presenting a profile of rearrangement corresponding to high grades, and high grades cancers with a molecular profile corresponding to low grade. The comparison of synchrones liver metastases and colorectal tumors allowed us to propose for a more extensive studies the existence of sensitive structural chromosomic regions affecting separately both chromosomes and that it should be possible to identify a limited number of specific genes concerned by most of the advanced stages.

Hereditary Non-Polyposis Colon Cancer (HNPCC) or Lynch's Syndrome remains an underappreciated clinical entity-perhaps due to the restrictiveness of the diagnostic criteria. Even though HNPCC makes up only a small fraction (2-3%) of Colorectal Cancer (CRC) compared with sporadic CRC, it is important to make the diagnosis to allow for targeted management of the patients and their kindreds and thus to reduce morbidity and mortality. Better knowledge of tumor characteristics including RER phenotype may allow for the application of less restrictive diagnostic criteria; but these characteristics are not specific to HNPCC and also occur in 15% of sporadic CRC. Nevertheless, a screening strategy combining a broader clinical selection (less strict than the Amsterdam criteria) with a study of tumoral phenotype may allow the identification of more cases of HNPCC. The physician caring for cases of CRC must be aware of these screening strategies and relevant clinical and biological clues which might indicate a more complete genetic investigation.

Two thousand and three was a particularly dense year for publications and communications on therapy for colon cancer summarizing the real advance performed in this field. The last ten years allowed a rapid evolution for colon chemotherapy with a switch from 5-FU modulated by leucovorin to poly-chemotherapy (fluoropyrimidines with oxaliplatin or irinotecan) integrated into therapeutic strategies, where surgery had a place more and more important in metastatic patients. In correlation with these advances, median survival of patient with metastatic colorectal cancer is between 17 and 22 months. Targeted therapeutics with monoclonal antibody such as EGF inhibitors (cetuximab) or VEGF inhibitors (bevacizumab) had for the first time demonstrated efficacy with encouraging results in randomised trials. In adjuvant situation, LV5FU2 is less toxic than monthly FUFOL and no statistically significant difference could be detected in disease-free or overall survival between the two schedules. Oxaliplatin combined with 5 fluorouracil and leucovorin (FOLFOX4) is the first combination to demonstrate significant superiority over 5 fluorouracil and leucovorin in adjuvant treatment of colorectal cancer. Fluorouracil-based adjuvant chemotherapy benefited to patients with stage II or III colon cancer with microsatellite-stable tumours or tumour exhibiting low-frequency microsatellite instability but may be not those with tumours exhibiting high-frequency microsatellite instability (MSI). These data need to be confirmed by prospective studies before changing our therapeutic references. The number of lymph nodes analyzed for colon cancer staging is itself a prognostic variable on outcome. Laparoscopic surgery of colon cancer is demonstrated as a feasible and safe procedure. Shrinkage of tumours after administration of preoperative chemotherapy and availability of ablative techniques (radiofrequency and cryotherapy) now allow to treat with curative intent metastases initially considered as non-resectable.