The diagnostic and prognostic value of the DNA ploidy level (nuclear DNA content) was studied in a series of 847 tumours of the nervous system. This series included 93 nerve sheath tumours, 224 meningiomas, 389 neuro-epithelial tissue tumours, 46 primitive neuroectodermal tumours (retinoblastomas, medulloblastomas, neuroblastomas, etc.) and 95 brain metastases. The DNA ploidy level determination was carried out by means of the computer-assisted microscope analysis (digital cell image analysis) of Feulgen-stained nuclei. The results show that the DNA ploidy level does not contribute significant diagnostic information when tumours are analyzed individually. Indeed, some tumours which are definitely benign like certain schwannomas and meningiomas can exhibit very high levels of aneuploidy, while some highly malignant tumours like certain glioblastomas and neuroblastomas can be diploid. In contrast to its weak diagnostic value, the DNA ploidy level appears to be a powerful prognostic factor with respect to the supratentorial astrocytic tumours of the adult. Indeed, patients with hypertriploid astrocytic tumours exhibit a survival period which is significantly longer when compared to that of patients with non-hypertriploid astrocytic tumours. These hypertriploid astrocytic tumours could be involved in a process of biological degeneration when reference is made to their proliferation activity which is significantly weaker than that of non-hypertriploid tumours.

Molecular biology has produced important achievements in research, and provides useful applications to the clinical field. This is true today in diagnostics, and will be true in therapeutics tomorrow. The identification of pathogenic mutations through direct analysis of known genes allows diagnoses to be reached in a growing number of disorders. When mutations cannot be identified, familial linkage studies using polymorphic molecular markers will reach a diagnosis indirectly, most of the times. This is useful either presymptomatically or prenatally. The identification of genetic risk factors in targeted populations is becoming a means of prevention of multifactorial diseases. This approach opens a very large field of applications of molecular genetics in clinical practice. Basic concepts of molecular genetics are briefly reviewed, and the principles of diagnostics in hereditary diseases are approached via a few representative examples.

During the last decades, major medical advances have been made in the understanding of cancer biology and led to the appearance of new diagnostic tools and development of innovative therapeutics. Some basic concepts in molecular medicine, oncogenes and tumour-suppressor genes are reviewed. Special topics are devoted to Ras, erbB2, p 53 and characteristical gene rearrangements, such as bcr-abl, RARA-PML, VDJ, bcl2-IgH. The greater knowledge of the molecular etiology of cancer will contribute to disease screening, diagnosis, staging and therapy, detection of residual or recurrent disease, and development of new treatments, such as gene therapy or drugs targeted to oncogene products.

Familial uveal melanoma are rare and a few number of cases has been described in literature until now. An autosomal dominant inheritance was proposed.

In 40% retinoblastoma (Rb) results from a hereditary mutation of the Rb susceptibility gene (RB1). In this study, we tested the usefulness of intragenic DNA analysis for ophthalmologic follow-up in affected families.

364 eyes from 230 patients with retinoblastoma diagnosed and treated at the Lausanne University Eye Clinic from 1964 to June 1994 were retrospectively analyzed with respect to the risk of developing new tumour foci following initial therapy. Among them, 119 eyes from 90 hereditary affected patients were included, consisting of 86 bilateral cases and 4 unilateral cases. The mean follow-up was 65.5 months (5.5 years). A total of 46 new retinal tumours were detected in 21 patients. These new tumours had a size less than 1 disc diameter in 75% and were peripherally located in 78% of the cases, with a statistically significant preference for the horizontal meridians. No new tumours developed in the macular area. 50% appeared in children younger than 1 year and 80% before 2 years of age. 50% of the eyes with recurrences developed new tumours before 7.5 months following diagnosis, and 75% before 14 months. All patients showing recurrences did so before the age of 4.5.

In Barrett's oesophagus, the risk of malignancy is evaluated histologically with the presence of dysplasia. The abnormal expression of p53 protein could represent a useful new marker. The aim of this study was evaluate the abnormal expression of p53 protein in a series of 52 oesophagectomy specimens with Barrett's oesophagus, either non-dysplastic (n = 3), dysplastic (n = 8), or malignant (n = 41). The immunohistochemical study was made on deparaffinized sections with the monoclonal anti-p53 antibody DO7.

The purpose of this study was to determine the prognostic value of the expression of protein p53, EGF receptors (EGR-R), cell proliferation antigen (Ki67) and DNA analysis by flow cytometry on per-endoscopic biopsies as well as the ability of these factors to predict response to concomitant chemoradiation in patients with squamous cell oesophageal carcinoma.

Multiple endocrine neoplasia (MEN) is a group of characteristic affections involving benign or malignant secreting tumours of several endocrine glands. Recent progress in genetic mapping has led to the precise localization of the genes causing these familial diseases. This technique provides new means of diagnosis greatly improving conventional diagnostic methods. In type 1 MEN, laboratory tests are directed to identifying the target gland and its effect on hormone status. Imaging techniques including echography, CT scan, magnetic resonance imaging, echoendoscopy and scintigraphy add further information. The molecular genetics approach is an indirect one based on a family study. Blood samples must be obtained from at least two certain probands and at least two healthy members of the family. By mapping the genes with precise genetic probes, the morbid haplotype could be identified and used to predict the risk of morbidity in the descendance. The GENEM 1 (Groupe d'Etudes sur les Néoplasies endocriniennes multiples de type 1) is a multidisciplinary collaboration between endocrine surgeons, endocrinologists, gastroenterologists, geneticians, pathologists and biologists working towards identifying the causal gene and better understand the pathophysiology of these tumours. We are undoubtedly on the threshold of this discovery which could help improve the diagnosis of this generally poorly recognized disease with an underestimated prevalence.

Allogenic bone marrow transplantation is widely used to treat many diseases of the haemopoietic system as well as metabolic disorders. Follow-up is essential to assess acceptance, rejection or post-graft relapse. This study was undertaken to evaluate the usefulness of the minisatellite probes MS31 and MS43 used as a routine follow-up test after bone marrow transplantation.

Specific and recurring chromosomal and genetic alterations have been identified in gliomas and could described a model of tumoral progression from benin glioma to glioblastoma multiforme. However, the heterogeneity of profiles of molecular alterations that have been observed in gliomas seems to reflect the variety of clinical evolutions which characterise those tumors. Loss of genetic material on chromosomes 17, 9 and 19, then of chromosome 10 have been associated to pathogenesis of glioma and a pejorative prognostic value have been attributed to the alteration of chromosome 10. Gliomas also express growth factors and growth factors receptors that may be important in promoting tumor growth, like Epidermal growth factor (EGF), fibroblast growth factors (FGF) and vascular endothelial growth factor (VEGF). Tumoral invasion which characterise also gliomas, may involve proteases like plasminogen activators (PA) and metalloproteases, under the regulation of specific receptors and inhibitors. PA inhibitor type 1 (PAI1), associated to the most aggressive form of gliomas, may also participate to tumoral neoangiogenesis. Description and understanding of these alterations may contribute to develop new treatment modalities in gliomas.

The p53 gene, located on chromosome 17p 13.1 and coding for a nuclear 393 amino-acids phosphoprotein acts to constrain or antagonize cell growth, and as such, is a tumor suppressor gene. In fact, inactivation of p53 tumor suppressor gene is a common event in the development of all or most types of human cancers. About half of cell cancer cases analysed thus far involve missense mutation of one p53 allele combined with the deletion of the second allele, and many of the remaining cases involve a functional inactivation of p53 protein through non mutational mechanisms. The importance of p53 as an inherited cancer susceptibility gene has been demonstrated in Li-Fraumeni syndrome. In some circumstances, it has been shown that in response to DNA damage, the p53 level in the cell increases considerably and induces a cell growth arrest late in G1 phase. This cycle arrest allows the altered DNA to be repaired before entry of the cell into S phase. This function of p53 helps to insure the genomic stability of the cell. Mutations in p53 eliminate this response and result in enhanced frequency of genomic rearrangements. In other circumstances wild type p53 may act by triggering cell death by apoptosis. The p53 protein exerts its physiological functions through various biochemical activities. These include its ability to be a site-specific transcriptional transactivator as well as a repressor of transcription. The oncoproteins derived from several oncogenic DNA viruses including SV40 large T antigen, the adenovirus E1B protein, and papillomavirus E6 protein, as well as specific cellular gene products e.g. mdm2 form complexes with the p53 protein, causing its inactivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer genes can be ranged in three families: oncogenes, stimulating cell divisions; antioncogenes, blocking cell division; anti-apoptotic genes, blocking programmed cell death. Tumor progression usually results from cooperation between modifications of genes belonging to these different families. The familial predispositions to cancer are most frequently due to mutations of antioncogenes or of repair genes; in this later case, the original mutation results in abnormal DNA repair, then in accumulation of somatic mutations which could involve cancer genes. Recently, genes predisposing to familial forms of breast and colon cancers have been identified. Knowledge of such genes leads to possible presymptomatic prediction of the disease, but the preventive possibilities seem to be limited, today, to a preventive surgical exeresis. In the future, it would be desirable that elucidation of the mechanisms of cancer predisposition leads to less aggressive preventive or curative treatments.