European recommendations and quality assurance for cytogenomic analysis of haematological neoplasms.

Cytogenomic investigations of haematological neoplasms, including chromosome banding analysis, fluorescence in situ hybridisation (FISH) and microarray analyses have become increasingly important in the clinical management of patients with haematological neoplasms. The widespread implementation of these techniques in genetic diagnostics has highlighted the need for guidance on the essential criteria to follow when providing cytogenomic testing, regardless of choice of methodology. These recommendations provide an updated, practical and easily available document that will assist laboratories in the choice of testing and methodology enabling them to operate within acceptable standards and maintain a quality service.

Sporadic fundic gland polyps: an immunohistochemical study of their antigenic profile.

Fundic Gland Polyps (FGPs) are small sessile (2-5 mm), usually multiple polyps arising in the gastric, acid-secreting mucosa of disputed histogenesis. They have been described in a sporadic form, prevalently in middle aged females, or associated with familial adenomatosis coli-Gardner's syndrome. We performed an immunohistochemical study on 24 sporadic FGPs, using monoclonal antibodies (MAbs) against differentiation markers, class II MHC antigens (HLA-DR), oncofetal and proliferation antigens, aimed to characterize the antigenic profile of the polyps. A preliminary cytogenetic study on five polyps was also done, using an in situ culture method after collagenase treatment. Cytokeratins 8-18 (CAM 5.2 MAb) and 20 (IT-Ks 20.8 MAb), Epithelial Membrane Antigen (EMA) and Chromogranin A were normally expressed by FGPs. FGPs did not express HLA II DR. FGPs did not react with an anti-CEA MAb (F6), but they were frequently positive (22/24, 91.6%) with B72.3 MAb (reacting with the cancer-associated mucin epitope sialyl-Tn). The PC10 MAb (against PCNA or cyclin) showed enhanced expression in the deep glandular-cystic compartment of FGPs; the PCNA index of FGPs was significantly higher than in normal fundic mucosa. The cytogenetic study on the 5 cases analysed, revealed a normal karyotype. We have demonstrated that FGPs express in the paranuclear zone the sialyl-Tn epitope, a side-chain sugar normally masqued in adult gastric mucins, thus revealing an alteration in mucin synthesis; FGPs' higher proliferation index as compared with normal fundic mucosa supports the hypothesis of their hyperproliferative nature.

Genetic diagnosis by chorionic villus sampling before 8 gestational weeks: efficiency, reliability, and risks on 317 completed pregnancies.

Transabdominal chorionic villus sampling (TA-CVS) was attempted in 328 high-risk pregnancies at 6-7 weeks of gestation. Sampling was feasible in 97.7 per cent of cases; chorionic tissue specimens of more than 10 mg were obtained in 94.4 per cent of cases at the first needle insertion and in 100 per cent after a second attempt. Fetal karyotyping succeeded in 99.4 per cent of cases, while no diagnostic failures were reported in enzymatic and DNA analyses. Fetal loss rate in the first 4 weeks after CVS was significantly higher than in the later CVS series (7.2 vs. 2.5 per cent), but 50 per cent of losses were observed within 2 weeks in cases of inviable aneuploidies. A high incidence of severe limb abnormalities (1.6 per cent) was detected in pregnancies intended to continue, confirming the aetiological role of early CVS. Unclear visualization of the placental limits and poor control of the needle path are thought to be the main reasons for the vascular disruption of the chorionic plate, and thereby hypoxic embryo tissue damage. A better selection of cases, together with high-resolution vaginal ultrasound visualization, and analytical techniques requiring a minimal amount of tissue should avoid any teratogenic effect of early CVS.

First-trimester prenatal diagnosis of Roberts syndrome.

We present a case of prenatal detection of premature centromere separation on chorionic villi sampled at 8 weeks' gestation from a woman at risk of recurrence of Roberts syndrome. The same cytogenetic characteristic was confirmed on amniocytes at 14 weeks when ultrasound examination showed morphological anomalies of the fetus. To our knowledge, this is the first report of early prenatal diagnosis of Roberts syndrome.

Multiple clonal chromosome abnormalities in Peyronie's disease.

Numerical and structural chromosome aberrations were found in cell plaque metaphases from 9 of 14 patients with Peyronie's disease. In two cases there was evidence of clonal evolution for some of the chromosomal aberrations observed. The Y chromosome was the most frequently involved in numerical changes. Four of 9 cases with abnormal karyotype showed more than one abnormal, cytogenetically unrelated clone. Our findings suggest the possibility of a multiclonal origin for this benign tumor, and confirm the presence of chromosome instability in this cell growth disorder.

Trisomic 22 placenta in a case of severe intrauterine growth retardation.

We describe a case in which a trisomic 22 placenta could be the cause of severe growth retardation in a chromosomally normal female fetus. At amniocentesis a mosaic 46,XX/47,XX, +22 was observed in amniotic fluid specimens sampled on two different occasions, while fetal blood from a diagnostic cordocentesis revealed a normal chromosome constitution. Postnatal studies showed the consistent presence of trisomic 22 cells in the placenta, while only normal metaphases were found in amnion, blood, and fibroblast cultures.