The authors report a case of Von Recklinghausen's disease of hereditary origin presenting with maxillo-faciale manifestations. They also discuss the therapeutic indications and consider the psycho-social problems associated with facial dysmorphism.

The authors report a series of 42 cases of cystic hygroma of the fetal neck diagnosed antenatally. Cystic hygroma is one of the signs suggestive of chromosomal or congenital abnormalities that occur very early and are very specific. A diagnosis can be made from the ninth week of amenorrhoea onwards by vaginal ultrasound. 73% of the karyotypes that were obtained were abnormal. The large majority (54% = have Turner's Syndrome, but there are some of the karyotypes that are normal. Our figures correspond with those in the literature. Several factors were analysed to show the influence of this pathology on the prognosis which is overall awful (only 11.5% of infants were born alive an only 7.5% survived). Factors for a good prognosis would be a normal karyotype and the spontaneous resolution of cystic hygroma in the second trimester of the pregnancy. Hydrops is a factor of poor prognosis and it occurs in 60% of cases of cystic hygroma but unfortunately 30% of cases where the karyotype is normal have severe malformations (bone, kidney and digestive tract). The resolution of the cystic hygroma in the second trimester of pregnancy does not exclude an abnormal karyotype or a severe congenital malformation associated with the condition. As cases do recur in the same family there is an indication that a suspicion that the condition can be an autosomic, recessive or even dominant condition. The authors advise that the diagnosis should be made early and thoroughly in order to carry out chorionic villus sampling to determine the karyotype early before the very important sign for abnormality disappears as it may.

We discuss the pathogenicity of the association between neuroblastoma and fetal malformations. It appears to us that the role of certain oncogenes could possibly go further than only activate tumors and play a role in the initiation of the process of fetal malformations.

The authors review the literature concerning chromosomal abnormalities in childhood brain tumors: medulloblastomas, ependymomas, and gliomas of low and high grade. Though these technics require further development, they highlight the role of cytogenetic modification in oncogenesis of brain tumors.

Five to 10% of colorectal carcinomas are obvious inherited familial syndromes. The inherited molecular basis of the predisposition is uniformly present in normal cells of such patients. The identification of the genes underlying cancers, performed with the intent to clone, would first serve as a basis for a pre-symptomatic diagnosis. The APC gene, located on the long arm of chromosome 5, is the only molecular target already identified as involved in the predisposition to familial adenomatous polyposis. Other genes are involved in the progression of sporadic colorectal neoplasias. Their identification would help in the comprehension of colonic carcinogenesis. Molecular analysis of these markers determines improvements in the management of a frequent and most severe disease, in which progress in screening and treatment has been very slow over the past twenty years.

The diagnosis of the so-called "small-round-cell tumours" in children and adolescents is a troublesome problem, particularly in specific forms of the disease or/and in undifferentiated cell proliferations. Under these circumstances the finding of a specific chromosomal abnormality in the tumour cells is invaluable, specially for the diagnosis of Ewing sarcoma and primitive neuroectodermal tumours as well as alveolar rhabdomyosarcoma. The use of cytogenetics, in combination with morphological and immunohistochemical studies to identify cell differentiation markers, is either the only positive diagnostic criterion, or a complementary factor in diagnosis.

Insulin like growth factor I (IGF I) and IGF II have both metabolic and growth promoting properties, both display endocrine and autocrine-paracrine effects. In growth stature disorders without GH deficiency (constitutionally short stature = CSS, pygmy) no IGF I gene deletion was detectable by Southern blotting. In CSS the incidence of RFLP for Hind III located near exon 5 was similar to that in the control population, the incidence of the polymorphic (13 kb) EcoRV (located near exon 1) was significantly lower. Cosegregation analysis of these RFLP in families of CSS were uniformative for IGF I gene, but family linkage studies by others demonstrated co-segragation of the IGF I gene region and hypochondroplasia. In pygmy, DNA amplification around exon 1 and direct sequencing revealed polymorphic sites. One of them is located in the consensus sequence upstream from the translational start site in Eucaryotic mRNA. IGF II RNA messenger hyperexpression was noted in many human tumours with genomic abnormalities: IGF II gene hypomethylation, and loss of allele.

Prognosis of breast tumor patients is not clearly-defined. New marker should be useful. A new field of investigation concerns genetic abnormalities in breast tumors. Oncongene amplification and loss of heterozygosity are the most common alterations. 30% of breast tumors show a loss of heterozygosity on chromosome 3p, where thyroïd hormone receptor, c-erbA-beta is localised. We suggest a potential role for this genetic alteration in breast tumorigenesis.

Cathepsin D, an acidic protease normally acting in lysosomes, is overproduced both in vitro and in vivo in most breast cancer cells. The mechanism of gene regulation by estrogens and the biological and clinical significance of this overexpression in metastasis are reviewed. In MCF7 cells, cathepsin D is specifically and directly induced by estrogens and also induced by growth factors (EGF, IGF-I and bFGF), but this induction is dependent upon de novo protein synthesis. The mechanism of estrogen induction involves EREs located upstream from the gene. Our laboratory cloned the promoter region (-4kb) of cathepsin D of MCF7 cells and found EREs located in the proximal 5' region of the gene. In MDA-MB231 and BT20 cells, cathepsin D is overexpressed but not regulated by estrogens. Total cathepsin D concentration were assayed by IRMA in breast cancer cytosol routinely prepared for receptor assays. Several retrospective clinical studies indicate a significant correlation between high cathepsin D concentrations in the cytosol of primary breast cancer and further development of clinical metastasis. High cathepsin D concentration in the primary tumor may be either a consequence, or more likely a cause, of metastasis. Transfection experiments using cDNA-cathepsin D in rat tumoral cells facilitates their metastatic potential in nude mice (Garcia et al., Oncogene, 1990, 5, 1809-1814). The mechanism of cathepsin D action in facilitating metastasis is unknown and may involve proteolytic activity in an acidic compartment, and/or interaction with the Man 6P/IGFII receptor.

Dysplasia is the only marker for malignant potential in Barrett's esophagus. The histologic interpretation of dysplasia is sometimes difficult, particularly when attempting to distinguish dysplastic changes from those of a regenerating and inflammatory mucosa. In order to find an objective marker to identify patients with high risk of malignant transformation, the authors evaluated 497 biopsies from 66 patients with Barrett's esophagus with flow cytometry. The aim of the study was to correlate DNA content and proliferative abnormalities with histology. All biopsies classified histologically as negative for dysplasia had a diploid DNA content. The percentage of biopsies with an aneuploid DNA content increased with the histologic grade of dysplasia: 2 percent of indefinite dysplasia, 11 percent of low grade dysplasia, 44 percent of high grade dysplasia and 78 percent of biopsy specimens with cancer biopsies were aneuploid. Mean S and G2M fractions of diploid biopsy specimens increased with the severity of histologic changes. The S and G2M fraction threshold values that could differentiate patients that were negative for dysplasia from those with high grade dysplasia or cancer were 9 percent and 6 percent, respectively. Aneuploidy or G2M fraction greater than 6 percent was the best discriminating criteria between those two distinct groups of patients. All 6 patients with high grade dysplasia or cancer had aneuploid cell populations or increased G2M fraction, whereas none of the 35 patients whose biopsies were histologically negative for dysplasia had evidence of genomic instability or increased G2M fraction. Flow cytometric abnormalities were found in 10 out of 25 patients whose biopsies were classified as indefinite for dysplasia or low grade dysplasia.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokine gene expression could be studied by both immunohistochemistry and in situ hybridization. These techniques allowed us to demonstrate the role of IL-6 and IL-2 in the pathophysiology of Castelman's disease and CD25 positive malignant lymphomas, respectively.

In experimental models chemotherapeutic agents enhance spontaneous metastases. Vascular toxicity and myelotoxicity may account for this phenomenon. However, drugs may act directly on tumor cells. Clonogenic resistant cells are involved in the metastatic process facilitation. Fundamental biological mechanisms are evoked to explain these observations. Mutagenicity and its consequences on gene expression or regulation are another hypothesis. Clinical investigations are necessary to confirm the results obtained from animal models.

Two forms of neurofibromatosis are currently described. Von Reckinghausen Neurofibromatosis (NF 1) is the classic and common form, recently localised to chromosome 17. Neurofibromatosis type 2 (NF 2) or bilateral acoustic Neurofibromatosis, formerly the "central form" of von Reckinghausen disease, is characterized by multiple brain tumors, most often bilateral acoustic neuromas. The NF 2 mutation lies on the long arm of chromosome 22. The two forms predispose to benign or malignant familial tumors, derived from neural crest germ lines, such as Schwann cells. Rapid progress in the understanding of mechanisms underlying neurological tumor formation is expected in these inherited diseases. Molecular biology will allow the precise identification of genes responsible for the neurofibromatose syndromes. Practical applications, such as screening of individuals at risk for the disease will soon be available. Medical follow-up and genetic counselling should improve as a result of these advances.

We have investigated the liver-specific expression of IGFBP-1 gene, an Insulin-like Growth Factor binding protein. Northern blot as well as transient transfection experiments, both carried out in differentiated (H4II, C2Rev7) and dedifferentiated (H5, C2) hépatoma cell lines, yielded clear cut data allowing the involvement of HNF1, a liver-specific trans acting factor, in basal IGFBP-1 liver-specific expression.