The retinoblastoma is a rare childhood tumor which occurs in children, 40% of them being diagnosed in an hereditary context. The gene involved in the hereditary predisposition and in the tumoral development was isolated (RB-1) and is of the antioncogene-type. RB-1 mutations were found in many other tumors. The absence of the antioncogene protein expression is responsible for the tumor development and a contrario its presence in normal cells has tumor suppressive properties. This property was demonstrated by phenotype reversion of retinoblastoma or other cell lines (with no RB-1 protein), induced by reintroduction of the gene coding for the normal RB-1 protein. The normal RB-1 protein undergoes multiple phosphorylations during the cell cycle, regulating its activity, the active form being hypophosphorylated. RB-1 is involved in the transcription regulation of many cell cycle genes, and in cell differentiation. Experimental animal models are under investigation, in order to established whether RB-1 overexpression in normal cells will protect them from tumor development, and to plan tumor gene therapy by injection of recombinant viruses allowing RB-1 expression in tumor cells.

The p53 gene is known to play a central role in cancer. In fact, no human tumor type is devoid of p53 mutations, although differences can be seen in the relative frequencies and patterns of nucleotide substitutions. Our work illustrates these differences, since frequencies of mutations ranged from 15 to 80% and the patterns of mutations were distinctly different in skin cancers compared to breast tumors. Furthermore, it is well established that whenever p53 mutations occur during tumor progression, their appearance greatly affects the natural evolution of cancer. This is confirmed by the correlations found between p53 mutations and the negative outcome of the disease in a number of tumor types.

The c-Ha-ras-1 polymorphism was studied in 92 bladder tumor samples (newly diagnosed and/or recurrent) obtained from 73 patients and in the paired white blood cells (WBC). A heterozygous state was detected in WBC DNA of 38 patients (52%). The statistical analysis (univariate and multivariate) demonstrated an association between the heterozygous state of the patients and a lymphatic invasion. In patients with a pTa tumor, there was a relation between the heterozygous state and a younger age at diagnosis. A loss of heterozygosity for c-Ha-ras-1 locus was detected in seven out of the 38 informative tumors (18.4%). No significant correlation was observed with the prognostic factors. These results address the relation between the heterozygous genomic state and the risk of lymphatic invasion in the patients with a bladder tumor.

The course of bladder tumours is difficult to predict. The most reliable prognostic factor at the present time is histological grade. Cytogenetic subclasses of bladder tumours can be distinguished on the basis of the demonstration of karyotype anomalies in bladder tumour cells. Eighteen patients underwent cytogenetic examination of their bladder tumour and were followed for an average of 35 months. Multivariate analysis of the clinical and laboratory parameters studied revealed the importance of age and the absence of trisomy 7 in the tumour on patient survival. The presence of trisomy 7 in a bladder tumour may therefore constitute a factor of poor prognosis. This hypothesis needs to be confirmed by further studies in larger populations. The search for this anomaly can be performed by fluorescent in situ chromosomal hybridisation, a technique which transforms cytogenetics from an experimental procedure into a routine complementary investigation. These techniques can be performed on urine samples, suggesting the possibility of their application to screening or follow-up of bladder tumours.

The early diagnosis of digestive cancer is usually based on the detection of the presence epithelial histological abnormalities known as dysplasia. The histological features described constitute an intermediate step between normal tissue and actual cancer. Two degrees of dysplasia are now distinguished: moderate dysplasia and severe dysplasia (the latter being equivalent to in situ cancer or stage 0 cancer). The difficulty in reliably identifying and classifying dysplasia has led to the development of additional methods able to detect abnormalities of the genetic material, particularly of DNA. The use of flow cytometry to examine tissue makes it possible to analyse the DNA content of the tissue nucleus by nucleus. Normal tissues have a normal DNA content and are described as "diploid". Tumor tissues frequently contain abnormal quantities of DNA and are described as "aneuploid". Pre-cancerous aneuploidism could be identified before cancer develops and detected in dysplastic states. The authors report their own experience and that of many other authors of the value of this additional method of investigating precancerous lesions of the digestive tract.

Precancerous lesions of the bronchial epithelium are dysplasias and in situ carcinomas. Squamous metaplasia has not yet been considered as a true malignant state. Epithelial cells, which are able to proliferate (non terminally differentiated) in bronchial tree and alveoli, are the candidates for malignant proliferation (basal cells, mucus cells, Clara cells and type II pneumonocytes). Their initial growth is probably promoted by deregulated autocrine growth factors (EGF, GRP, IGF1), or their receptors (EGF-R). Under continuous carcinogens exposition these proliferating cells accumulate multiple genetic abnormalities affecting dominant oncogenes such as myc and ras, and recessive tumor suppressor genes such as Rb and p53. Neither the order of intervention of these genetic factors nor their correlation with premalignant states have been demonstrated.