Systematic investigation of families of children suffering from retinoblastoma reveals more and more cases of retinoma or phthisis bulbi, cases which used to be called "spontaneous regression". Between 1975 and 1991, we have in this way discovered 11 cases (7%) certain to be carrying retinoma or phthisis bulbi, and a further 5 cases where the same diagnosis is highly probable. Of the 11 certain cases, 5 are unilateral, 6 bilateral, and 8 present family history of the disease. Of the total number of 17 eyes, 16 present retinoma, 1 phthisis bulbi. On clinical examination, all (100%) showed characteristic lesions in the form of greyish homogenous elevated masses in the vitreous cavity. 11 presented calcifications (69%) and in 14 disturbance of the pigment epithelium occurred (87%). The average follow-up is 4 years. Of the 11 patients, 8 are of procreating age and have up to now 25 offsprings. Amongst these, 15 have retinoblastoma (60%), 2 retinoma and phthisis bulbi (8%). All except one of the retinoblastoma cases are bilateral. This study would appear to show that retinoma occurs with a higher frequency than that which is usually given. The figures show clearly that retinoblastoma and retinoma derive from the same genetic disturbances, possibly at different times during cell maturation, and consequently require the same investigation and follow-up.

The presence of an haematological cytogenetic laboratory into a clinical unit allowed to realize a close collaboration between clinicians and cytogeneticists, and to achieve a maximal exploitation of the results of the bone marrow cytogenetic studies in some haematological malignancies. It made it possible to perform sequential bone marrow karyotypes studies during the different phases of a disease: We could thus establish: The diagnostic value of cytogenetic findings for chronic myelocytic leukaemia, secondary acute leukaemia, but not for dysglobulinemias. The prognostic value of cytogenetic abnormalities in chronic myelocytic leukaemia where additional abnormalities to the Ph1 are a hallmark of blastic transformation; in primitive dysmyelopoiesis where they represent a bad prognostic factor; in dysglobulinemias, where they are a signal of terminal evolution. In all these diseases, only complex and multiple abnormalities have a prognostic significance pointing out the emergence of a malignant clone, where as rare and single abnormalities are of no significance. Nowadays, haematological cytogenetic must be bound to molecular biology.

Epidemiological studies indicate that environmental factors are more important for cancer development than inherited factors. However, clinical observations such as familial cancer clustering, constitute compelling evidence to the existence of inherited susceptibility to cancer. Few cancer-predisposing genes have been identified so far, by hard laboratory work and with the help of molecular biology tools. The predisposing genes that have been cloned can be used for DNA-based diagnosis. Genes inherited in altered form in familial cancers are the same genes that are altered in somatic cells of individuals with sporadic cancers. Identification of cancer genes through the study of rare families in which susceptibility to cancer is inherited, could have important consequences for diagnosis and treatment of common cancers.

Despite its rarity, medullary thyroid carcinoma which is hereditary in a quarter of cases and often associated with multiple endocrine neoplasia 2a and 2b syndromes, avises much interest which has lead to the formation of a French multidisciplinary group for the study of calcitonin tumors. This collaboration has resulted in the establishment of a national register and has broadened the knowledge of all specialists concerned. Consequently diagnostic methods are improved, becoming quicker, more reliable and also more thorough due to the setting up of therapeutic protocols. An immunocytochemical staining for calcitonin allows a preoperative diagnosis, providing optimal therapeutic conditions for the patients, especially systematic research of pheochromocytoma and management by a specialized team. Total thyroidectomy and careful lymph node dissection are recommended for all cases. Such progress significantly modifies the prognosis of the disease. Family screening, using plasma calcitonin and, in the near future, genetic studies will hopefully enable the identification of abnormal gene carriers before the clinical stage, thus making total recovery possible.

The trophoblast of early placenta has many attributes of malignant tissue: it displays highly proliferative and invasive properties and expresses hormones, growth factors, growth factor receptors and oncogene products. Moreover, this tissue may have an autocrine control of growth. Collectively, these properties are similar to those of malignant tissues and the normal trophoblast is then considered as a "pseudomalignant" tissue. Moreover, either benign (hydatidiform mole) or malignant (choriocarcinoma) trophoblastic disease may be developed from the trophoblastic cells. In this article, the biological features of both the normal and the tumoral trophoblast will be presented. Finally, the trophoblast is a model and a source of molecules of biological interest.

We report the association of a cutaneous lesion with multiple endocrine neoplasia type 2A (MEN 2A) in three patients from a French family. These lesions are very similar to those previously described in an Italian and an American MEN 2A family and called cutaneous lichen amyloidosis. In all three families the patients presented with a pruritic and pigmented cutaneous lesion localized unilaterally on the upper back. However, in the French family the patients also complained of paroxysmal pain in the same area, in which we could elicit a touch hypoesthesia and pain hyperesthesia. Such an association of cutaneous and neurological features in the upper back is known as Notalgia Paresthetica (NP). NP is believed to represent a neuropathy of the posterior dorsal nerve rami. Unlike the two previously reported families, the histological, immunohistochemical and ultrastructural analysis of the skin biopsies of the French patients did not show any amyloid material. This suggests that the presence of amyloid may not be a constant feature of the cutaneous lesions associated with MEN 2A. We consider these lesions as a form of dorsal neuropathy rather than a cutaneous lichen amyloidosis. Whatever their origin, these cutaneous lesion usually precede the appearance of the neoplastic lesions of MEN 2A. They may act as an early clinical marker that must be searched for in each subject at risk for MEN 2A. In addition, all patients presenting with NP should be screened for MEN 2A.

New powerful techniques capable of effective genome analysis are now available for the study of inherited skin disorders. In most instances, a biochemical defect in the patient points to the responsibility of a given gene in the occurrence of the disease. The role of this candidate gene is tested by genetic linkage studies, then confirmed by identification of the molecular gene defect and collection of evidence that this gene defect is causally related to the disease phenotype. This conventional genetic approach has succeeded in identifying the genes and molecular defects responsible for X-linked ichthyosis, epidermolysis bullosa simplex of Koebner and Dowling-Meara, albinism and piebaldism. When no biochemical clue is available, reverse genetics can be used to delineate the region of the genome that contains the disease locus, thus shortening the search for the candidate gene. This approach, occasionally aided by the presence of cytogenetic anomalies, has allowed to locate and identify the gene for Von Recklinghausen neurofibromatosis (NF1) and to demonstrate the existence of two loci genetically related to tuberous sclerosis.

Cell growth is controlled by two types of genes, i.e., activating genes (oncogenes) and negative regulator genes (antioncogenes). Studies have shown that malignant transformation of a cell can result from either increased oncogene activity or decreased antioncogene activity. Current knowledge of genes relevant to dermatology is discussed.

DNA-repair is a complex enzymatic process which enables all living cells to withstand the deleterious and mutagenic effects of most genotoxic agents. Defective DNA-repair is caused by mutations involving genes which encode the enzymes responsible for recognition and excision of DNA lesions. Some of these genes have been identified in humans. Several severe human diseases are caused by defective DNA repair affecting the entire genome (e.g. xeroderma pigmentosum and trichotiodystrophy) or only actively transcribed genes (Cockayne's syndrome). Some of these conditions are associated with extremely high rate of cancer.

Flow cytometric DNA analysis was performed in 35 patients with squamous cell carcinoma of the esophagus. The aim of this study was a) to establish a tumoral DNA pattern, b) to determine an objective parameter correlating with tumoral response to chemotherapy (5 FU-cisplatin). DNA analysis was performed in perendoscopic ranged tumoral biopsy specimens to determine the DNA ploidy (DNA index) and S phase fraction. Tumor diameter and length were evaluated by computed tomography (CT) before and after chemotherapy in 24 patients. The relative variation of this product determined a CT index. Before chemotherapy, 82 percent (76/93) of the specimens were available for assessment; 72 percent (26/36) of the tumors were aneuploid. In these tumors, the DNA index ranged from 1.23 to 2.80. Five tumors had two distinct and simultaneous aneuploid populations. CT index values were not significantly different according to the ploidy (diploid, aneuploid), the S phase fraction (low, high), the DNA content modification after chemotherapy (absent, present). In this study, DNA analysis did not allow to select patients with higher response to chemotherapy. The inter- and intratumoral phenotypic heterogeneity may be one of the responsible factors.

The authors report a case of hygroma colli, diagnosed in utero by ultrasonography, in Africa, at the Brazzaville (Congo) Teaching Hospital. The ultrasonographic appearances as well as the differential diagnostic aspects of hygroma colli are defined. Because of the frequent association with chromosomal aberrations, the authors suggest the termination of pregnancy in an African context, since karyotyping is not possible in that part of the world.

There are many genetic abnormalities in colorectal cancers, and they can schematically be studied according to 3 approaches. 1. The quantitative abnormalities of the DNA content of the nucleus and the cell cycle are studied with flow cytometry. 2. Karyotypic abnormalities relating to the loss and/or gain of chromosomes or structural abnormalities are studied by cytogenetics. 3. Oncogene or anti-oncogene mutations carried out by these chromosomal segments are studied by molecular biology. When compared to the clinical data, some of these abnormalities have a prognostic value. They allow an insight into the fundamental mechanisms of colorectal carcinogenesis. Finally, they may allow predicting and assessing the efficacy of some adjunctive therapies, especially that of medication.

The purpose of this study was to assess the effects of a somatostatin analog (SMS 201-995), in vitro and in vivo on mice colonic adenocarcinoma cells CT 26. To perform the in vitro study 50,000 neoplasic cells were grown in RPMI 1640 culture medium with different concentrations of SMS and DNA synthesis determination was made. For the in vivo study, 100,000 cells in balb C mice were implanted. Several doses of SMS (200 micrograms/kg/12 h and 100 micrograms/kg/12 h) were given. The weight, size and DNA content of the tumors was determined. No in vitro effect of SMS was demonstrated. Nevertheless, an in vivo inhibition was found for all the parameters studied. A confirmation of these results in other cell lines could point towards possible hormonal manipulation in the treatment of colonic cancer.

We report two cases of Peutz-Jeghers syndrome who underwent intraoperative enteroscopy. In the first case, the fiberscope was sterilized with ethylene oxide, while in the second, an electronic colonoscope was decontaminated with glutaraldehyde plus phenate. The endoscope was introduced through an enterotomy. This led to the discovery of several hamartoma greater than 10 mm which had gone undetected by the surgeon and guided the surgical procedure. In a case with approximately 30 hamartoma, associated endoscopic polypectomy and surgical removal of polyps by eversing the mucosa through enterotomies allowed the medicosurgical team to obtain a "clean small bowel" without resection.

Flow cytometry was used to examine the spatial distribution of nuclear DNA content in Barrett's mucosa, in one patient with high grade dysplasia and in 6 patients with Barrett's adenocarcinoma. All tumors were aneuploid. Each adenocarcinoma but the most advanced seemed to arise from a single clone of aneuploid or near-tetraploid cells which was found in all biopsy specimens taken from the tumor. Multiple aneuploid populations of cells were seen in the larger tumors. Eight clones were individualized in the most advanced case of cancer. In all patients with carcinoma, the mucosa surrounding the tumor was aneuploid. Some areas were characterized by the same DNA index as in the tumor, others contained distinct aneuploid cell populations. The spatial distributions of aneuploid clones and dysplastic areas were not perfectly superimposed. These data suggest that neoplastic progression in Barrett's esophagus is associated with genomic instability preceding the development of malignancy. Clonal heterogeneity in Barrett's adenocarcinoma is more marked when compared to other tumors and suggests a majoration of genomic instability during tumor progression.