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.

The etiology of breast cancer is a complex interplay of various factors, including genetic alterations. A number of studies have been made to identify and characterize mutations that frequently occur during breast tumorigenesis. In this paper, we have described a new deletion, located on the long arm of chromosome 7. Patients whose tumor carried a deletion on chromosome 7q had a significantly shorter survival time. These findings identify the long arm of chromosome 7 as a candidate region for a putative tumor (or metastasis) suppressor gene.

Ataxia telangiectasia (AT) is a hereditary disease transmitted in a recessive mode and characterized by chromosomal instability and radiosensitivity. AT patients have a 100-fold higher risk of cancer than the general population. Although AT is a rare disease of which the frequency has been estimated to be 1/40,000, the frequency of the heterozygosity status, when assessed with the Hardy-Weinberg equation is high (about 1.4%). Parents of AT children, thus obligate AT carriers, show chromosomal instability and radiosensitivity, but at a lower level than AT patients. Assuming that these AT characteristics deal with the cancer predisposition, it can be hypothesized that AT heterozygote individuals have a higher cancer susceptibility than the general population. To test this hypothesis, M Swift's group compared cancer incidence rates from adult blood relatives of AT patients with controls. The risk of cancer in AT heterozygotes could be increased by 3.5 and, for carrier women, the breast cancer risk could be increased by 5.1. Actually, the diagnosis of the AT heterozygote status is not possible. However, the near cloning of the gene (or genes) for the disease will permit to identify the AT carriers in a population of patients suffering from cancer and to assess precisely the impact of AT heterozygosity in the genetic predisposition to cancer.

The HuIFN-alpha and beta genes were examined by the PCR method in the 11 human lymphoblastoid cell lines. The results showed that the homozygous deletion of HuIFN-alpha and beta genes was detected in 5 of 11 cell lines and in 5 of 11 cell lines, respectively. The deletions of both the HuIFN-alpha and beta genes were observed in 4 of 11 cell lines. One T cell leukemia cell line deleted only HuIFN-alpha gene, while the other T cell leukemia line deleted only HuIFN-beta gene. This suggests that the deletions of HuIFN-alpha and beta genes may be related the development of leukemia or lymphoma.