Pituitary adenomas are common brain tumours at autopsy and radiological series of unselected population. Historically, few epidemiologic data regarding the prevalence of clinically apparent pituitary adenomas have been available. Recently, a cross-sectional study conducted in Liège, Belgium, noted that clinically-apparent pituitary adenomas occurred with a prevalence of 1:1064 inhabitants, which is 3.5-5 times the previously reported prevalence. Pituitary adenomas occur predominantly as sporadic tumors, but also in a familial setting or associated to some familial/isolated tumoral syndromes. The recent characterization of the novel clinical entity FIPA (Familial Isolated Pituitary Adenomas) increased the prevalence of familial pituitary adenomas which account now for about 5% of pituitary tumors. Distinct genetic mechanisms are continuously identified and increase our understanding of the complex clinical presentation and sometimes unpredictable evolution of pituitary adenomas.

Bladder cancer mainly affects patients aged 50 years or more and requires close and repeated surveillance. Flexible cystoscopy associated with urinary cytology are the currently recommended diagnostic and follow-up methods. Because medical imaging techniques remain rather unsatisfying for bladder carcinoma detection, research efforts have focused on urinary markers of the disease. Various approaches were tested with results generally too unconsistant to replace cystoscopy. Recently, the department of Urology at the University of Liège together with the Biotechnology Company OncoMethylome Sciences have been interested in testing whether the detection of hypermethylated genes in voided urine samples would be of value for the detection of bladder cancer. The method is based on the Methylation-Specific PCR technology (MSP). This approach has the theoretical advantage of being non invasive, reproducible and based on DNA, whose stability, in urine, is higher than that of proteins. The results of a large prospective study, recently publised in European Urology, have shown that the identification by MSP of 2 methylated genes, TWIST1 and NID2, in voided urine samples, is a sensitive (+/- 90%) and specific (+/- 93%) test for the detection of bladder cancer. The test is largely more sensitive than cytology while both techniques have similar specificity. Based on these promising results, we are currently evaluating this novel, non invasive MSP approach for the follow-up of patients with non-muscle invasive bladder cancer.

Rhabdoid tumours are rare aggressive tumours of infancy. The definition classically relies on a characteristic morphology and the inactivation of the hSNF5/INI1 tumour suppressor gene. This entity includes central nervous system tumours (ATRT), renal tumours (RTK) and soft-part tumours. Their rarity and morphological pleomorphism make the diagnosis often challenging. However, the recently introduced immunohistochemistry with anti-INI1 (anti-SMARCB1) antibody is a very useful diagnostic tool. Deletions at the 22q11.2 locus and mutations in hSNF5/INI1 sequence must be investigated in order to confirm the diagnosis and to give insights on a presumable germline mutation. Indeed, a predisposition may be found in up to 30% of cases. The treatment is based on aggressive chemotherapy, surgery and irradiation. The prognosis remains poor and the survival rate is below 30%, whatever the anatomic location. Understanding the role of hSNF5/INI1 within the SWI-SNF complex for the epigenetic regulation of transcription might drive the future targeted therapies.

Ten years after the use of alpha interferon in chronic myelogenous (CML) leukaemia treatment, we review this treatment.

Interest for development of molecular biomarkers tends to increase in clinical management of lung cancer. Indeed implementation in clinics of new molecules targeting epithelial growth factor (EGFR) such as erlotinib or gefitinib, rise several questions regarding the potential value of EGFR and KRAS mutations to predict therapeutic response. In the current review, we discuss the utilization of such biomarkers regarding published clinical data and the possibilities versus limitations associated with analyses performed in molecular laboratory on a daily setting basis.

KRAS mutations are currently the most frequently mutated oncogenes in non-small cell lung cancers (NSCLC). A growing body of evidence suggests that targeting RAS could be an efficient strategy in NSCLC. Several approaches have been developed to target either RAS protein or downstream effectors such as RAF or MEK. First clinical trials evaluating farnesyltransferases inhibitors have led to unsuccessful results. However, targeting RAF and MEK could be a more efficient approach in NSCLC.

The KRAS protein is known to play a key role in various oncogenic pathways. KRAS mutations are found in 20-30 % of patients with non-small cell lung cancer (NSCLC). The majority of mutations are found at KRAS codons 12 and 13, and they appear to be more frequent in smokers and adenocarcinoma. The mutated protein is in its active state despite absence of stimulation, which leads to the constitutive activation of downstream pathways responsible for cellular disorder. The identification of new biomarkers to predict the evolution of cancer pathogenesis (predictive factor) and the sensibility to treatments (predictive factor) is one of the major objectives in oncology research. KRAS mutations are a potential candidate biomarker and numerous studies have tried to confirm its place as a prognostic/predictive biomarker in NSCLC. The results are contradictory and most studies are retrospective. The first results of prospective studies are currently reported, in particular with the use of antibodies against EGFR. The exact place of KRAS in medical thoracic oncology remains to be determined and further studies are needed. To date, KRAS mutations are not a biomarker to be used routinely.

Targeted therapy against the EGF receptor was shown to be effective in a subgroup of patients with KRAS wild-type colorectal cancer. Therefore, cetuximab (Erbitux) or panitumumab (Vectibix) obtained the authorization by the EMEA restricted to patients with KRAS wild-type tumours. KRAS mutational testing has become part of the standard care in patients treated with EGFR targeting therapy. Testing for KRAS mutations is not standardized, there is a multitude of methods, some of which are commercially available CE marked techniques. Most frequently used assays are developed in this review. It is very difficult today to tell which test is the most reliable. Moreover tumour samples are very heterogeneous (fixation, biopsy, surgical specimen, neoadjuvant treatment) and one "best" method could depend upon the type of sample. A STIC program is on going in France (MOKAECM) to initiate a quality assurance (QA)-program for KRAS testing. All INCa labelled laboratories that develop somatic oncology genetic tests participate to this program. Methods will be tested on cell line DNAs at first, then DNAs from paraffin embedded tumours will be shared and typed by the various laboratories. Finally, an economical evaluation will be done to compare techniques at all levels. This is of importance since KRAS testing needs to be done in a wide numbers of laboratories with similar value. KRAS testing is the first predictive genetic test in a frequent solid tumour, the establishment of a QA-program can serve as a future example for the introduction of other markers based on tumour genetic alterations.

Colorectal cancer remains a leading cause of cancer deaths. Over the last decade, many new drugs have emerged in the treatment of metastatic colorectal cancers. Thus, significant progress has been achieved with daily use of oxaliplatin, irinotecan, or similar oral 5-fluorouracil (capecitabine or UFT). The identification of new molecular targets has allowed the development of new antitumor agents directed against receptors for growth factor or cons key factors involved in the process of angiogenesis. Large randomized trials of metastatic colorectal cancer have demonstrated significant clinical benefit with bevacizumab (inhibiting the vascular endothelial growth factor VEGF) and inhibitors of epidermal growth factor receptor (EGFR), namely cetuximab and the panitumumab. In this article, we review the role and impact of mutational status of KRAS in the care of patients with colorectal cancer metastasis.

Cetuximab and panitumumab are anti-EGF receptor antibodies, used in the treatment of colorectal cancer. Phase I and II studies have shown an interest in these molecules, after failure of chemotherapy combining 5-fluorouracil, folinic acid and oxaliplatin (Folfox) or irinotécan (IFL and Folfiri). Cetuximab with irinotécan has been approved by regulatory authorities following the results of a randomized phase II study where the combination arm (cetuximab-irinotécan) was superior to cetuximab alone. Retrospective studies have highlighted the impact of KRAS mutational status in the efficacy of EGFR antibodies. KRAS mutation is associated with a lack of response. Subgroup analysis of prospective studies have confirmed these hypothesis in first and second line metastatic treatment in combination with chemotherapy and in third line in monotherapy. At present cetuximab is approved in combination with chemotherapy in patients with non mutated KRAS metastatic colorectal cancer while panitumumab is only approved in monotherapy after failure of conventional chemotherapy.

The management of patients with advanced or localized colorectal cancer (CRC) remains to date exclusively based on clinical, radiological and pathologic data. In CCR, KRAS mutations are detected in approximately 30-40% of tumours. In patients with a localized CRC, the prognostic role of KRAS mutation is not yet demonstrated with contradictory results in literature. For patients with metastatic CCR, KRAS mutations are a prognosis value for patients treated by anti-EGFR antibody. Indeed, despite the use of monoclonal antibodies against epidermal growth factor receptor (EGFR) in metastatic CRC, the detection of molecular alterations in tumours is not integrated in the routine practice for patient decision-making. In patients treated with anti-EGFR Abs for a metastatic CRC, the detection of KRAS mutations on tumour DNA is now mandatory since several recent studies have clearly demonstrated that the presence of KRAS mutations confer a resistance to these therapies. Considering the lack of sufficient data, the detection of KRAS mutations is not recommended in other clinical setting.

The KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-EGFR (epidermal growth factor receptor) antibodies, such as cetuximab (Erbitux) or panitumumab (Vectibix). KRAS mutations are unambiguously linked to a lack of response to these targeted therapies and to a poor outcome. The optimal determination of the KRAS status should be based on coordination between pathologists and biologists. The pathologist must morphologically check the tumor to be analyzed and be sure that the fixatives used are valuable for molecular biology. The pathologist's involvement may also concern the DNA extraction and the KRAS mutations analyses. This involvement has to be included in a multidisciplinary setting in order to get rapid and robust tests for the clinical use. The imperative knowledge of the KRAS status in the management of metastatic disease represents a good example of this multidisciplinary coordination. In the future, the pathologist's role should be extended, considering the emergence of a more and more personalized medicine, integrating efficiency and cost-effectiveness. Thus, the pathologist may contribute to validate new molecular tests and to offer his specific techniques for translational research.

Activating mutations of the oncogene K-ras are found in one third of all human cancers. Much of our knowledge on K-ras signal transduction and its influence on tumor initiation and progression come from in vitro studies with cell lines. However, mouse models of human cancer allow a much more faithful recapitulation of the human disease, and the in vivo perspective is crucial for our understanding of neoplasia. In recent years, several new murine models for K-ras-induced tumorigenesis have been described. They allow new insights into the specific role that oncogenic K-ras proteins play in different solid tumors, and they permit the molecular dissection of the pathways that are initiated by somatic mutations in subsets of cells. Key advances have been made by the use of tissue-specific and inducible control of expression, which is achieved by the Cre/loxP technology or the tetracycline system. From these sophisticated models, a common picture emerges: the effects of K-ras on tumor initiation depend strongly on the cellular context, and different tissues vary in their susceptibility to K-ras transformation.

A better understanding of gliomas biology is now leading to a combined histo-molecular classification of these tumors. In anaplastic gliomas ongoing studies depend on 1p/19q codeletion status and in glioblastomas on MGMT methylation status. Advanced brain tumor imaging elicits a better identification of gliomas evolutive potential of. In low-grade gliomas, the importance of maximal resection and the role of chemotherapy are being increasingly recognized. In anaplastic gliomas, phase III studies have clarified the respective roles of chemotherapy and radiotherapy. In glioblastomas concomitant chemoradiotherapy is the standard. Most targeted therapies, namely anti-EGFR therapies have failed to demonstrate efficacy but anti-angiogenics are promising. The aim of this review is to discuss the main advances in adults' gliomas biology, imaging and treatment.

The epithelial-mesenchymal transition (EMT) is a morphogenetic program that converts epithelial into mesenchymal cells during the embryonic development. This mechanism is frequently reactivated during tumor progression and provides cells with motility and invasive capabilities favoring the metastatic dissemination from epithelial tumors. Various EMT-inducing transcription factors, such as the TWIST proteins, were also shown to inhibit oncogene-induced fail-safe programs (senescence and apoptosis), thereby promoting the progression from benign to malignant stages. Altogether, these observations suggest that EMT could play an important role in favoring both tumor development and metastatic dissemination.

We report three different cases in location with an original occurrence in the oesophagus. The gross appearance showed polypoid pedonculated masses with a whitish cut surface, arising from the submucosa. On microscopic examination, the tumor consisted of spindle cell dispersed in a loose fibromyxoid stroma containing numerous blood vessels and inflammatory cells with abundant eosinophils. At immunohistochemistry, the cells were strongly positive for CD34. Inflammatory fibroid polyp is a rare benign lesion of the gastro-intestinal tract. The pathogenesis of this lesion remains throat and unclear. Diagnosis on biopsy is difficult with various histologic pattern and because the inflammatory fibroid polyp share common pathologic features with digestive spindle cells tumor.

Muir-Torre syndrome, a rare autosomal dominant inherited disease, is characterized by the synchronous or metachronous occurrence of at least one sebaceous gland neoplasia such as an adenoma or carcinoma, with or without keratoacanthoma, and at least one internal malignancy, mostly colorectal cancer. Visceral malignant neoplasms seem to be less aggressive than their sporadic counterparts. Muir-Torre syndrome has been recognised as a subset of Lynch's syndrome, with similar microsatellite instability and germline mutations in DNA mismatch repair (MMR) genes mainly in MSH2 and/or MLH1. We report the case of a 60-year-old man with a Muir-Torre syndrome, presenting an indolent poorly differentiated duodenal carcinoma. Immunohistochemical analysis revealed the loss of expression of MSH2 and MSH6 proteins in tumor cells. According to medical literature, only 16 cases of Muir-Torre syndrome with small bowel carcinoma have been reported to date.

Congenital epulis (CE) of the newborn also known as congenital granular cell tumor or Neumann tumor is an uncommun benign tumour occuring in the anterior alveolar ridge of the jaws. It may interfer with breathing and feeding. In our study, we discuss the clinicopathologic and evolutive caracteristics and the diagnosis problems of this entity.