Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions.

Carcinoembryonic antigen (CEA), carbohydrate antigens 15-3, 19-9 and 72-4 (CA 15-3, CA 19-9 and CA 72-4), cytokeratin 19 fragments (CYFRA 21-1), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) were evaluated in pleural fluid for the diagnosis of malignant effusions. With a specificity of 99%, determined in a series of 121 benign effusions, the best individual diagnostic sensitivities in the whole series of 215 malignant effusions or in the subgroup of adenocarcinomas were observed with CEA, CA 15-3 and CA 72-4. As expected, a high sensitivity was obtained with SCC in squamous cell carcinomas and with NSE in small-cell lung carcinomas. CYFRA and/or CA 15-3 were frequently increased in mesotheliomas. Discriminant analysis showed that the optimal combination for diagnosis of non-lymphomatous malignant effusions was CEA + CA 15-3 + CYFRA + NSE: sensitivity of 94.4% with an overall specificity of 95%. In malignant effusions with a negative cytology, 83.9% were diagnosed using this association. The association CYFRA + NSE + SCC was able to discriminate adenocarcinomas from small-cell lung cancers. Regarding their sensitivity and their complementarity, CEA, CA 15-3, CYFRA 21-1, NSE and SCC appear to be very useful to improve the diagnosis of malignant pleural effusions.

Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions.

CYFRA 21-1 assay, measuring cytokeratin 19 fragments, was compared with carcinoembryonic antigen (CEA) assay, as an addition to cytological analysis for the diagnosis of malignant effusions. Both markers were determined with commercial enzyme immunoassays in pleural fluid from 196 patients. Cytological analysis and/or pleural biopsy confirmed the malignant origin of the effusion in 99 patients (76 carcinomas, nine pleural mesotheliomas and 14 non-epithelial malignancies). Effusions were confirmed as benign in 97 patients (33 cardiac failures, 39 infectious diseases--including 12 tuberculosis-- and 25 miscellaneous effusions). Both markers were significantly higher in malignant than in benign effusions. All the patients with non-epithelial malignancies presented CYFRA and CEA values lower than the 95% diagnostic specificity thresholds (100 and 6 ng ml(-1) respectively). The diagnostic sensitivity in the group of carcinomas and mesotheliomas was similar for CYFRA (58.8%) and CEA (64.7%). However, CEA had a significantly higher sensitivity in carcinomas (72.4% vs 55.3%), while CYFRA had a clearly higher sensitivity in mesotheliomas (89.9% vs 0%). Interestingly, 12 out of the 16 malignant effusions with a negative cytology were CEA and/or CYFRA positive. Regarding their high diagnostic sensitivity and their complementarity, CEA and CYFRA appear to be very useful for the diagnosis of malignant pleural effusions when cytology is negative.

[Comparative study of the expression of CEA and a myelomonocytic antigen (CD15) in serous effusions using two monoclonal antibodies NEO 723 and Leu M1]. / Etude Comparative de l'expression de l'ACE et d'un antigène myélomonocytaire (CD15) dans les épanchements des séreuses à l'aide de deux anticorps monoclonaux NEO 723 et Leu M1.

A comparative study of the reactivity of two monoclonal antibodies (MAb), NEO 723 (anti-CEA) and Leu M1 (CD15) was performed by immunocytochemistry on sixty five reactive effusions and sixty two neoplastic effusions, fifty eight due to metastases from carcinomas, two due to disseminations of sarcoma and two due to malignant mesotheliomas. The study of the expected reactivity of NEO 723 and the cross-reactivity of Leu M1 on exfoliated neoplastic cells in effusion fluids showed that the sensitivity of NEO 723 was superior to that of Leu M1 for the detection of carcinomatous metastases, as 78% reacted with NEO 723 versus 38% with Leu M1. Among the positive cases, the mean number of reactive cells was twice as high with NEO 723, while only three of the carcinomas no expressing CEA reacted with Leu M1. The study of the reactivity of benign and malignant mesothelial cells with these two antibodies also confirmed the absence of labelling of these cells. Thus, despite a good specificity for carcinoma, the combination of these two antibodies provides only a minor gain in diagnostic sensitivity (+5%) compared with the use of an anti-CEA antibody alone and a loss of sensitivity (-5%) compared with the combination of an anti-CEA and an anti-EMA antibodies. These results appear to justify the suppression of Leu M1 from the first panel of antibodies screening for carcinomatous cells in favour of a combination of anti-CEA and an anti-EMA antibodies. However, Leu M1 may be useful as a second-line test in order to define the primary tumour responsible for the effusion.

Immunophenotyping of mesothelial cells and carcinoma cells with monoclonal antibodies to cytokeratins, vimentin, CEA and EMA improves the cytodiagnosis of serous effusions.

This paper presents an immunocytochemical study performed on cytocentrifuged deposits from 109 peritoneal and pleural effusions including 20 transudates, 43 malignant metastatic effusions and 46 effusions containing atypical cells, unidentifiable as reactive mesothelial or malignant epithelial cells on the classical morphological criteria. A panel of four monoclonal antibodies (MAb) was used, including KL1 directed to cytokeratins (KER), V9 to vimentin (VIM), NEO 723 to carcinoembryonic antigen (CEA) and E29 to epithelial membrane antigen (EMA). In most transudates the reactive mesothelial cells coexpressed VIM and KER with a ring-like pattern for the latter proteins. In contrast, they were unreactive to anti-CEA and weakly and inconsistently reactive to anti-EMA. In malignant effusions, most carcinoma cells coexpressed EMA, CEA and KER with a predominant diffuse cytoplasmic pattern for the latter. Only a few malignant epithelial cells from five metastatic adenocarcinomas weakly expressed VIM. When used on the 46 effusions with unidentifiable cells, the panel of MAb allowed reactive mesothelial cells and malignant epithelial cells to be distinguished from each other in 39 of 46 cases (85%).

[Virus diseases and cancer of the vulva]. / Viroses et cancers de la vulve.

The study of cancers of the vulva, first of all, attempts to classify precancerous lesions of the external genital apparatus. The proceedings of the ISSVD were carried out here in 1975. Clinical, epidemiological and viral arguments of HPV and HSV have been considered in order to demonstrate their responsibility in neoplasms of the vulva. However, HPV seems the main cocarcinogen. Cancers of the vulva appear, therefore, as a true sexually transmitted disease and the authors emphasize a simultaneous monitoring of the cervix and the male genital apparatus.

Morphologic, quantitative and cytoenzymologic studies of synoviocytic and monocytic cells in synovial fluid.

The findings are presented of a morphologic, quantitative, cytochemical and cytoenzymologic study of the mononucleated nonlymphoid cells in knee synovial fluids from osteoarthritis and various inflammatory diseases. The morphologic criteria allowed the identification of subtypes, including phagocytic subtypes, among synoviocytic and monocytic cells in the fluids. The quantitative study showed an important afflux of monocytes and a hyperexfoliation of synoviocytes in the inflammatory diseases. In fluids with intermediate cellularity, the ratio of monocytes to synoviocytes allowed the differential cytodiagnosis between osteoarthrosis and arthritis. All monocytic subtypes, especially the phagocytic one, were highly significantly increased in the inflammatory diseases. A lower increase was shown by the synoviocytic subtypes, except the phagocytic one, which was not changed. Giant multinucleated synoviocytes were found in every type of disease and thus do not constitute a cytodiagnostic marker. Alcian blue staining without hyaluronidase treatment showed hyaluronate in only a small percentage of the synoviocytes. Cytoenzymologic study showed that synoviocytes and monocytes were positive for all tested hydrolases (beta glucuronidase, acid phosphatase and alpha naphthyl acetate esterase), with the reactivities always higher in the synoviocytes. The synoviocytes were always negative with peroxidase, so this reaction, although it marks only a minority of the monocytic population, can be used as an extra cytologic criterion for the discrimination of mononucleated cells in synovial fluid. There was no significant quantitative difference at the cellular level between osteoarthrosis and arthritides in the reaction to these four enzymes. The lysosomal enzymatic activity in both monocytic and synoviocytic cells confirmed their heterophagic properties. However, synoviocytic heterophagy seems to be a physiologic process, either little or not affected by inflammatory events. On the other hand, monocytic heterophagy and then the macrophagic transformation of monocytes appears to be a major aspect of intrasynovial inflammatory reactions. The question remains as to why, if a large majority of exfoliated synoviocytes comes from type A synovial-lining cells and if they belong to mononuclear phagocytic system, do they so weakly, or not at all, participate as phagocytes in the inflammatory reaction.

[Non-lymphoid mononucleated cells in the synovial fluid in arthrosis and various inflammatory arthropathies. Morphologic, quantitative and cytoenzymologic study]. / Les cellules mononucléées non lymphoïdes du liquide synovial dans l'arthrose et diverses arthropathies inflammatoires. Etude morphologique, quantitative et cyto-enzymologique.

This paper describes a morphologic, quantitative, cytochemical study of mononuclear non lymphoid cells in knee synovial fluid in osteoarthritis and various arthritides. Morphologic criteria allow to identify among these cells various synoviocytic and monocytic subtypes with in both types, phagocytic subtypes. Quantitative study shows in arthritides an important afflux of monocytes and a hyperexfoliation of synoviocytes. In fluids with intermediate cellularity, Monocytes/Synoviocytes ratio allows the differential cytodiagnosis between osteoarthrosis and arthritis. All monocytic subtypes and especially the phagocytic one are highly significantly increased in arthritides. Synoviocytic subtypes show a lower increase, except the phagocytic one, which is not changed. Giant multinuclear synoviocytes are found in every type of disease and cannot constitute a cytodiagnosis marker. Alcian Blue and hyaluronidase treatment show hyaluronate in a few percentage of Synoviocytes. Cytoenzymologic study shows that synoviocytes and monocytes are positive in all tested hydrolases: beta Glucuronidase, Acid Phosphatase, alpha Naphthyl Acetate Esterase, these activities being always higher in synoviocytes. With peroxidase, synoviocytes are always negative, so this reaction although it marks only a minority of monocytic population can be used as an extra cytologic criterion for discrimination of mononuclear cells in synovial fluid. In these four enzymes there is no significant quantitative difference at cellular level between osteoarthrosis and arthritides. Lysosomal enzymatic activity in both monocytic and synoviocytic cells confirms their heterophagic properties. However synoviocytic heterophagy seems to be a physiological process not or few affected by inflammatory events. On the opposite, monocytic heterophagy and then macrophagic transformation of monocytes appears as a major aspect of intrasynovial inflammatory reaction. If a large majority of exfoliated synoviocytes comes from A type synovial lining cells and if they belong to Mononuclear Phagocyte System, why do they so weakly, or not, participate as phagocytes to inflammatory reaction.

[Effects of small doses of ionizing radiation on embryonic development of the mouse]. / Effets de faibles doses de rayonnement ionisant sur le développement embryonnaire chez la souris.

Mice with vaginal plugs were irradiated, seven hours after mating, i.e near fecundation, by 5, 10 and 25 rads of gamma rays from a 60Co source. Females were sacrificed on the 18th day of gestation. The total number of implantations was unchanged after exposure to 5 and 10 rads but the frequency of resorptions was increased for all doses. No abnormalities were observed in testicles, kidneys and skeleton.