Colorectal cancer is the second leading cause of death in Northern countries and need a national screening program to reduce mortality and improve quality of life. Screening has to be cost-effective and acceptable for patients. Many screening tools, invasive or not, are existing and often debated: FOBT, sigmoidoscopy and complete colonoscopy. New tools are in development and have to be evaluated in current practice: virtual colonoscopy, new endoscopic technologies, DNA on faeces or proteomics with markers in serum.

During malignant transformation, the malignant cell accumulates epigenetic abnormalities that do not alter the DNA sequence but are transmissible during divisions and modify genes expression. The methylation of CpG islands in the tumor suppressor genes (TS genes) promoters inhibits their transcription ; it is a mecanism of gene inactivation as frequent as allelic deletions. The methylation profile (or panel of methylated genes in a tumor), similarly to allelic deletions, varies with the tumor histology. Within head and neck squamous cell carcinoma (oral cavity, larynx and oropharynx), 19 genes have been analysed, among them 5 are frequently methylated, i.e. : p16, ECAD, DAPK, MGMT et TIMP3. The method of methylation analysis, based on a bisulfite treatment followed by a PCR amplification, is sensitive and specific enough to allow the detection of abnormalities in biological fluid that drain the tumor or in circulating tumoral DNA. In the head and neck squamous cell carcinoma, correlation between the methylation profile in tumor and paired saliva is excellent ; thus methylation analysis in saliva is a very promising approach for early cancer detection in high risk patients or for the post treatment follow up and rapid diagnosis of relapse. The methylation signature might also reflect the tumor prognosis and complete the histology to define the diagnosis. Finally, DNA methylation is reversible with demethylating agents, a new avenue for cancer therapy in association with conventional chemotherapy.

Dermatofibrosarcoma protuberans (DP) is a rare, slow growing dermal neoplasm of intermediate malignancy. It is made of spindle-shaped tumor cells in a storiform pattern often positive for CD34. The preferred treatment for DP is a surgical wide excision with pathologically sane margins of 3 cm. At the cytogenetic level, DP cells are characterized by either supernumerary ring chromosomes composed of sequences derived from chromosomes 17 and 22 or more rarely of translocations t(17;22). Rings have been mainly observed in adults whereas translocations have been reported in all pediatric cases. These chromosomal rearrangements lead to the formation of a specific fusion gene : COL1A1-PDGFB detected in rings as well as in translocations. DP is therefore a unique example of tumor in which the same molecular event occurs either on rings or linear translocation derivatives and the chromosomal abnormalities display an age-related pattern. So far, the COL1A1-PDGFB fusion gene remains the only fusion gene identified in this tumor. It is also present in variant forms of DP such as giant cell fibroblastoma, Bednar tumor, adult superficial fibrosarcoma and the granular cell variant of DP demonstrating that these tumors are not distinct entities but morphological variants of DP. The breakpoint localization in PDGFB was found to be remarkably constant, placing exon 2 of PDGFB under the control of the COL1A1 promoter. In contrast, the COL1A1 breakpoint was found to be variably located within the exons of the alpha-helical coding region (exons 7-47). No correlation between the breakpoint location in COL1A1 and the age of the patient or any clinical or histological particularity has been established. Moreover, no preferential breakpoint appears to be more particularly linked to one or another variant of DP. The COL1A1-PDGFB fusion gene is detectable either by multiplex RT-PCR with a combination of forward primers designed from a variety of COL1A1 exons and one reverse primer for PDGFB exon 2, or by in situ fluorescence hybridization (FISH) on interphase nuclei from frozen or fixed paraffin-embbeded sections. The COL1A1-PDGFB fusion gene is not found in approximately 8% of DP cases, suggesting that genes other than COL1A1 or PDGFB might be involved in a small subset of cases. It has been proposed that PDGFB acts as a mitogen in DP cells by autocrine stimulation of the PDGF receptor. The PDGF receptor tyrosine kinase antagonist imatinib mesylate has recently been used in clinical trials; its efficiency has been demonstrated in several cases, which allows it to be considered as a novel treatment strategy for metastatic or locally advanced DP.

History of diabetes, chronic pancreatitis for more than 15 years, and mucinous tumors such as mucinous cystadenoma and intraductal papillary mucinous tumors of the pancreas are all risk factors for pancreatic adenocarcinoma. Recent diabetes with gastrointestinal disorders or weight loss, acute idiopathic and recurrent pancreatitis, the discovery of a cystic lesion in the pancreatic region -all these require exhaustive imaging of the pancreas. In other words, the diagnosis of these benign tumors that risk degeneration into malignancy must not be neglected because practically it is the only way to provide early treatment of pancreatic cancer. Early diagnosis of pancreatic cancer remains difficult today in the absence of reliable serum markers and clearly specific clinical situations at its onset.

Meningiomas account for approximately one-fourth of all primary central nervous system tumour, arising from arachnoidal cells surrounding brain and spinal cord. They usually affect older adults, particularly women. Ninety percent of meningiomas are slow growing benign tumours. Meningiomas are revealed by various symptoms including neurologic deficits and epileptic seizures. Surgery remains the treatment of choice. Fractionated radiotherapy or stereotactic radiosurgery are used for meningiomas that are recurrent, surgically inacessible, partially excised and either atypical or malignant. Most meningiomas have good long-term prognosis after treatment, some dysplay aggressive clinical behaviour leading to increased patient morbidity and mortality.

High grade gliomas are the most frequent and malignant primary brain tumours in adults. Prognosis depends on age, performance status and histological grade. Associated with symptomatic treatments, surgery, radiotherapy and chemotherapy represent the main weapons of the specific multidisciplinary therapy of malignant gliomas. Surgery is necessary for histological diagnosis. In malignant gliomas, surgery may improve survival in case of complete removal, and debulking provides an improvement of the quality of life and a symptomatic relief. Radiation therapy has been shown to improve survival in malignant glioma. The place of chemotherapy is growing not only for anaplastic oligodendrogliomas, more chemosensitive (particularly when they harbor 1p19q codeletions), but also for glioblastomas patients, which have been shown to benefit from radiotherapy plus concomitant and adjuvant temozolomide. This effect was particularly clear for patients with MGMT inactivation in the tumour, confirming here also the impact of molecular biology for future management of gliomas.

Cutaneous mastocytosis represent the most frequent form of mastocytosis, rare diseases, defined by an abnormal accumulation and proliferation of mastocytes in one or more organs. Cutaneous mastocytosis more often appear early in childhood and usually resolve spontaneously by the time of puberty. In adult, cutaneous mastocytosis rarely involute and are frequently associated to extracutaneous involvement and so, are in fact systemic mastocytosis. Clinical presentation of cutaneous mastocytosis includes polymorphous cutaneous lesions linked to mastocytes skin infiltration often associated to acute episodes (lesional or systemic flush) due to mast cells degranulation. The cause of mastocytosis is unknown. Several mutations of the c-kit proto-oncogen coding for the transmembrane receptor kit of the stem groth factor, factor of maturation, proliferation and activation of mastocytes, are often observed. Currently, the treatment of cutaneous mastocytosis is mainly symptomatic.

The FSH receptor presents several polymorphisms. Two of them, located at codon 307 and 680, are the most frequent. Threonine can be substituted by alanine at position 307 and serine can be substituted by asparagine at position 680. The two most frequent allelic combinations are Thr(307) -Asn (680) (60%) and Ala(307) -Ser (680) (40%). As the allelic variants at codon 307 and 680 are almost invariably associated, most of the studies assessed only one codon (680) and classified the women as homozygous (Ser/Ser ou Asn/Asn) or heterozygous (Asn/Ser). Several studies aimed to correlate the follicle-stimulating hormone receptor polymorphism and ovarian function. Women homozygous for the Ser (680) variant have higher follicular FSH levels and longer follicular phase length, which suggest a lower sensitivity to FSH. The FSH receptor genotype would also influence the sensitivity to exogenous FSH: as regards ovarian stimulation, higher recombinant FSH doses are needed for Ser/Ser homozygous women. The analysis of polymorphism in women with premature ovarian failure did not show a link with any particular allelic variant. In women with polycystic ovaries, the distribution of the allelic variants greatly varies from one study to another.

Acute promyelocytic leukaemia (APL) account for approximately 10% to 15% of all AML in most reports. Clinical features includes the presence in 80% to 90% of patients of a severe hemorrhagic syndrome, a specific balanced translocation between chromosomes 15 and 17 with a fusion of a large pert of the retinoic acid receptor a gene (RARa) on chromosome 17 to a part of the promyelocytic leukaemia (PML) gene on chromosome 15. More than 75% of patients (under 65 years of age) can be cured, with the application of a combination of anthracyclines and all-trans retinoic acid (ATRA), followed by maintenance therapy.

The Lynch syndrome or HNPCC, is due to a mutation of the genes pertaining to the system MMR. This frequency varies from 1/1000 to 1/400. It's responsible for 6% of endométrial cancers, 2% of ovarian cancers and 1 to 3% of colorectal cancers. A good knowledge of this syndrome is necessary for doing the diagnosis and adjustment of gynaecological and colorectal follow-up. The authors report four cases in Lynch syndrome family.

Diagnosis of nonpalpable breast lesions too often requires a breast biopsy or tumorectomy.

Colorectal serrated polyps are heterogeneous epithelial lesions characterized by a serrated architecture. They include the classical hyperplastic polyps and the much rarer serrated adenomas and mixed polyps. Whereas serrated adenomas are composed of an unequivocal adenomatous epithelium with architectural serrated, mixed polyps include two separate hyperplastic and adenomatous components. During the past few years, another type of serrated polyp with only very subtle proliferation abnormalities has been described. These atypical serrated polyps may occur either sporadically or in the context of colorectal polyposis. Despite their close resemblance to traditional hyperplastic polyps, some authors argued that they should be regarded as authentically neoplastic lesions and have proposed to call them "sessile serrated adenomas". Their malignant potential requires their removal when discovered during colonoscopy. This article reviews the histological features, the endoscopic appearance, the natural history and the molecular phenotype of the different categories of serrated polyps and introduces the concept of "serrated neoplastic pathway" in the development of colorectal cancer.

DNA microarrays allow simultaneous measurement of the expression of several thousand genes in a biological specimen. This technique represents a major advance in the analysis of tumour biopsies. It may be used to refine the anatomical- pathological diagnosis at a molecular level and thus lead to better diagnostic and prognostic classification and improved therapeutic decisions.