The "Groupe d'Etude des Néoplasies Endocriniennes Multiples de type 1 (GENEM 1)" is a French group involved in a comprehensive multicentre study of Multiple Endocrine Neoplasia type 1 syndrome (NEM 1). The objectives of this group are to define diagnostic and therapeutic protocols and to carry out genetic research on NEM1. The first aim of physicians is to recognize the syndrome and to determine the appropriate screening especially into two circumstances: 1 degree In case of isolated and sporadic glandular disease -i-e-parathyroid glands, endocrine pancreas, antehypophysis, adrenal glands and neuroendocrine tumors? 2 degrees In case of very high probability of NEM 1 syndrome? This paper answers these two questions, based on the analysis of the first 150 cases collected by the GENEM 1.

Carcinogenesis is a multigenic phenomenon where 3 prevailing types of genes are involved: oncogenes which stimulate the cell proliferation, tumor suppressor genes which act as inhibitors and metastagenes which contribute to the tumor progress. In animal models it has been shown that epithelial skin carcinogenesis proceeds stepwise: initiation, promotion, premalignant progression and finally malignant conversion. The oncogene c-H-ras and the tumor suppressor gene P53 are the genes whose involvement in these steps of epithelial skin cancers are duly established. Less experimental data are available concerning melanoma. the role of the oncogene N-ras, the tumor suppressor gene MTS-1 (encoding for protein p16) ans the metastagene nm 23 has recently be emphasized. Some cytogenetic abnormalities on chromosomes 1, 6, 9, 10, 11 and 17 have also been observed and incite to look for other genes potentially involved in the development of this tumor.

Various gene systems are involved in events occurring during transformation of a normal cell into a cancer cell. By order of intervention, genes responsible for an increased individual susceptibility to cancer can be distinguished from actual cancer genes, followed by genes involved at other levels of carcinogenesis. 15 to 20% of patients with breast cancer have a first-degree relative affected by the same cancer, although an inherited predisposition to cancer is only established in 4 to 10% of cases. The genetic heterogeneity of familial forms of breast cancer make it difficult to identify susceptibility genes. At the present time, 3 regions of the genome have been implicated in the predisposition to breast cancer in women: the BRCA1 gene, the BRCA2 gene and the TP53 gene. All predisposition genes are able to transmit susceptibility due to a mutation or inherited microdeletion.

For the past decade, primary chemotherapy has been extensively used in breast cancer treatment. However, valuable indicators of tumor response are needed. Fine-needle cytopuncture allows the study of malignant cells by cytologic examination, image analysis and flow cytometry. Some parameters evaluated before treatment (cytologic grade, nuclear area and S phase) or at the beginning of treatment (cytomorphologic and cell kinetic changes) have been shown to be correlated with tumor response. The methods, their value and limitations, and results of the literature are discussed.

It is shown that breast cancer can be considered as a paradigm of comprehensive cancer biology and treatment based on analysis of each individual tumor. Historically, it was first observed in breast cancer that tumor progression could be dependent on factors regulating physiological activities (i.e. hormones). It was also observed that tumor growth progressively becomes autonomous, through successive degradation of the multiple steps involved in the control of cell proliferation and differentiated activities. Hormonal treatment of breast cancer provided the first example of targetted biotherapy. The discovery of the mechanism of action of hormones via specific receptors opened the field of tumor tissue analysis to determine the main biological factors involved in tumor progression. In the near future, such data should be the best guide for selection of the most appropriate treatment in each individual case.

The authors studied DNA content in a case of small cell carcinoma with hypercalcemia. This tumor exhibited typical clinical, histological, immuno-histochemical, ultrastructural and biological patterns. DNA content was measured both by flow and image cytometry performed on unfixed tumoral samples. The proliferation index was 10%. These results are similar to those of the literature obtained retrospectively from 10% formalin fixed tissues. The DNA content is a clue to distinguish this entity from other small cell carcinomas of the ovary because immunohistochemical findings are not always informative. The diagnosis of small cell carcinoma of hypercalcemic type should be questioned if DNA content is abnormal.

The purpose of this review is to study the literature concerning normal colon and colorectal cancer for evidencing that the location of the primary proximal or distal tumor may determine two categories of carcinogenesis. The proximal or distal normal colon can be considered as two different organs. Their embryologic origins are different, the splenic flexure starts the distal segment. Antigenic pattern as well as the use of metabolic pathways, such as that of glucose, butyrate and polyamines differ. Epidemiologic, macroscopic and histological features and the inherited and acquired genetic abnormalities allow in some cases to distinguish between two types of cancer according to their proximal or distal location. These two forms are not entirely different and these features can overlap. However the recognition of these two different forms of colon cancer, must be taken in account for clinical or basic research and evaluation of data.

Cell cycle progression is regulated by the sequential activation of cyclins expression and their association to the cyclin dependent kinases (CDK). Several in vitro and in vivo studies indicate that inappropriate cyclin expression (cyclins D, E, A) in the cell, whether or not due to chromosomal rearrangements, can participate in cell transformation. Thus these studies implicate cyclins in human carcinogenesis.

A biphasic synovial sarcoma occurring in the anterior and inferior mediastinum in a 19-year-old woman is reported. A biopsy showed a mesenchymal proliferation and the tumor was first misdiagnosed as a hemangiopericytoma. Inefficacy of chemotherapy led to a tumorectomy. Histologic and immunohistochemical studies on multiple samples showed a biphasic tumor. Ultrastructural study confirmed the presence of epithelial elements and cytogenetic analysis disclosed a translocation t(X;18) (p11;q11), leading to a diagnosis of synovial sarcoma. Synovial sarcoma of the mediastinum is very rare and to our knowledge has not been previously studied with the help of cytogenetics. Given the biphasic pattern of the tumor and its mediastinal location, it can be confused with mesothelioma. This stresses the interest of chromosome analysis in the study of tumors histologically difficult to classify.

Most chemical carcinogens are not by themselves reactive. They are in fact procarcinogens and, before becoming toxic, they must undergo some metabolic transformations, directed by enzymatic systems under genetic control. Because of this system of defence, xenobiotics undergo in vivo a more or less sophisticated metabolic process that usually involved at least two phases: after activation phase (or "functionalization"), then a conjugation phase that allows elimination of the processed molecule. The initial step is in most cases on oxidation by P450 cytochroms. The conjugation step may involve a molecule of sulfate (sulfotransferase), of glucuronate (glucuronyltransferase) or of glutathione (glutathione-S-transferase). In man, large interindividual variations in the the expression in these enzymes have been demonstrated, probably depending on a genetic polymorphism. They are responsible for variations in individual susceptibility to carcinogens.

The authors determined the desoxyribonucleic acid (DNA) content of 45 small-cell lung cancers, by flow-cytometry (FC), from bronchial brushings to asses the prognostic meaning of the DNA index, the percentage of cells in DNA synthesis phase (% S) and the ploidy. Moreover, the value of this tumorous cells brushing was assessed for Flow-cytometric analysis. Bronchial brushing offers some advantages opposite to biopsies, but the low quantity of collected cells reduces the number of tumors analysable by FC. The output is low (39%) for determination of DNA index, and moreover low (22%) for determination of % S. In regard to the flow-cytometry analysis, the DNA content does not show any significant difference of survival where as the % S is related to survival, but it seems to be paradoxical in this study. Indeed, patients with small-cell lung cancer associated to high cells' percentage in DNA synthesis phase have the longest survival.

Ovarian carcinomas constitute the major cause of the mortality and morbidity in gynaecology. Most ovary carcinomas are epithelial tumours. Our understanding of ovarian cancerogenesis has been hampered by the lack of a well defined precursor lesion, the lack of knowledge about tumour progression, and by the relative inaccessibility of the ovaries in the abdominal cavity. Recent studies using experimental models allow us to better define the fundamental mechanisms of carcinogenesis from the serous ovarian cells and of invasion of the abdominopelvic cavity by proximity. This review article tries to update on epidemiology, genetic syndromes, biology, screening, and therapy of these epithelial tumours, and about the new directions taken by basic and clinical research. We will present data concerning oncogenes and tumour suppressor genes involved in epithelial ovarian tumours, regulation of tumour cells by growth factors, genes involved in tumour invasion, and mechanisms used by the cancer cell to resist to therapies. Non-epithelial ovarian tumours will not be examined in this manuscript.