Multiparametric study (SAMBA 200) of estrogen receptor immunocytochemical assay in 400 human breast carcinomas: analysis of estrogen receptor distribution heterogeneity in tissues and correlations with dextran coated charcoal assays and morphological data.

Estrogen receptor (ER) immunocytochemical assay (ER-ICA) was assessed in 400 human breast carcinomas. In all cases, patient's age, tumor size, histological type and Scarff-Bloom-Richardson grade, and presence or absence of axillary lymph node metastases and of vessel invasion in tumor borders were recorded. In 310 cases estrogen and progesterone receptors were concomitantly evaluated (dextran coated charcoal method). In 60 of these cases the ER immunoenzymatic assay (ER-IEA) was also assessed. Monoclonal H222sp gamma and peroxidase antiperoxidase procedures (Abbott kit) were applied in frozen sections, tumor imprints, and fine-needle aspirates. A computerized system of image analysis referred to as SAMBA (TITN), permitted a multiparametric quantitative analysis of ER-positive surfaces. With this system, in each tumor, the cellularity, percentage of ER surface versus the total cell surface and versus the epithelial (keratin-positive) surface, integrated optical density, mean optical density, index of the concentration of labeled objects, and integrated optical density histograms, were obtained and correlated to histological and biochemical data. It was shown that (a) ER antigenic sites were heterogeneously distributed in ER-positive tumors, with a specific nuclear localization in epithelial cells; (b) SAMBA 200 multiparametric analysis of the ER sites distribution in tissue was appropriate, accurate, reproducible, and therefore more reliable than the semiquantitative analysis; (c) standardization and complete automation of this method of immunoprecipitates evaluation on tissue section permits daily and routine analysis of a large number of preparations; (d) there was a correlation between ER binding sites evaluation (dextran coated charcoal) and ER antigenic sites immunodetection (ER-ICA and ER-IEA); (e) there was a correlation between the SAMBA evaluation of ER-ICA and other histological prognostic factors such as small tumor size, low Scarff-Bloom-Richardson grade; (f) the preliminary SAMBA analysis of ER-ICA in tissue sections, imprints, and fine needle aspirates suggest that fine needle aspirates may not reflect accurately the tumor cell heterogeneity.

Correlation between polysialic-neural cell adhesion molecule levels in CSF and medulloblastoma outcomes.

PURPOSE: To quantify CSF levels of polysialic-neural cell adhesion molecule (PSA-NCAM) in patients with medulloblastoma (MB) metastasis, to assess the correlation with other diagnostic techniques (imaging and cytology) and clinical features, and to determine whether it is a suitable marker to monitor response to treatment and subsequent follow-up data. PATIENTS AND METHODS: PSA-NCAM levels were measured using a double-site enzyme-linked immunoadsorbant assay (ELISA) in 145 samples from 14 controls and 29 patients with MB. Clinical status of patients, imaging, and cytologic data were available at the time of each lumbar puncture. Medians and ranges for the 131 pooled PSA-NCAM concentrations were calculated for the MB versus the control groups, and for MB patients for normal versus abnormal groups at cytology or imaging, and for four clinical subgroups, respectively. For patients with MB, three PSA-NCAM measurements that corresponded to punctures performed during three time periods following surgery were selected. The kappa measure of agreement was calculated between normal and abnormal groups at cytology or imaging, and between groups of patients in remission and refractory, respectively. For the same phases, sensitivity and specificity of PSA-NCAM and cytology tests and their 95% confidence intervals (95% CIs) were computed. RESULTS: PSA-NCAM was never detected in control CSF. PSA-NCAM concentration medians were higher in CSF with metastatic cells or that corresponded to abnormal imaging than in the corresponding normal groups (P < .05). The PSA-NCAM concentration median was significantly higher (P < .05) in CSF from patients refractory to treatment or who relapsed than from patients in remission. Agreements between PSA-NCAM and clinical status and between PSA-NCAM and cytology were excellent during and after treatment. The sensitivity of PSA-NCAM test was always better than that of cytology, whereas its specificity was lower for phases that corresponded to more than 1 month following surgery. However, specificity was 100% for patients refractory to treatment or with relapse. CONCLUSION: PSA-NCAM measurement appears to be a new biologic marker of possible use in the management of patients with MB.

Peripheral neuropathy induced by amiodarone chlorhydrate. A clinicopathological study.

Four cases of amiodarone neuropathy are reported. Patients presented a sensorimotor neuropathy with distal predominance. Improvement occurred after drug discontinuation. Nerve conduction velocities were significantly decreased. Other secondary effects of amiodarone were noted in two cases. In one case serum levels of amiodarone and N-monodesethylamiodarone were evaluated during and after treatment. Pathological study of nerve with morphometric evaluation was performed. Axonal degeneration changes were predominant in 3 cases. Aspects of segmental demyelination and remyelination were noted in one case and related to secondary demyelination. Numerous lysosomal inclusions were present in Schwann cells, fibroblasts, capillary endothelial and perithelial cells and in perineural cells. Similar inclusions have been observed in other drug-induced lipidosis. The factors responsible for this neuropathy are unknown. In one case, amiodarone-induced hepatic failure might explain the persisting high serum levels of the drug.

Correlation between cytogenetic and histopathological findings in 75 human meningiomas.

The correlations between cytogenetic and histopathological findings were analyzed in 75 human meningiomas. The tumors were classified according to increasing degrees of anaplasia into three grades: Grade I, benign; Grade II, atypical; Grade III, anaplastic. In 45 tumors of Grade I (benign), we more often observed a normal karyotype or monosomy 22. In 23 tumors of Grade II (atypical), we observed karyotypes with structural and/or numerical abnormalities with the presence of telomeric associations in 8 of them. These last tumors were fibroblastic. In seven Grade III tumors (anaplastic), we also observed complex abnormalities, and in one case, we observed telomeric associations. Our observations show that complex chromosome abnormalities and telomeric associations are observed in tumors that histologically display a certain degree of anaplasia. It is possible that the result of histopathological and cytogenetic correlations might represent a prognostic factor in meningiomas.

[Tomaculous neuropathy. A histopathological study and electroclinical correlates in 10 cases]. / Neuropathie tomaculaire. Etude histopathologique et corrélations électrocliniques dans 10 cas.

Among 980 sural nerve biopsies, the nerves of 10 patients showed a great number of focal sausage-shaped thickenings of the myelin sheaths and were investigated by light and electron microscopy, teasing and quantitative studies. Single teased nerve fibres revealed myelin thickening in more than 25 p. 100 of internodes. This condition defined the tomaculous neuropathy and differed from other degenerative or toxic neuropathies which displayed a small number of internodes with myelin thickenings, in less than 5 p. 100. Segmental demyelination and remyelination were found in 12 p. 100 to 65 p. 100 of myelinated fibres. Tomaculous swellings were observed in the internodes of these fibres. Except axonal constriction within the sausage-shaped thickenings, no fibers with axonal degeneration was observed. The density of myelinated and unmyelinated fibres was normal. The loss of large myelinated fibres was interpreted as resulting from the myelinic changes. Clinical and electrophysiological data were similar in the ten cases of tomaculous neuropathies and in hereditary neuropathy with liability to pressure palsies, i.e.: autosomal dominant inheritance, higher incidence in males, recurrent nerve trunck and/or brachial plexus involvement related to compression, slowing of nerve conduction velocities in clinically affected and unaffected nerves more pronounced in anatomical narrow sites and increased F wave latencies. One patient (case 10) showed a mixed sensory motor progressive neuropathy but signs of widespread neuropathy were noted in more advanced cases. A great number of tomaculous swellings of myelin sheaths is considered as a specific but non constant change of hereditary neuropathy with liability to pressure palsies.

[Incidence of the morphological aspect on the rate of implantation of embryos obtained by fertilization in vitro]. / Incidence de l'aspect morphologique sur le taux d'implantation des embryons obtenus par fécondation in vitro.

1350 embryos obtained by In Vitro Fertilization (IVF) have been examined with the reverse microscope before their transfer in utero. Some embryos are "morphologically normal" (34.7%); some others are atypical. It is difficult to determinate the implantation rate by embryo according to morphological aspect because, most of the time we transfer several embryos to only one patient and we do not know, in case of pregnancy, which one or which ones have developed. Nevertheless, we have tried to appreciate, for 500 embryos transfers after IVF, the incidence of morphological aspect according to the presence or absence of "morphologically normal" embryos. The implantation rate is significantly higher in the groups in which you find "morphological normal" embryos than in the group where they are missing. (19.7% and 19.2% vs 10.2%). It seems that the aspect of the embryo when it is transferred, has an incidence on its future development.