Colorectal cancer affects over 500,000 individuals yearly. Much of the benefit of colorectal cancer screening has been attributed to detection and removal of adenomatous polyps, highlighting the importance of colorectal polyps as targets for intervention and as biomarkers for colorectal cancer risk. Positive familial history (first or second degree relative) for colorectal carcinoma can be found in approximately 30% of all newly diagnosed cases, but less than 5% will be due to a defined genetic category of hereditary CRC. Genome-wide association studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer. The risks conferred by the susceptibility alleles are low. 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.

Cancerogenesis is initiated by DNA instability that induces modifications in stem cells. Regulation is organ specific and depends on morphogenetic factors. DNA instability is alternatively related to chromosomal aberrations or DNA replication errors. Chromosomal instability is the most frequent characteristics of colon adenocarcinoma, and is observed in distant metastatic foci. It is associated with somatic APC mutations that deregulates the WNT pathway. Position of the mutations within the coding sequence are essential for the cell migration capacities thus for stem cell metastasis ability. After this step the new morphogenic program is able induce expansion in the host organ.

The proteasome plays a pivotal role in the turnover of regulatory transduction proteins induced by activated cell membrane growth factor receptors. The epidermal growth factor receptor (EGFR) pathway is crucial in the development and progression of human epithelial cancers. The combined treatment with EGFR inhibitors has a synergistic growth inhibitory and pro-apoptotic activity in different human cancer cells which possess a functional EGFR-dependent autocrine growth pathway through to a more efficient and sustained inhibition of Akt. But resistance has been observed in case of KRAS mutation. Inhibition of a single transduction pathway is often inefficient due to activation of alternative signalling. The mammalian target of rapamycin (mTOR) is a key intracellular kinase integrating proliferation, survival and angiogenic pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR blockade is pursued to interfere at multiple levels with tumour growth. Targeting mTOR pathway overcomes resistance to EGFR inhibitors and produces a cooperative effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested in a clinical setting.

Medullary carcinoma and serrated adenocarcinoma are two variants of colon cancer which are associated to particular pathways. Medullary carcinoma is invariably associated with MSI while serrated adenocarcinoma is characterized by excess of methylation. TNM classification and the tumoral grade are still the most important prognostic factors. Several parameters including morphological criteria, molecular features or immunohistochemical markers seem to be relevant but none of them are today used in clinical practice. A more accurate approach of the evaluation of these additional parameters should improve their prognosis values. double dagger.

Soft-tissue sarcoma is a heterogeneous group of diseases. Prognostic factors for local recurrence, metastatic recurrence, and overall survival are different and optimal treatment strategies need to take them into account.

Even if prognosis of epithelial ovarian cancer remains very bad, survival and response to treatment are variable according to the patients. Determination of new prognostic markers helps us to adapt therapeutics for each patient and is necessary for the elaboration and the interpretation of clinical research studies. Many prognostic factors related to the tumor, the patient or the treatment, have been evaluated. The goal of this work is to review these parameters. So far, the most powerful variables are volume of residual disease after cytoreductive surgery, FIGO tumor stage, histologic type and grade of differentiation. The progress and accessibility to novel technologies applied to biology will make possible in the future the assessment of new prognostic profiles-based on genetic and/or proteomic tumor characteristics. The future also relies on the identification of predictive factors of response to treatment, but force is to note that on the last hundred publications testing predictive factors (p53, HER2, Topo-2-alpha, BRCA...), none have modified today our clinical practices.

For many years, 5-fluorouracil was the unique drug approved in the management of colorectal cancer. In the last decade, oxaliplatin, irinotecan, capecitabine and more recently targeted therapies as cetuximab and bevacizumab have been added to chemotherapy schedules. Prognosis and predictive factors are deeply needed to improve the management of the patients. To date, the TNM classification remains the only factor widely approved. But thanks to the progress of fundamental and translational research, it appears clearly that more clinical and molecular markers should be available soon to help the physician in the management of colorectal cancer.

Cholangiocarcinoma represents the second most common primary hepatobiliary cancer. Although few patients are candidates for surgery, surgical resection represents the only potential curative option. The prognosis for patients remains poor, despite advances in the understanding of mechanisms involved in carcinogenesis. This review aims to assess clinicopathological factors and biological markers for the ability to predict prognosis. Clinicopathologic factors most often cited are tumor size, lymph node involvement, resecability and surgical margins involvement. Molecular biomarkers have been examined and a number of these, including mdm2, p27, matrix metalloproteinases and vitamin D receptor appear to have prognostic utility. The advent of 'omic'-based profiling offers the potential to assess many different biomarkers at the same time. This 'protein/gene signature' could open the way for developing valid and reproducible predictors of survival based on protein or gene profiles.

Malignant gliomas are the most prevalent type of primary brain tumor in adults. They are classified into astrocytomes, oligodendrogliomes and oligo-astrocytomes on the presumed cell of origin. They are then classified according to their degree of malignancy into low-grade gliomas (I and II) and high-grade gliomas (III an IV) according to WHO classification. Conventional therapy includes surgery, radiotherapy and chemotherapy and is mostly palliative. Because patients with a same histologic diagnosis have variable outcomes, there is a need to develop better prognostic markers to predict tumor behaviour and response to therapy. For patients with low-grade gliomas, several clinical parameters affect prognosis and therapeutic options: histological type, tumor measurements, young age, performance status. Prognostic scores have been established based on a combination of these different clinical factors. For high-grade tumors, prognostic and predictive molecular markers have been identified. The combined loss of 1p and 19q is strongly correlated with the oligodendroglial phenotype and is associated with both chemotherapeutic response and prolonged overall survival in anaplastic (grade III) oligodendrogliomas treated with PCV chemotherapy and probably with temozolomide. Many glioblastomas have dysregulated epidermal growth factor receptor and among them, the co-expression of the mutant receptor subtype EGFRvIII. The clinical significance of these EGFR alterations is still debated. Nevertheless, co-expression of EGFRvIII and PTEN seem to be predictive factor of response to EGFR inhibitors currently tested in glioblastomas. In addition, the MGMT-methylation status is an independent predictor for glioblastoma patients treated with an alkylating agent: the epigenetic inactivation of the DNA repair gene MGMT is associated with a better response to chemotherapy and a better outcome. This status may have important implications for the design of future trials.

The thyroglossal duct cyst (TDC) is a frequent pathology in head and neck surgery whose diagnosis and treatment are well known. Hereditary forms are very rare. In a case report, the author describes the familial cases in the international literature and discusses the genetic inheritance patterns.

The aim of this work was to study the correlation between the mitochondrial microsatellite, situated between the nucleotides 303 and 315 of the mitochondrial genome and the breast cancer in Tunisia.

Neoadjuvant chemoradiotherapy is considered at the present time as the standard treatment of most T3-4 rectal cancer. In France a combination of radiotherapy (45 Gy/5 weeks) with concurrent capecitabine (1,600 mg/m2) is the most popular protocol. Randomized trials try to optimize this approach using new cytotoxic drugs and/or radiation dose-escalation. The introduction of biotargeted therapies (anti-EGFR or antiangiogenic) is an attractive field especially selecting the treatment according to K-ras mutation. For T2 and 'early T3' present studies are using neoadjuvant chemoradiation followed by transanal local excision in case of good tumor response. In frail elderly patients, a new trend is to use mainly exclusive irradiation to control the tumor and avoid the excessive toxicity of open surgery in this group of patients. As rectal cancer is presenting many different clinical situations, an individualised treatment appears justified.

Most adrenocortical tumors are benign; adrenocortical carcinomas are rare but their prognosis is poor and their therapeutic is sparse. In most adrenocortical tumors, the morphological approach brings sufficient elements to establish the differential diagnosis between a benign and a malignant tumor but in few cases, it is insufficient. Moreover, morphology is limited for predicting prognosis of adrenocortical carcinomas. These observations led to development of other approaches, in particular genetic approaches. These genetics findings already have repercussions for the patients in the development of molecular markers for diagnosis and prognosis and in the future they could help in the development of new morphological approaches, in particular immunohistochemical approaches.

Fifteen START domain-containing proteins exist in mammals. On the basis of their structural homology, this family is divided into several sub-families consisting mainly of non-vesicular intracellular lipid carriers. With the exception of the Thioesterase-START subfamily, the other subfamilies are represented among invertebrates. The START domain is always located in the C-terminus of the protein. It is a module of about 210 residues that binds lipids, including sterols. Cholesterol, 25-hydroxycholesterol, phosphatidylcholine, phosphatidylethanolamine and ceramides are ligands for STARD1/STARD3-6, STARD5, STARD2/STARD10, STARD10 and STARD11, respectively. The lipids or sterols bound by the remaining 7 START proteins are unknown. The START domain can be regarded as a lipid-exchange and/or a lipid-sensing domain. The START domain consists in a deep lipid-binding pocket--that shields the hydrophic ligand from the external aqueous environment--covered by a lid formed by a C-terminal alpha helix. Within the same subgroup, such as the sterols-carriers subgroup, different START domains have similar biochemical properties; however, their expression profile and their subcellular localization distinguish them and are critical for their different biological functions. START proteins act in a variety of distinct physiological processes, such as lipid transfer between intracellular compartments, lipid metabolism and modulation of signaling events. Mutation or misexpression of START proteins is linked to pathological processes, including genetic disorders, autoimmune diseases and cancers.