DNA nuclear ploidy determined by flow cytometry was evaluated from prostate tissue in 51 patients with prostatic cancer who had undergone radical prostatectomy. DNA ploidy pattern was diploid in 46% and aneuploid in 54% of tumors. DNA ploidy was compared to histological tumor grading. 92 Aneuploidy was found in 0% of the tumors with Gleason score between 2 and 4 in 62% between 5 and 7 and in 50% between 8 and 10. Our results suggest there is no relationship between the two parameters.

Multiple endocrine neoplasia type 2 (MEN 2) is transmitted as an autosomal dominant trait, with 3 different forms. MEN 2a consists of medullary thyroid carcinoma, phaeochromocytoma(s) and hyperparathyroidism. In MEN 2b, parathyroid hyperplasia is absent, but a Marfan-like syndrome and neuromas of the mucosae are present. In some families, the only manifestation of MEN 2 is a medullary thyroid carcinoma. These 3 forms seem to related to one or several gene(s) located in the pericentromeric region of chromosome 10. The histological lesions of MEN 2a are multifocal, bilateral and associated with hyperplasia (which affects C-cells in the thyroid gland). Screening for familial medullary thyroid carcinoma is based upon plasma calcitonin levels measured before and after a pentagastrin stimulation test. The demonstration of DNA markers near the gene(s) of the disease in chromosome 10 pericentromeric region makes it possible to identify, with good probability, the subjects at risk for the disease. It is only by determining the responsible gene(s) that subjects carrying the hereditary anomaly will be identified directly, without marker assays.

The Ki-67 antigen is a cell cycle and tumor growth marker, which can be readily detected using immunocytochemistry methods. Ki-67 antigen is present only in the nuclei of cycling cells and is variably expressed as the cell goes through the various phases of the cycle: both the amount and the topographic distribution of Ki-67 antigen vary in a manner which is sufficiently specific to establish the precise cycle phase for each member of a cell population. From G1 through mitosis, the amount of Ki-67 antigen increases steadily: location of the antigen is nucleolar during G1 and both nucleolar and karyoplasmic during G2. The Ki-67 antigen is widely used to estimate the growth fraction of a tumor cell population; in many malignancies, the percentage of Ki-67-positive cells is correlated with parameters reflecting tumor aggressiveness or progression. These findings demonstrate the potential value of the Ki-67 antigen for the cytopathological or histopathological study of tumors, although neither its biochemical structure nor its function have been fully elucidated to date.

The development of necrosis and macrophage infiltration increases the risk of renal graft rejection. But the macrophages secrete the alpha form of the tumour necrosing factor (TNF) which is also involved in several immunologic and inflammatory phenomena. We therefore studied the expression of the gene TNF alpha by in situ hybridization during advanced stage rejection after renal transplantation: the grafts were infiltrated with macrophage-like cells expressing the mRNA of the TNF alpha gene, particularly deep in the cortex and in the medulla. These cells then secrete the TNF alpha molecule since they are recognized by anti-TNF alpha antibodies. These antibodies also recognize certain other glomerular endothelial and tubular epithelial cells which do not express the TNF alpha gene: these cells are undoubtedly the TNF target cells. These findings confirm the synthesis of TNF alpha in advanced stage renal graft rejection.

Hepatocellular carcinoma in woodchuck were characterized for woodchuck hepatitis virus integration nea c-myc oncogene. In one tumor, viral integration resulted in overexpression of a c-myc viral cotranscript. In a second tumor, viral insertion, 600 bp upstream of c-myc exon 1, was associated with increased levels of normal c-myc mRNA. These results demonstrate that integration of woodchuck hepatitis virus near a proto-oncogene can contribute to the genesis of liver tumors. From a comparison of a single hepatitis B virus (HBV) integration site in a human hepatoma with the corresponding unoccupied site have shown HBV DNA insertion in a putative cellular exon. This exon presented striking similarity to the DNA-binding domain of the thyroid/steriod hormones receptors. The corresponding cDNA has been isolated (hap gene) as shown to encode the retinoic acid receptor. It is most probable that consequent to HBV insertion, hap gene became inappropriately expressed as an altered chimaeric gene retinoic acid receptor, thus contributing to the cell transformation. As for woodchuck these results strongly support the possibility that HBV, may play a direct role in liver carcinogenesis by insertional mutagenesis.

The Currarino triad consists of an anorectal malformation, a presacral tumor and a sacrum defect. A new case is reported in a female neonate. The diagnosis was suspected because of delayed emission of meconium associated with an occlusion syndrome. It was confirmed by bone imaging, ultrasonography and magnetic resonance imaging. A colostomy was performed on day 7 then closed on day 43 after several rectal dilation were carried out. A presacral lipoma was operated on at 10 months. The 56 cases reported in the literature are reviewed.

A thorough study of the genetic aspects of Klippel-Trenaunay syndrome revealed two further cases of K.T. in the family 2 of the 86 patients questioned. In addition, 7/4,000 first degree relatives had flat angiomas. The authors suggest that these individuals are in fact "mini-Klippels". "Formes frustes" of the syndrome can be explained by variable expression of the genetic defect. In all, 7/86 families were of particular genetic interest: - two families with two individuals suffering from KTS; - five families with several individuals with flat angiomas on one or more limbs. All these findings suggest multifactorial inheritance of the syndrome. It is not possible to calculate the precise probability of inheritance of the syndrome on the basis of our figures but we consider it to be of the order of 1 to 2%.

A new cell line derived from a thyroid anaplastic carcinoma, CAL 62, has been established in culture. This line is constituted by highly tumorigenic cells. Their epithelial phenotype is stable in culture. Immunochemical staining for human thyroglobulin is negative. Cytogenetic analysis showed a gain of chromosome 20, the translocation i (14q), and breakpoints of centrometric chromatine. These results are similar to those previously reported by other investigators. CAL 62 radiosensibility has been studied. The survival curve of the in vitro irradiated cells has been adjusted with a linear-quadratic model. This cell line is thus showed to be radioresistant. Cell line CAL 62 constitutes an appropriate model for in vitro studies of thyroid anaplastic carcinoma.

Two cases of acute megakaryoblastic leukemia in a 4 month-old and a 13 year-old girl are described. In the first case who presented with a large hepatomegaly and portal fibrosis, the diagnosis was made from the surface phenotyping of megakaryoblasts; a trisomy 13, 14 and 19 and an extra chromosome X were present in the bone marrow. An electron microscopy study of megakaryoblasts was necessary to identify the second case. Both children died shortly after treatment (cytosine-arabinoside at low dosage in the first case and polychemotherapy in the second). The 51 other cases reported in the literature are reviewed.

Through flow cytometry, we have analysed DNA content of cervical cells recovered by scrapping the uterine cervix in 1) 103 women without human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN), 2) 42 patients with HPV infection without CIN, and 45 patients with CIN. We have observed four different DNA patterns: 1) normal DNA pattern, 2) increased and heterogeneous DNA pattern (IH), 3) increased S G2 + M phases, and 4) DNA aneuploid pattern. Statistical calculation has emphasized the significant correlation linking flow cytometric DNA pattern with cytologic diagnosis. HPV infection without CIN was associated with IH DNA pattern and CIN with increased S G2 + M phases or DNA aneuploid pattern. These results point out the interest of flow cytometric analysis of DNA content in uterine cervix pathology and in more extend in infectious or preneoplastic pathology.

We have studied the configuration of genes encoding for the heavy and light chains in the tumoral cells of 6 patients affected by alpha heavy chain disease (alpha HCD). The results showed the presence of rearrangement of the alpha heavy chain as well as the kappa light chain genes whereas the lambda genes were in germinal configuration. Thus, these results suggest the presence of a monoclonal compound in the tumoral cells in the alpha HCD.

A variety of clinical, topographical, histological, epidemiological and geographical arguments attribute to the effects of solar radiation and to ultraviolet rays (UV) in particular, a decisive role in the processes of cutaneous carcinogenesis. This carcinogenicity is part of a series of chronic changes affecting the integument which constitute heliodermatitis or photosenescence. The effects of UV are cumulative. DNA is the main target of UV rays. Man possesses several DNA repair systems. The hereditary malfunction of part of these systems result in xeroderma pigmentosum, which constitutes a pathological model of photocarcinogenesis. Intrinsic skin ageing (non-photodependent) appears to promote this process of photocarcinogenicity by several mechanisms: summation of DNA changes, progressive deterioration of repair systems, dermal-epidermal atrophy, melanocytic changes, immuno-surveillance deficit.

Activity and phenotype of red blood cell esterase D were systematically determined in a population of 128 retinoblastoma patients from 99 families and compared to 158 controls, in order to detect a chromosome 13q14 deletion. Among these patients 12 were healthy carriers and 116 affected carriers of a mutant allele of the retinoblastoma susceptibility gene (110 retinoblastoma, 5 retinoma, 1 phtisis bulbi). 4 patients were found to have decreased ESD levels in connection with 13q14 deletion which was confirmed by chromosome analysis. The data presented here suggest that ESD quantification has a high specificity and sensitivity for the detection of homogenous chromosome 13 deletions in retinoblastoma patients.

In primary hyperparathyroidism, hypercalcaemia is due to inappropriate hypersecretion of parathormone (PTH). Yet, the intestinal or osseous origin of the excess in plasma calcium and the symptoms of the disease are largely conditioned by vitamin D reserve and metabolism. In cases with sufficient vitamin D reserve and normal metabolism, the primary disorder is hyperabsorption of calcium by the intestine, and there is a risk of renal stone formation. In patients with vitamin D deficiency, there is a significant increase of bone resorption accompanied by osteoarticular symptoms. In addition, other factors, as yet unidentified, seem to intervene in the reabsorption of calcium by the renal tubule, which commands the degree of hypercalcaemia. Hypersecretion of parathormone may be due either to a reduced sensitivity of parathyroid cells to calcium (as in adenomas) or to an increase of the PTH-secreting thyroid mass (as in hyperplasia and some adenomas).