The transcription factor NF-kappa B has attracted widespread attention among researchers. NF-kappa B displays some original characteristics including rapid regulation, the wide range of genes that it controls and its probable involvement in several diseases. In resting cells, NF-kappa B is kept in an inactive form in the cytoplasm where it is bound to a member of the I kappa B family of inhibitory proteins. NF-kappa B can be activated by exposure of cells to physiological as well as non physiological stimuli. Upon cell activation, the inhibitors are modified through site specific phosphorylations which target them for subsequent ubiquitination and proteolytic degradation by the proteasome. Removal of the inhibitor unmasks the nuclear localization signals on subunits of NF-kappa B. Free NF-kappa B moves to the nucleus where it binds to target DNA elements and activate transcription of genes encoding proteins involved in immune responses, inflammation or cell proliferation. NF-kappa B could be considered as a co-ordinating element in the body's responses to situations of stress, infection or inflammation. A tight regulation of NF-kappa B seems to be crucial since a dysfunction could promote pathogenic processes including AIDS (acquired immunodeficiency syndrome), rheumatoid arthritis and cancer. Additionally, it will be important to understand the exact roles for NF-kappa B in regulating apoptosis. NF-kappa B is now regarded as a good therapeutic target and the development of specific inhibitors should lead in the next future to novel therapeutics.

The population with Down's syndrome has a different cancer profile compared to the general population, even after taking into account issues of survival and ageing. Several solid tumours are unusually rare, whereas in contrast leukaemias are increased. In addition, few studies are available on this topic. We therefore decided to conduct a mortality study based on the INSERM national mortality statistics in France comparing over a 24 year period deaths from female breast cancer in the general French population with the cancer deaths in women with Down's syndrome. Only 5 deaths with Down's syndrome could be found compared to 68.98 expected based on national statistics. This clear reduction in risk agrees with other studies available in Down's syndrome patients. This observation could be partly explained by over expression of genes linked to gene dosage effects on chromosome 21, playing a role in cell growth, differentiation, survival and death. An additional protective effect could come from the marked and continued decreased exposure to oestrogens, starting in utero for women with trisomy 21 and lasting all over life.

The course of hepatitis B virus (HBV) infection may be influenced by the host immune response. A prospective study was carried out in ninety-eight subjects (mean age = 23 years) HBs antigens carriers of hepatitis B and living in Dakar, Senegal. We analysed the HLA-A, -B, and C antigens distribution compared to that one of a control (HBs negative) healthy senegalese population (n = 96) living in Dielmo village where a longitudinal study was set-up since 1990. The HLA class I typing was performed by microlymphocytotoxicity assays. The most frequent HLA-A, -B, -C antigens found were: locus A: A23 (33.6%), A2 (25%), A30 (25%), locus B: B8 (31%), B7 (16.3%), B58 (11.9%), B35 (11%), B49 (11%), B53 (10.8%) and locus C: Cw7 (39.1%), Cw17 (39.1%), Cw3 (36.9%), Cw4 (36.6%). Significant differences (P < 0.001) were found between the donors and the control group for the following HLA antigens: A1, A23, B8 and Cw3. The detection of HBe antigen was positive in 26/84 blood donors. It was observed a significant difference (p < 0.01) between positive and negative HBe donors for HLA-A1 allele with an odds ratio of 6.25. All the donors carrying the HLA haplotype: A1-B8-Cw7 (11.5%) were positive in HBe antigen. HLA: B8-Cw7 haplotype (detected in 8.5% of positive donors) seems to be likely associated with a liver cancer according to many reports. An adequate follow-up should be set-up for positive HBe subjects carrying a susceptible HLA type.

Tissue microarray technology is a new method used to analyze several hundred tumor samples on a single slide allowing high throughput analysis of genes and proteins on a large cohort. The method consists to core tissues from paraffin-embedded tissue donor blocks and placing them into a single paraffin block. Despite the low amount of tissue analyzed by tissue microarray, different studies have demonstrated a high concordance of protein expression between this technique and the conventional tissue sections.

Malignant fibrous histiocytoma (MFH) has come to be regarded as the most common malignant neoplasm of the mesenchymal soft tissues. It designates a spectrum of tumors which share morphologic features that allow their inclusion in a distinct clinicopathologic setting, although being not uniform in their histogenesis and pathogenesis. Clinicopathologic variants include the following: the storiform-pleomorphic form of MFH, the myxoid type of MFH, the giant cell type of MFH and the inflammatory type. The latter group, the angiomatoid variant, has been reclassified within the fibrohistiocytic tumors of low malignant potential. Tissue culture, ultrastructural and immunohistochemical studies have both endorsed or refuted the validity of the concept. As a whole, these morphologic studies which attempted to characterize MFH were not able to delineate specific markers or to describe the phenotype of this sarcoma of supposed fibrohistiocytic lineage. There is growing evidence that MFH is a second component in another sarcoma and represents a morphologic modulation resulting from tumor progression. Recent cytogenetic and molecular genetic investigations are consistent with that hypothesis: a comparative analysis between the most frequent genomic imbalances observed in series of MFH and leiomyosarcomas (LMS) demonstrated that both tumors had similar recurrent imbalances. Immunohistochemical and molecular biologic investigations have shown similar targets of chromosome deletions in both tumors. A new classification of soft tissue sarcoma based on molecular parameters is nevertheless premature. The morphologic characterization of MFH and its sub-types provides the clinician with unique information in the management of these tumors, by identifying a spectrum of tumors with well-recognized clinical profiles.

Thanks to recent progresses in colonoscopy non-polypoid lesions, even very small, can be detected and removed per endoscopy. They are defined endoscopically as flat polyps or flat lesions and correspond microscopically to neoplasia in more than 30% cases. This review presents the definitions and different types of flat adenomas and flat early adenocarcinomas as established by Japanese authors. The use of appropriate definitions and classifications and the need of a perfect method in preparing the samples before microscopic examination are underlined. Flat adenocarcinomas tend to invade the submucosa at a smaller size than carcinomas arising in polypoid adenomas. They result either of the malignant transformation of flat adenomas or of a de novo type histogenesis. Flat early adenocarcinomas invading the submucosa and measuring less than 1 cm belong to the latter category.

Genetics of neuroendocrine tumours is mainly related to major inherited syndromes which predispose to the development of tumours in endocrine glands. Clinical and genetic studies on multiple endocrine neoplasia (MEN) syndromes show the diversity and complexity of cellular and genetic pathways involved in endocrine tumor genesis. Nevertheless, we might expect that recent cloning of most of the genes involved in MEN and related syndromes, has been a powerful and historical step to help clinicians in differential diagnosis of MEN and related diseases, mainly in cases which show familial association of various types of endocrine tumors. To date, 4 to 6 genes may be commonly analyzed and a single patient diagnosed for a specific syndrome, thus leading to a better clinical and therapeutical follow-up for patients and related predisposed individuals.

Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is the subject of conflicting discussions and the potential link has implications for the diagnosis, prognosis, and treatment. Clinical aspects of adamantinomas are described: location, age, gender, symptoms, imaging, diagnosis, treatment, clinical course, prognosis. Histopathology is extensively covered for usual and peculiar forms. Immunohistochemical results are described and discussed. Data of electron microscopy, cytological findings, and DNA flow cytometry are also reported. The putative association with osteofibrous dysplasia is the subject of an extensive development with the report of the personal experience and works of the authors, and arguments for viewing osteofibrous dysplasia and "osteofibrous dysplasia-like" adamantinomas as precursor lesions of classic adamantinomas are favoured.

The small but significant increase in risk of discovering breast cancer in women with hormone replacement therapy and the recent discussion of coronary benefit of this treatment have led many authors to insist on the necessity to evaluate the benefit/risks ratio before administration. This evaluation is particularly important for women that are already at high risk of breast cancer because of some genetic predisposition, family history or some benign breast diseases. In these cases, it is important to evaluate the absolute risk of breast cancer, to define the patient's needs more precisely, to specify menopausal symptoms; it is also important to evaluate the risk of osteoporosis, to review the various therapeutic possibilities, which are not only estrogen/progestin treatments (there are alternative treatments), and to give the patients honest information. Before obtaining the results of current trials, we are proposing here a pragmatic attitude and a decision algorithm to adopt a therapeutic attitude more easily which will be decided together by both patients and their physicians.

The undifferentiated carcinoma of nasopharyngeal type (UCNT) is highly prevalent in South East Asia countries and has intermediate incidence in Tunisia, where Epstein-Barr virus constitutes one of the key factors of oncogenesis. Our preliminary results, in 3 patients with UCNT, show an elevated rate of EBV antibodies and a latent infection (type II) (expression of LMP and absence of ZEBRA by immunohistochemical reaction) and a positive staining with EBERs probe by in situ hybridation (ISH) in all cases. These results confirm a close association between EBV and tunisian UCNT. Moreover, the use of HIS technique for detection of EBERs constitutes an additional and formal argument of this association.

Schöpf-Schulz-Passarge's syndrome is a rare autosomal recessive genodermatosis associating hypodontia, palmoplantar keratoderma, cysts of the eyelid margins, onychodysplasia and hypotrichosis. We report two new cases.

Radiation induced tumors are a possible (very) late complications of radiotherapy. The evaluation of the risks of radiation-induced tumors has been presented in different epidemiological studies, with the evaluation of the relative risk for different tissues. But, the genetic studies are rare, and no global theory exists. Two cytogenetic profiles are described, one with translocations and one with genetic material losses, evoking two different genetic evolutions. Two questions are stated. What are the radiation-induced genetic mechanisms? Is it possible to differentiate the radiation-induced and spontaneous tumors with genetic approaches? With 37 cytogenetic cases, 12 analyzed in our laboratory, the radiation-induced tumors were characterized by genetic material losses. An anti-oncogenic evolution is probable. A new molecularly study confirm these results. Only thyroid tumors do not have this evolution. For tumors with simple karyotype, like meningioma, radiation-induced tumors seem to be more complex than spontaneous tumors. But for the others, the differentiation is impossible to be done with cytogenetic. The mechanism of the chromosomic material losses in unknown, but some hypothesis are discussed.

Since the establishment of human karyotype in 1956, human cytogenetic has quickly progressed. The description of the Philadelphia chromosome in 1960 led up to new applications of cytogenetic in the fields of hematology and oncology. The initial techniques allowed only uniform staining of chromosomes, limiting the detection of most structural rearrangements. Many approaches aimed to gain a better knowledge of chromosomal structure, a better understanding of rearrangements, and a better identification of the chromosomes were developed: autoradiography, banding techniques, electronic microscopy. Since 1980, new developments in clinical cytogenetic and molecular biology have occurred. In situ labeling using non-radioactive probes onto chromosomes and nuclei was developed: fluorescence in situ hybridization (Fish) was born. Fish allows detecting many chromosomal abnormalities of number and/or structure. The major limitation of this technique is that its use should be based on known indications for the choice of the probe. Multicolor karyotype (M-Fish or Sky), the most recent development of Fish on metaphase spreads, allows to overcome this limit. As shown here in three examples, M-Fish allows to describe precisely complex rearrangements in hematological malignancies and solid tumors. Finally, if no metaphase is available, comparative genomic hybridization (CGH) can be performed to detect and simultaneously localize on chromosomes gains or losses in genomic DNA.

Bladder cancers are classified as: transitional cell carcinoma (TCC), the most frequent in Europe/USA, squamous cell carcinoma (SCC), more frequent in the Middle East and in Africa, adenocarcinoma and small cell carcinoma, rare. TCC exhibit pseudo diploid karyotypes with only a few anomalies in early stages, evolving towards pseudo-tetraploides complexes karyotypes. Partial or complete monosomy 9 (-9) is an early event, found in half cases. Deletion (11p) or -11 is found in 20-50% of cases, more often in high grade and invasive tumours. Del(13q) is found in 25% of cases and correlated with high grade/stage; tumours with Rb alterations are invasives. Del(17p) is a late event, found in 40% of cases; P53 alterations are correlated with grade and stage, tumour progression, and a worse prognosis. Del(1p), i(5q), +7, and many other rearrangements - more often deletions than duplications - are frequently found. These losses of heterozygocity point to a multistep complex process involving tumor suppressor genes. In SCC, monosomy 9 is also an early event, even more frequent than in TCC; homozygous deletion of P16 is frequent. Trisomy 7 seems to be more frequent than in TCC. Chromosome 17 is often implicated, especially in high grades/stages; the profile of mutations of P53 is different from what is found in TCC. Allelic losses of 3p, 8p, 9p, 9q, 17p are frequent. The karyotype is more complex in advanced grades/stages, as in TCC.

Chromosomal study in malignancy has demonstrated the pivotal role of somatic chromosomal rearrangements in oncogenesis and tumoral progression. Structural or quantitative these abnormalities can now be studied in great details with the various Fish techniques, including CGH on chromosomes or in a near future on micro arrays. The multistep pattern of most solid tumors is characterized and their genomic abnormalities more and more used for the diagnosis and the prognosis.

Cowden's disease is an autosomal dominantly inherited syndrome characterized by mucocutaneous lesions and multiple hamartomas. We report here a 12 years-old boy case with craniomegally, intestinal polyps, epilepsy and multiadenomatous goiter. All the lesions were beginnings. The predisposing genetic defect has been assignated to chromosomal 10 (PTEN-gene mutation). A long term follow-up is necessary because of the risk of malignancies.