Nucleolar Organisers (NORs) are intranucleolar segments of DNA coding for ribosomal RNA. The agyrophilic proteins (AgNOR) associated with NORs allow them to be cytolabelled on paraffin sections. The number of NORs (NOR index) is correlated with cellular proliferation and has a diagnostic and prognostic value in neoplastic disease. The AgNOR method was analysed in a series of 37 superficial bladder tumours with different clinical courses. The NORs were counted in normal urothelium, on superficial tumours used to establish the diagnosis of the disease and on recurrent superficial tumours. The NOR index was 4.54 for normal urothelium, 5.89 for non-invasive superficial tumours, 7.33 for invasive superficial tumours, and 9.75 for invasive recurrences. These results demonstrate an increase in nucleolar argyrophilia with invasion and invasive potential of superficial bladder tumours which were initially homogeneous for stage and grade. The AfNOR method could constitute a new method of early histoprognostic evaluation for urothelial tumours.

During the natural history of a tumor, cancer cells become more and more aggressive and their increasing malignancy leads usually to the patient's death. The expression of malignant properties by tumor cells is manifested by the occurrence of metastases and is the result of an overexpression of molecules that are normally or barely non expressed by the normal cell progenitors. These molecules can be involved in cell attachment (receptor to the extracellular matrix), in proteolysis (collagenases), in angiogenesis (b FGF), in adhesion to endothelial cells, in resistance to the immune system. The genetic instability of tumor cells favors the amplification, mutation and gene translocation events, resulting in the activation of some genes or/and oncogenes which might direct the expression of the malignant properties. Finally, metastatic cells have been shown to have a growth advantage over non metastatic cells, so that metastatic cell population becomes ultimately numerously dominant in the primary tumor. The current knowledge about the malignant cell properties allow us to begin to understand how a cancer cell becomes metastatic and how the metastatic dissemination is usually an ineluctable process.

The prognosis of chronic myelocytic leukemia is a current topic owing to the new treatments that have been proposed for this malignant blood disease which, a few years ago, was lethal within 3 to 4 years due to the inescapable occurrence of the terminal acute transformation. Beside bone marrow allograft, which is known to have cured a non-negligible number of patients, the most recent use of interferons offers a reasonable therapeutic alternative to those patients who cannot be allografted. The identification of prognostic variables at the time of diagnosis has become necessary for a better determination of therapeutic indications. The analysis of large published series has made it possible to construct mathematical models which have proved efficient and have been confirmed by prospective studies. The value of new techniques, such as molecular biology, to refine the mathematical models remains to be demonstrated.

Although epidemiologic studies have clearly demonstrated the importance of the hepatitis B virus in the genesis of hepatocellular carcinoma, the molecular basis for this tumorigenic effect is still under debate. Studies of woodchucks infected with a virus closely related to the human hepatitis B virus suggest that integration of the viral DNA in the host genome often plays a direct role by activating myc cellular oncogenes through insertional mutagenesis. A similar mechanism involving other cell genes has been found less frequently in human hepatocellular carcinomas. The human hepatitis B virus may contribute to tumorigenesis in a more indirect fashion, by inducing preneoplastic liver lesions which gradually become malignant.

Hepatocellular carcinomas in woodchuck were characterized for woodchuck hepatitis virus integration near c-myc oncogene. In one tumor, viral integration resulted in overexpression of a c-myc viral cotranscript. In a second tumor, viral insertion, 600 bp upstream of c-myc exon 1, was associated with increased levels of normal c-myc mRNA. These results demonstrate that integration of woodchuck hepatitis virus near a proto-oncogene can contribute to the genesis of liver tumors. From a comparison of a single hepatitis B virus (HBV) integration site in a human hepatoma with the corresponding unoccupied site have shown HBV DNA insertion in a putative cellular exon. This exon presented striking similarity to the DNA-binding domain of the thyroid/steroid hormones receptors. The corresponding cDNA has been isolated (hap gene) a shown to encode the retinoic acid receptor. It is most probable that consequent to HBV insertion, has became inappropriately expressed as an altered chimaeric gene retinoic acid receptor, thus contributing to the cell transformation. As for woodchuck these results strongly support the possibility that HBV may play a direct role in liver carcinogenesis by insertional mutagenesis.

Fetal cystic hygroma (CH) are congenital malformation of the lymphatic system which are seen in antenatally ultrasonography from the end of the first trimester of pregnancy. From a 13 CH retrospective study, the authors discuss the ultrasound diagnosis, the prognosis and the management of CH. In our study, CH is associated with lymphedema (69%), hydrops (46%), diminution of amniotic fluid (69%) and other abnormality (31%). In all cases a diminution or an absence of fetal movement are found. In seven cases a cytogenetic analysis are performed on amniocentesis or fetal tissues: there are five 45XO, one 47XX + 13 and one 46XX. In six cases the chromosome culture failed: two male phenotypes and two histologic appearances of chromosomic anomaly. The prognosis depends on chromosome analysis, other ultrasound abnormality and the size of CH. It is usually fatal in utero. If chromosome anomaly are found, a genetic counsel is proposed.

The evidence that genetic factors are of some importance in the etiology of cancer originates has been determined by genetic epidemiology, molecular biology, cytogenetics. Genetic counselling is one of the possible strategies for controlling cancer through genetics. Genetic counselling in this field more often concerns the family of the affected individual than the individual himself. Its aim is to develop a family oriented preventive medicine.

N-myc amplification and ploïdic index are important prognosis factors in neuroblastoma. Combined overexpression of the multidrug resistance gene, MDR1 and of Glutathion-S-Transferase, GST-pi may be related to the response of tumors to chemotherapy. Measurements of these parameters may contribute to define responders and non-responders to chemotherapy and provide the clinician with additional criteria to manage treatment.

Forty-percent of retinoblastomas are due to a mutation inherited as an autosomal dominant trait with a high penetrance. Cytogenetic forms of retinoblastoma have led to the location of the gene, to the identification of numerous chromosome 13 specific DNA polymorphisms, and to the cloning of the gene. Intragenic DNA polymorphisms are now known. Using Southern blot hybridization, study of the mutation is possible either by direct analysis or by an indirect approach using linkage with polymorphic genetic markers. The majority of cases cannot be examined by these techniques. Their value and limits are discussed.

The chromosomal assignment of genes responsible for malformation syndromes associated with increased susceptibility to malignancy could be determined owing to specific constitutional chromosomal abnormalities or to family studies. For certain types of tumors, somatic chromosomal rearrangements (loss of alleles) occur at the same locus indicating the presence of a recessive suppressor gene or an antioncogène. For other types of tumors chromosomal rearrangements involving regions different from the locus for predisposition suggest genetic heterogeneity and/or implication of genes for tumor progression. These genes which are also involved in development and regulation of differentiation and cell growth, may undergo a differential genomic imprinting.

Oncogenes are cellular genes altered by different mechanisms in numerous human tumors. Under this modified form, because of their intervention in the cellular division and differentiation phenomenons, they can play a role in the malignant process. Nevertheless, there is no univocal link between an oncogene alteration and one special type of tumour. Moreover, the role of other biological parameters, which can influence the oncogenes action, must be considered to explain the generation of a cancer.

The genetic events which are associated with tumorigenesis concern two classes of genes: proto-oncogenes and anti-oncogenes. The first code for products which take part in the positive control of cellular proliferation; the second code for products which are involved in the negative regulation of cell growth. The identification of genes involved in the genetic predisposition to some cancers can be used in predictive medicine, while the observations on proto-oncogenes are already of prognostic value in some instances. In the future they will lead to new therapeutic approaches.

Current therapeutic protocols for medulloblastoma combining, with surgery, radiation therapy and chemotherapy allow 5-year survival rates of over 50%. However these therapies induce mainly in children long-term adverse effects, which produce a therapeutic dilemma emphasizing the need for reliable prognostic factors in order to adapt the treatment modalities to the degree of the tumor's aggressiveness. Contradictory results have been reported concerning the conventional clinical and histological prognostic factors in medulloblastoma. Recent development and simplification of cell biology technologies could now help in the resolution of this issue. The aim of this review is to present some new prognostic factors available from these advances, and to discuss their potential usefulness in the field of medulloblastoma: The measurement of the proliferative potential of tumors using thymidine analogues such as bromodeoxyuridine (BUdR), or the monoclonal antibody Ki-67 is promising. The flow cytometric determination of D.N.A. content in medulloblastomas appears to show a correlation of diploidy with a worse prognosis than aneuploidy. Modern cytogenetic and molecular biology techniques are permitting the current assessment of amplification and overexpression of oncogenes, or the presence of deletions, as prognostic factors in medulloblastoma. The study of the cellular phenotype and particularly the search for differentiation markers has not yet led to clear-cut results from a prognostic viewpoint, but further advances are to be expected in this field, thanks to the development of more specific monoclonal antibodies. The investigation of the tumoral stroma and metabolism is very promising too. These novel approaches to prognostic factors in medulloblastoma should allow a better classification and management of these tumors in the near future.

We describe two cases of adenocarcinoma of the prostate, which deserve being commented because of the unusual features of their occurrence. These were two stage D2 adenocarcinomas discovered within one year in a father and his son. One of the tumors was identified following hemostatic disorders. Thus three aspects of carcinoma of the prostate are studied: their possible occurrence in younger patients, the paraneoplastic disorders of coagulation, and the familial forms.