Various studies of medullary thyroid carcinoma have found its apoptosis rate to be very low. Tumor growth is usually progressive but in some cases, rapid progression and high proliferation are seen. Some mutations of the RET proto-oncogene are thought to have a direct or indirect effect on this clinical process. Five characteristics are significantly associated with poor survival: tumor necrosis, squamous histology, age older than 45 years, oxyphilic tumor cells together with a lack of intermediary cytoplasm cells, and finally, less than 50% of tumor cells immunoreactive to calcitonin. Although recent studies have identified the gene involved in this cancer, its molecular pathogenesis has not yet been elucidated. Medullary thyroid carcinoma is rare, but practitioners must be familiar with it because it presents specific therapeutic and diagnostic problems. Sensitive and specific direct genetic diagnosis of the principal mutation of the RET proto-oncongene is possible in patients with familial thyroid carcinoma or multiple endocrine neoplasia type 2. Screening is based on the immunoradiometric assay of calcitonin levels before and after pentagastrin stimulation in different populations: healthy subjects, persons with family members who have medullary thyroid carcinoma, patients with thyroid nodules or autoimmune chronic thyroiditis. Recently a somatic mutation on RET codon 918 was reported in patients with medullary thyroid carcinoma and those with C cell hyperplasia and multiple endocrine neoplasia together. This finding suggests that this particular mutation may play a role in tumorigenesis. Compared with patients with endocrine neoplasia syndromes type 2A and 2B, these patients appeared to have a syndrome clinically overlapping these, and its genetic basis may be distinct from them. Family members of patients with medullary thyroid carcinoma must be screened for this inherited disease. The mutations associated with medullary thyroid carcinoma and parathyroid tumors together appear to be closely related to the centromeric region of chromosome 10. At three months of age, Wag/Rij rats show hypersecretion under secretagogues and C cell hyperplasia; both signs are described as "pretumoral" in humans. A battery of markers are useful even though the gene for multiple endocrine neoplasia type 2 gene has recently been thought to be located in the pericentromeric region of chromosome 10 in white Europeans.

Neurofibromatosis 2 (NF2) is a rare autosomal dominant disease whose hallmark is the development of bilateral vestibular schwannomas.

The management of gliomas in daily clinical practice is challenging. It requires a multidisciplinary and coordinated approach involving neurosurgery, radiotherapy and, finally, chemotherapy. Important progress has been made during the last years with the introduction of a combined treatment associating standard radiotherapy with concomitant chemotherapy using temozolomide, a novel alkylating agent. For the first time in many years a new treatment strategy translated into a significant prolongation of survival. In parallel, molecular markers (e.g. loss of heterozygosity on chromosomes 1p and 19q or methylation of the methyl-guanine methyl transferase [MGMT] gene promoter) allowed for identification of distinct subtypes of glioma or prediction of treatment response. In this "Practical Guide", we describe the daily practice and aim at answering some common questions in the management of patients suffering from glioblastoma, astrocytoma, oligodendroglioma and low grade glioma. The therapeutic options presented here are based on evidences from the literature. In the absence of documented evidence, the empirical choices from our local practice are explained and justified.

During the last 10 years, molecular testing of soft tissue tumors has become increasingly important, not only in the diagnostic approach of these lesions, but also regarding their prognosis and pathogenesis. A subset of soft tissue sarcomas bear chromosomal abnormalities including reciprocal translocations, deletions, mutations and amplifications, which turned out to be histotype specific. Beside their diagnostic value in sarcoma typing and subtyping (always in an appropriate clinical and histologic context), some of these abnormalities may also impact on treatment response and/or on prognosis. The aim of this review is to provide an overview of the most informative soft tissue sarcoma chromosomal abnormalities, and to give some clues about why and how we should detect them. Some sarcoma types (Ewing sarcoma, rhabdomyosarcomas, synovial sarcoma, well-differentiated/dedifferentiated and myxoid liposarcomas, gastrointestinal stromal tumors--GIST, malignant rhabdoid tumor) will be studied in more detail and the potential implication of these abnormalities in tumor genesis, growth, and maintenance will be briefly discussed.

The histones, that wrap the DNA to form the nucleosome core, are targeted by diverse post-translational modifications. How those modifications affect DNA accessibility and chromatin folding is a fundamental biological issue. Furthermore, tremendous amounts of data suggest that the loss of specific modifications as well as an inappropriate ectopic pattern of modifications at given loci contributes to the development of several human syndromes as well as cancers. In this review, we focus on the current knowledge of the regulation and impact of histone H4 lysine 16 acetylation on the genome. Recent discoveries highlight its crucial involvement in events such as transcription regulation, chromatin specialization, chromosome compaction and tumoral progression.

Von Hippel-Lindau (VHL) disease is the main cause of inherited kidney cancer and the model of tumoral angiogenesis. This rare syndrome is caused by germline mutations of the VHL tumor-suppressor gene that predispose to the development of a panel of highly vascularized tumors. Main manifestations include CNS and retinal haemangioblastomas, endolymphatic sac tumors, clear-cell renal cell carcinomas (RCC), phaeochromocytomas and pancreatic neuroendocrine tumors. The VHL gene plays a major role in regulation of the oxygen-sensing pathway by targeting the hypoxia-inducible factor HIF for degradation in proteasome. Somatic inactivation of the VHL gene occurs also in most sporadic RCC. Recent progress are pawing the way for the development of antiangiogenic targeted therapies that have already shown promising results in metastatic sporadic RCC.

A meta-analysis of recent data from the literature underscores the considerable body of present knowledge concerning prostate carcinogenesis, in part due to the numerous molecular biology tools now at our disposal. As concerns early events, much interest is being paid to modifications in the expression of GSTP1 and NKX3.1 occurring in totipotent stem cell populations. The discovery of fusion genes implicating TMPRSS2 and ERG (and, on rare occasions, other ETS family transcription factors) constitutes a major advance. Under physiological androgenic stimulation, the presence of these fusion genes leads to overexpression of genes involved in cell growth and differentiation. Concomitantly, alterations in numerous signalling pathways (growth factors, Wnt-beta catenine, PI3K/Akt) are responsible for the onset of an aggressive tumor phenotype. Hormono-independence is currently explained by an amplification of, or mutations in, androgenic receptors. These are facilitated by genomic instabilities linked to alterations in proteins which regulate gene expression, such as EZH2, and by the influence of the tumor microenvironment. Disturbances in the interactions between tumor cells and the microenvironment contribute to local extension of the tumor. Changes in the expression of E-cadherin are responsible for modifications in cell adhesion to the extracellular matrix. The expression of metalloproteases and of angiogenic factors favors tumor dissemination. Finally, the bone tropism in prostate metastases is probably linked to osteomimetic properties of prostate tumor cells which are capable of expressing certain proteins involved in bone remodelling, such as Runx-2, BSP (bone sialoprotein) and BMP (bone morphogenetic protein). Numerous studies remain to be carried out in order to correlate the identified genetic profiles and molecular anomalies with tumor prognosis. Nevertheless, the possibility of decrypting these anomalies for use in therapeutic applications is encouraging.

Questions raised during gemcitabine development reflect non small-cell lung cancer (NSCLC) history during last 10 years. Third generation therapies (gemcitabine, vinorelbine and taxanes) combined with platinium compounds are now to be prescribed in almost all clinical situations, from surgically removed tumors to metastatic diseases. The 30% response rate usually reported in advanced disease (with a median survival of 10 months) has to be improved and a more global approach is nowadays mandatory, including targeted agents. This review sum-up the clinical situations in which gemcitabine can be prescribed (advanced disease), or shall be prescribed (adjuvant setting, combination with anti-angiogenic agent or EGFR inhibitors), and highlight opening questions.

Our patient was refered to hospital for a malignant mesthelioma 22 years after the prior diagnosis of a mesothelioma in his brother. Their family history included others cancers. No exposure to asbestos was documented in brother's history. Literature is rich with family mesothelioma reports. Most of them are linked to an occupationnal asbestos exposure. But, some studies suggest that family genetic factors are involved in the development of mesothelioma: (genetically transmitted mesotheliomas in Turkish families in Cappadoce, family clustering of cancers including mesotheliomas, inhibition of tumor suppressor genes (INK4A, p53, Nf2...), a small proportion of mesothelioma among asbestosis exposed workers. Many studies suggest an interaction between genetic and environment. A genetic predisposition could lead to an increased susceptibility to carcinogenic factors.

Ovarian cancer is the leading cause of death from gynaecological malignancy, especially because of late diagnosis. The objective of the study was to provide the clinician with current concepts regarding prevention of ovarian cancer.

Erythrocytosis is a rare disorder in childhood and is mainly secondary to causes such as long-term chronic cardiopulmonary diseases or haemoglobin dysfunction. In some cases, polycythaemia is found when renal, hepatic or cerebellar tumours are diagnosed. Polycythemia vera (PV) is uncommon in paediatrics and usually clinical and biological features are used to diagnose and classify PV. The V617F mutation of JAK-2 has been described recently and is found in almost 90% of adult patients with PV. This mutation allows now a reliable and early diagnosis. Therapeutic management is based on phlebotomy and cytoreductive therapy. In young adults and children, interferon alpha is theoretically superior as it is effective and there is no risk of inducing leukemia. We report here a case of PV in a 10-year-old girl with the V617F JAK-2 mutation.

Introduction. The development of a DNA based diagnostic test has allowed for the genetic screening of many hereditary diseases. In addition to the identification of the deleterious gene, this screening process has led to the recognition of developing illnesses at high risk. In recent years, a number of genes predisposing to an inherited cancer syndrome have been identified.

To study by flow cytometry (FCM) the ploidy and the cellular cycle of nodular hidradenoma (NH) and hidradenocarcinoma (HC) and to assess the prognostic utility of this technique in such tumors.

Trastuzumab (Herceptin) is the first humanised monoclonal antibody targeting the HER2 antigen in breast cancer. HER2 receptor has been individualised 20 years ago. During the past 10 years, trastuzumab administration has radically modified the prognosis of the patients that are treated for HER2 positive breast cancer. Its efficacy has been demonstrated in the metastatic and adjuvant settings. While, trastuzumab based-regimens became the standard of care in the treatment of HER2/neu positive breast cancer, the optimal combination (concurrently or sequentially) to chemotherapy and radiation therapy is still unknown. Indeed, while the concurrent administration of trastuzumab and anthracyclines is not recommended because of a high risk of cardiac toxicity, there is no published data on the best sequence of trastuzumab and radiation therapy administration, particularly when internal mammary chain is involved. The benefit/risk ratio of the concurrent and sequential administration of trastuzumab with chemotherapy and radiation therapy will be discussed in this review.

This study was designed to demonstrate that the study of cell ploidy on biopsies of clinically localized prostate cancers can contribute to the diagnosis of a tumour extending beyond the prostatic capsule and can complete imaging for local staging.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting young women and presenting with recurrent pneumothorax.