Medullary thyroid cancer (MTC) is either of the sporadic or familial type, whether it be isolated or constitute part of a type II multiple endocrine neoplasia. Progress in the knowledge of the disease has recently been obtained in the following ways: the IRMA assay of mature calcitonin, the disease marker, has permitted earlier diagnosis of familial cases and recurrence; the locus assignment of the gene on chromosome 10 now enables a valid discrimination in certain families of gene carriers; collaborative clinical, biological, pathological, therapeutic and epidemiological research on a nation-wide scale has had a beneficial effect on patients, with improvement in diagnosis of the familial forms, in disease prognosis, in cancer detection at an infraclinical stage, and in the regrouping and distribution of families in France.

Through a family form study and a literature review, the authors define the symptoms of the Gardner's disease and the checkup to be carried out. Sometimes, the surgical treatment, proposed in an aesthetical purpose, is difficult to carry out due to the tumor location and consistency. Incomplete forms are likely to be more frequent but the risk of colic degeneration remains the same as for the usual form. Examination and multi-departmental care are required.

Four cases of tuberous sclerosis in two families are presented. We studied the oral manifestations of the disease and we suggest that dental pits should be taken as clinical markers for diagnosis in oligosymptomatic cases. We found that feature in all patients affected by tuberous sclerosis.

Genetic alterations in solid human tumors occur in several groups of genes, one of which contains the proto-oncogenes. These genes are involved in the control of cell proliferation and become activated in oncogenes by various mechanisms. These activations are reviewed herein.

Correlations have been established between phenotype and karyotype in spontaneously aborted specimens. The criteria used to determine the phenotype were based on estimated developmental age and macroscopic examination of embryo and placenta, taking into account the morphological modifications due to in utero retention. The probability that a chromosomal aberration was the cause of the abortion is high when the developmental arrest occurred before 5-6 weeks and the expulsion was delayed. The frequency could be estimated at 75% when the developmental arrest was at 2-3 weeks, and 65% when the developmental stage reached 5-6 weeks. Main anatomical features are described permitting an attempt to assign the type of chromosomal anomaly by ultrasonographic examination.

Oncogenic cell transformation induces major changes in the structure and physiology of the cells: modifications of morphology, differentiation block, disorganisation of cytoskeleton and extracellular matrix, alterations in growth control. The identification of oncogenes relies upon transfer into host normal cells of DNA isolated from cancer cells. The recent development of DNA transfer into germinal cells has provided new insights into the genetic control of tumorogenesis in vivo. In most cases, full transformation into leukemic or tumor cell requires the cooperation of several oncogenes. These observations support the hypothesis of cancer as a multistep process. However, many of the cooperative oncogenes have not yet been identified, especially in human cancers. The recent discovery of genes acting as repressors of cell growth in normal cells has brought to light a new class of potential recessive oncogenes that might have a contributory function in cancer development.

The biological behaviour of invasive carcinoma of the uterine cervix is not always predictable. It is therefore important to establish new biological markers which could be useful in determining a more reliable prognosis. We have analyzed the c-Ha-ras and c-myc proto-oncogenes in a large series (154 cases) of cervical cancers at various clinical stages. Alterations of c-Ha-ras (deletion, mutation) and c-myc (amplification) were frequently observed in cervical cancers and were shown to be associated with tumor progression. Furthermore, c-myc overexpression, when detected in early cervical cancers, provides a means of identifying patients at high risk of early recurrence.

Twenty-five colorectal tumors (rectum 6, left colon 13, right colon 6) were studied with respect to the overexpression of p53 and the activation by point mutation of the Ki-ras oncogene. Single point mutations on codon 12 and codon 13 were analyzed after PCR amplivication, dotblotting and sequential hybridization with 12 different oligonucleotides. The intranuclear concentration of p53 protein was measured by flow cytometry after immunofluorescence staining with monoclonal antibody Pab 421. Twelve tumors were found to significantly overexpress p53 and 6 of them had an activated Ki-ras (5 on codon 12, 1 on codon 13). Of 13 tumors which failed to demonstrate over expression of p53, 8 had an activated Ki-ras (5 on codon 12, 3 on codon 13). In our series, p53 overexpression and ki-ras activation appeared to be independent.

Over the past ten years there has been fundamental progress in molecular biology, i.e. concerning the structure and function of genes. The understanding and diagnosis of several diseases, in particular those of the respiratory system, have been profoundly affected and changed. For example alpha-1-antitrypsin deficiency and the emphysema which results have now been dissected down to a molecular level and characterised by anomalies of certain critical portions of the gene coding for this protein. The same thing is found in cystic fibrosis where, thanks to recent technical progress, it is now possible to make a positive diagnosis in most unaffected carriers. The importance of molecular biology in lung cancer is equally established, and in small cell lung cancer one can already isolate a sub group of cancers presenting with an abnormal amplification of the c-myc oncogene. Finally, the role of inflammatory cells, in particular macrophages, in pulmonary fibrosis is best understood by studying the expression by macrophages of the genes coding for mediators which alter the replication of fibroblasts.

The authors report the case of a 20-year old male patient presenting with a lateral thoracic tumour which at pathological examination looked like an extra-osseous Ewing's sarcoma. Strongly positive NSE immunolabeling suggested a recently described variant of this lesion: Askin's tumour. In 1979, F. B. Askin described a tumour made of round small cells, located on the side of the thorax and possibly derived from differentiated neuroectodermal tissue. Since that time, the ever wider use of electron microscopy and immunohistochemical methods has made it possible to demonstrate the existence of peripheral neuroectodermal tumours (PNETs) distinct from neuroblastomas. Askin's tumour being only, as it turned out, one of their clinical forms. Following a brief presentation of the clinical, pathological and therapeutic features of PNETs, the authors underline the great similarity between these tumours and Ewing's sarcoma. Owing to the successive discoveries of a cytogenetic abnormality common to these tumour--t(11;22)(q24;q12)--, of a similar expression of proto-oncogens and of identical neuroenzymatic characteristics, Ewing's syndrome can now be regarded as the most undifferentiated of all PNETs, probably arising from the postganglionic neuron of the parasympathetic system.

Recent studies have shown that lung cancer patients frequently suffer inactivation of antioncogenes such as Rb gene (13q14) and p53 gene (17p13). In a study of 48 cases of non-small cell lung cancer (28 squamous-cell carcinomas, 11 adenocarcinomas, 4 large-cell carcinomas, and 5 other types) using restriction fragment length polymorphism analysis, we found DNA sequence deletions from chromosomes 1p32-36, 3p21, 11p15.5, and 11q13. The frequencies of allele loss on chromosome 1p, 3p, 11p and 11q are 31, 57, 20 and 49% of informative cases in this patient group, respectively. Of them, 19 tumors show one allele loss and 10 patients suffer two or more allele losses from different chromosomes.

The growth fraction of cancer cells, estimated by the monoclonal antibody Ki-67 labelling, and DNA content were determined simultaneously en K562 human leukemic cells by flow cytometry. Adriamycin, aclacinomycin A and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreases the fraction of Ki-67 positive cells, Ki-67 negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

The expression of tumor-associated transplantation antigens (TATA) by two metastatic variants, isolated from B16 melanoma in vivo, was examined. The first, YB16 melanoma (amelanotic), was selectioned after a successive s. c. transplantations of B16 melanoma cells on the coisogenic Yellow AY/a mutant mice of C57BL/6J mice. The second, MB16 melanoma, characterized by a variable pigmentation, was obtained from a s. c. transplantation of YB16 melanoma cells on C57BL/6J mice. The comparison of TATA expressed by the two variants and the B16 melanoma, made between different modes of inducing tumor-rejection activity, revealed that i) these two variants failed to induce an autologous antitumor response, ii) they were resistant to crossed immunization with an immunogenic preparations of B16 melanoma and iii) only MB16 melanoma preparations reduced significantly the tumoral incidence of B16 melanoma cells. These data leads us to suggest i) that the s. c. transplantation of B16 melanoma cells on Yellow AY/a mice resulted in the selection of nonimmunogenic, amelanotic and metastatic cell population of YB16 melanoma and ii) the existence of an epigenetic regulation of melanogenesis and expression of TATA in MB16 melanoma cells carried on C57BL/6J mice.

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis--this stiffening up limite, rather than accentuates, the value and reproduction potential of a stud bull past prime. But associated with these abnormalities--and not seen in age-matched cows of comparable breeds--are fascinating endocrine neoplasms that might suggest a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies, that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C-cells" of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma--in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy.(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro models with multiple drug resistance (MDR) phenotype have been frequently related to hyperproduction of the 170 kd membrane glycoprotein, the so-called 170 GP. This protein is a pump able to extrude from cytoplasm drugs with various structures and mechanisms such as doxorubicin (DXR) or vinblastin (VLB). The MDR1 gene encodes the GP 170. MDR1 gene expression is low in most of the normal tissues, but high in some tissues such as colon, kidney, or liver. In these tissues, the GP 170 would ensure a detoxifying function related to cellular toxic compounds. There is a broad range of MDR1 gene expression in human tumors as a result of several factors. Of particular importance are the tissue origin from which the cancer derives and previous chemotherapy. In some cancers which often exhibit acquired chemoresistance, such as non Hodgkin's lymphomas, leukemias, sarcomas or neuroblastomas, an increase of MDR1 gene expression following previous chemotherapy has been frequently observed. Moreover in these cancers, a relationship between MDR1 transcript levels and clinical response to chemotherapy could exist as shown in several studies including one of ours. Hematosarcoma in the adult and some pediatric cancers seem to be models in which MDR1 gene expression may have a clinical relevance. Thus, an increase of MDR1 gene expression during the course of chemotherapy would lead the clinician to choose "non MDR related" agents such as DXR, VLB; or to use agents that are able to reverse MDR phenotype.