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Biomedical subjects

A Donna

Publications and source records attributed to A Donna.

At least 19 recordsLinked to original sources
PubMed1997

Newly marketed tissue markers for malignant mesothelioma: immunoreactivity of rabbit AMAD-2 antiserum compared with monoclonal antibody HBME-1 and a review of the literature on so-called antimesothelioma antibodies.

A complementary DNA (cDNA) library was constructed from a human malignant mesothelioma (MM) cell line and a cDNA fragment encoding for a cytoplasmic mesothelial protein recognized by the polyclonal antibody AMAD-1 was then cloned and expressed in Escherichia coli. The purified recombinant protein was used to raise a novel antibody, named AMAD-2, in rabbits. This antibody reacted with normal mesothelium and most MM (15 of 17) on paraffin sections and featured a cytoplasmic labeling. Conversely, AMAD-2 immunostaining of normal and tumor tissues from body sites other than serosal membranes was limited with respect to the proportion of positive specimens and usually less conspicuous than in MM. AMAD-2 immunoreactivity was subsequently compared with staining for HBME-1, another newly marketed antimesothelial monoclonal antibody, concerning the ability to distinguish pleural MM from metastatic pleural tumors of epithelial type. A granular cytoplasmic immunoreactivity for AMAD-2 was present in 50% or more of tumor cells in all 84 MM, regardless of histological type, but also in 3 (7%) of 42 pleural metastases, albeit only focally. HBME-1 was shown in 63 of 66 epithelial MM and in the epithelial component of all 8 mixed MM, with a prevailingly membranous pattern, usually homogeneous and strong, whereas none of the 10 sarcomatous MM was positive. HBME-1 was also expressed in 6 (14%) of 42 pleural metastases in a cytoplasmic or membranous pattern. Compared with HBME-1, AMAD-2 showed a higher degree of specificity and sensitivity for MM. AMAD-2 still proved to be superior to HBME-1, also when sarcomatoid MM were excluded from the assessment. This finding supports the view that AMAD-2 is an antibody highly, although not entirely, specific for the mesothelial lineage, whereas HBME-1 is probably a cell marker more closely related to the epithelial differentiation of MM. Therefore, AMAD-2 is preferable as a positive tissue marker to be incorporated in the optimal immunohistochemical panel for the diagnosis of MM.

Antibodies, Monoclonal↗
PubMed1997

Malignant mesothelioma of the pleura. The reproducibility of the immunohistological diagnosis.

The reproducibility of the histopathological diagnosis of pleural malignant mesothelioma (MM), after supplementing routine H&E stain by immunohistochemistry (IH) in 77 cases of original diagnoses of MM, was assessed by examining interobserver variation between five pathologists. A battery of commercial antibodies (cytokeratins, vimentin, HMFG-2, anti Leu-M1 [CD15], BerEP4, B72.3 [TAG-72], carcinoembyonic antigen), considered to be useful in enhancing diagnostic accuracy, was used. The number of definitively classified tumors (accepted MM plus rejected MM) increased from 57 on H&E stain to 60 after IH, with 59 (76.6%) cases being accepted as true MM. Based on IH, the chance-adjusted interobserver agreement was poor (kappa w = 0.29) and lower than that observed on previous H&E alone. The intraobserver agreement for four of the five pathologists was rather good (kappa w = 0.54-0.56). The inter- and intraobserver concordance was higher in accepting than excluding the cases as MM. A larger number of cases were classified by all reviewers as mixed or sarcomatous variants after IH. In the interpretation of each immunostain, kappa values ranged from 0.19 for B72.3 to 0.62 for HMFG-2, which were respectively the least and the most consistently interpreted immunostains. The information additionally contributed by IH did not seem to change the pathologists' diagnoses very much in comparison with those made by routine H&E stain. Until highly specific and sensitive probes for the positive identification of MM become available, a careful scrutiny of routinely stained preparations still remains the most rewarding component of the diagnostic pathway.

Clinical Laboratory Techniques↗
PubMed1996

Pleural epidermoid carcinoma from displaced skin following extrapleural pneumothorax in a patient exposed to asbestos.

This report illustrates a rare case of primary epidermoid carcinoma of the pleura in a patient previously treated by artificial extrapleural pneumothorax for active tuberculosis. The patient had also been occupationally exposed to asbestos. Light microscopic examination showed two different lesions: laminar pleural fragments were covered by normal squamous epithelium that was similar in all respects to epidermis, whereas nodular fragments were composed of well-differentiated infiltrating carcinoma. These findings support the hypothesis that the carcinoma arose from normal epidermis seeded in the pleural cavity during multiple air refills to maintain the pneumothorax. A possible interaction between asbestos fibres and chronic inflammation might have potentiated tumour development.

Aged↗
PubMed1995

Malignant mesothelioma of the pleura: interobserver variability.

AIMS: To assess the consistency of histopathological diagnosis of pleural malignant mesothelioma by estimating interobserver agreement between five pathologists. METHODS: Eighty eight histological sets pertaining to original diagnoses of pleural malignant mesothelioma were reviewed separately by each pathologist. Diagnostic likelihood was graded as definite (A), probable (B), possible (C), improbable (D), and definitely not (E) malignant mesothelioma. The following indexes were estimated: observed proportion of agreement (Po), kappa statistics and proportion of agreement for "positive" (Ppos) and "negative" (Pneg) diagnoses. RESULTS: Sixty cases (68.2%) were rated by at least three reviewers as A or B and by none of the others as D or E. Five (5.7%) were rated by at least two reviewers as D or E and by none of the others as A or B. Nine (10.2%) showed a serious disagreement, rated A or B and D or E. Agreement for sets obtained at necropsy/surgery (median kappa w = 0.57) was similar to that for endoscopic material (median kappa w = 0.54). Agreement was poor on material obtained by needle biopsy (median kappa w = 0.21). The median value of Ppos varied between 0.94 (necropsy/surgery) and 0.67 (needle biopsy) and that of Pneg between 0.78 (necropsy/surgery) and 0.34 (unspecified biopsy). Interobserver agreement on histological typing was good overall (median kappa = 0.59). CONCLUSIONS: Of the original histological diagnoses, 70% were consistently reproduced through panel review. Most indexes of agreement between pathologists ranged from poor (needle biopsy) to moderate (necropsy/surgery). Agreement in confirming malignant mesothelioma was greater than that regarding exclusion of this diagnosis. Of the cases finally considered to have malignant mesothelioma, the reproducibility of histological typing was relatively satisfactory.

Aged↗
PubMed1992

Cytologic diagnosis of malignant mesothelioma in serous effusions using an antimesothelial-cell antibody.

Differentiating mesothelioma, reactive mesothelium, and adenocarcinoma in serous effusions is often difficult, despite the application of ancillary techniques in support of the traditional cytomorphologic criteria. A polyclonal antimesothelial-cell antibody recently developed by our group was evaluated as a histogenetic marker on a series of primary (n = 12) and metastatic (n = 12) malignant effusions. Immunostaining was performed on paraffin sections from cell blocks. All mesothelioma effusions stained positive for the antibody, whereas, in contrast, all metastatic carcinoma specimens failed to react. These results (100 percent specificity and 100% sensitivity for mesothelioma) provide a basis for a reliable use of the antibody in the cytologic examination of suspicious or malignant serous effusions.

Adenocarcinoma↗
PubMed1992

Quantitative analysis of nucleoli and nucleolar organizer regions in cultured primary human normal, reactive and malignant mesothelial cells.

The number and the size of silver-stained intranuclear granules, which correspond to the nucleolus and nucleolar organizer regions, have been determined by means of quantitative methods in cultured primary human mesothelial cells obtained from normal, reactive and malignant mesothelium. The mean values per nucleus of the number, the total area, the average area, and the relative area of the silver-stained granules and the mean nuclear area were determined for each of the three conditions. Normal, reactive and malignant mesothelial cells differed significantly in all the features. These findings at the optical level reflect the differing rate of the nucleolar biosynthetic activity related to the different biological properties of the three cell types, and the features can be useful morphometric descriptors in the diagnostic pathology of the mesothelium.

Ascitic Fluid↗
PubMed1992

Synovial sarcoma: a new approach to the histological classification and a comparison with malignant mesothelioma. Immunohistochemical study with anti-mesothelial cell serum.

Routine paraffin-embedded sections from synovial sarcomas in 70 patients were stained immunohistochemically with monoclonal anti-cytokeratin antibody and serum against mesothelial cells. Positive reactions occurred in the epithelioid cells of biphasic tumors only. On the ground of the reaction with anti-mesothelial serum a hypothetical scheme of cell differentiation in synovial sarcoma was set up.

Antibodies, Monoclonal↗
PubMed1992

Mitogenic effects of a mesothelial cell growth factor: evidence for a potential autocrine regulation of normal and malignant mesothelial cell proliferation.

We have investigated the growth-factor-like activity of a approximately 200-kDa, IP 8.3, cytoplasmic glycoprotein, the expression of which appears to be restricted to normal and malignant human mesothelium. This substance stimulated the growth of human mesothelioma cell cultures at greater rates than did foetal calf serum, but it failed to induce proliferation of lung carcinoma cell cultures. In addition, we have tried to trace the biosynthetic pathway of this mitogenic factor in normal human mesothelial cells by means of immuno-electron microscopy with a polyclonal antibody directed against this molecule. Positive immunogold labelling was found in the lumina of the cisternae of the endoplasmic reticulum, to a lesser extent on the outer surface of the plasma membrane, and also in structures corresponding to the coated pits. These ultrastructural findings are consistent with the hypothesis of the glycosylation of the newly synthesized protein in the endoplasmic reticulum and the subsequent uptake of the secreted molecule, which accumulates in the coated pits before internalization. The results suggest that this mitogenic glycoprotein could play a role in an autocrine growth control mechanism influencing mesothelial cell proliferation.

Coated Pits, Cell-Membrane↗
PubMed1991

A new insight into the histogenesis of 'mesodermomas'--malignant mesotheliomas.

A myogenic phenotype was induced in cultures of human mesothelial cells treated for 72 h with atrazine, a triazine derivative. Immunoreactivity for both myosin and myoglobin was detected in a large number of these cells, irrespective of their polygonal or spindle morphology, whereas no expression of desmin was observed. These findings support the embryological identity of mesothelium and mesoderm, the former being, in the post-embryonic stage, potentially capable of differentiation along the same lineages which the latter normally displays during embryogenesis. In the light of this concept it can be assumed that primary malignancies arising from the mesothelium have the competence to express the pluripotent nature of embryonic mesoderm, and hence the term mesodermoma is appropriate for this group of tumours, including mesotheliomas in a classical sense. A postulated mechanism for the phenotypic change of mesothelial cells is also outlined, involving atrazine conversion to 5-aza-chloro-cytidine, a probable DNA hypomethylating and gene activating agent, like its analogue 5-azacytidine.

Atrazine↗
PubMed1991

A one-year carcinogenicity study with 2,6-dichlorobenzonitrile (Dichlobenil) in male Swiss mice: preliminary note.

2,6-Dichlorobenzonitrile (Dichlobenil) is the active principle of a commercial herbicide that was previously shown to be carcinogenic for animals. Dichlobenil was administered to male Swiss albino mice in order to assess the possible oncogenic properties of the active principle alone. The substance at 2 ppm concentration was injected (0.0005 mg/injection) either by subcutaneous or intraperitoneal route to 2 randomized groups of 30 animals each every third day for 13 times. Dichlobenil induced a significant increase of malignant tumors (lymphoma, mesothelioma, hepatocellular carcinoma, and pulmonary alveologenic carcinoma) with respect to the controls (p less than 0.01 in both treated groups). As for tumor histotypes, only lymphoma incidence was significantly increased in the intraperitoneally treated animals (p less than 0.05). Dichlobenil can be suspected of being a possible carcinogen in Swiss mice but the mechanism of its action is not precisely known.

Animals↗
PubMed1990

A morphometrically-based classification rule for the diagnosis of primary mesothelial lesions.

A computer-aided morphometrical study was performed on histological specimens of reactive hyperplastic (n = 10) and malignant (n = 17) mesothelium. For each cell, seven nuclear features were measured and 13 parameters computed. Using stepwise variable selection, discriminant analysis chose the nuclear contour index, the standard deviation of the nuclear area, and the mean of the nuclear perimeter as discriminating features between hyperplastic and malignant mesothelium. The coefficients of these variables were included in a discriminant function which gave perfect discrimination between the two groups of lesions. When the function was assessed on a test set of hyperplastic (n = 10) and malignant (n = 17) mesothelial lesions treated as 'unknown', complete separation between these two diagnostic categories was achieved. This classification rule may help to increase the level of confidence with which a histological diagnosis of mesothelioma can be established.

Cell Nucleus↗
PubMed1989

Verification of the histologic diagnosis of malignant mesothelioma in relation to the binding of an antimesothelial cell antibody.

The diagnostic value of a recently developed polyclonal antibody to mesothelial cells has been tested by means of an immunoperoxidase technique to differentiate mesothelioma from lung carcinoma. All 16 unequivocal mesotheliomas reacted with the antibody, whereas none of the 31 lung carcinomas did, thus confirming the high specificity and the high sensitivity of the antibody. Furthermore, 20 cases of serous membranes tumor, in which major diagnostic disagreement was present when reviewed by the members of the Commission of the European Communities Mesothelioma Panel, were examined. Sixteen of the 20 cases were immunoreactive to the antimesothelial cell antibody, thus establishing their mesothelial origin. Given conventionally fixed and processed tissues, it appears that this antibody may be used as an appropriate diagnostic adjunct to increase the accuracy of the diagnosis of mesothelioma.

Antibodies, Neoplasm↗
PubMed1989

Mesotheliomas of the tunica vaginalis testis and hernial sacs.

Three histologically and immunohistochemically well-documented cases of mesothelioma of the tunica vaginalis testis and hernial sac are presented. Analysis and follow-up data on our three patients and a review of 30 previously reported cases have revealed a varied and often unpredictable clinical course. A classification into high- and lowgrade malignant tumours is suggested, based on clinical and pathological findings.

Aged↗
PubMed1989

Putative mesothelial cell growth-promoting activity of a cytoplasmic protein expressed by the mesothelial cell. A preliminary report.

Mesothelioma cells produce a cytoplasmic protein unique to primary tumours of the mesothelium which induces the in vitro proliferation of human mesothelial cells in a dose-dependent fashion. When a polyclonal antibody to this protein was added to cultures of human mesothelioma cells, inhibition of their growth occurred. These results provide evidence for a growth-factor-like role of this mesothelial protein that may act through an autocrine mechanism.

Cell Division↗
PubMed1989

Triazine herbicides and ovarian epithelial neoplasms.

The possible role of a class of herbicides, triazines, in ovarian carcinogenesis has been evaluated in a population-based case-referent study. The trade names reported by the study subjects, and the type of cultivation in which they worked, were used for the assessment of exposure. Women previously exposed to triazines showed a significant relative risk of 2.7 for ovarian neoplasms. Although none of the doses could be quantified for the study subjects, two risk trends in favor of the plausibility of the association were found: the first by duration and the second by probability of exposure. The population representativity of the study and the comparability of information between the cases and referents suggest the lack of any major bias in the results. Triazine-related risk remained consistent when the analysis was restricted to farmers and when the exposure to other herbicides and to other types of cultivation were considered. Unexposed farmers had the same risk as unexposed nonfarmers.

Adult↗
PubMed1988

Adenomatoid tumour of the uterus.

Two adenomatoid tumours of the uterus were examined immunohistochemically using antibodies to keratin, Factor VIII related antigen, EMA, CEA and a specific protein isolated from mesothelioma cells. The tumour cells gave positive staining for keratin and for the specific mesothelial marker. The results strongly support a mesothelial origin for adenomatoid tumours and this panel of antibodies may be used to solve diagnostic problems.

Adult↗