Biomedical subjects

M Papotti

Publications and source records attributed to M Papotti.

At least 127 records · Page 7Linked to original sources

PubMed1992

Detection of cytomegalovirus by in situ hybridization using a digoxigenin-tailed oligonucleotide.

A non-isotopic in situ hybridization procedure was used to detect cytomegalovirus (CMV) sequences within routinely fixed tissue. A digoxigenin-tailed oligonucleotide was hybridized to sections of specimens obtained at autopsy from 2 patients with CMV infection. Hybrids were revealed by an alkaline phosphatase-conjugated anti-digoxigenin antibody. Serial sections were also assayed for the presence of CMV by in situ hybridization with a biotin-labelled cDNA probe and by immunohistochemistry and routinely stained for morphological evaluation. Results show that the two in situ hybridization procedures are equally sensitive but superior to the immunohistochemical detection of the viral antigen. Most cells positive for CMV DNA had the cytopathological features characteristic of CMV infection. A minor population of infected cells lacking morphological changes was also found. We recommend the routine application of the oligonucleotide-based assay because it is specific, easy and less expensive than other similar procedures.

Alkaline Phosphatase↗

PubMed1992

Abnormal p53 expression in lung neuroendocrine tumors. Diagnostic and prognostic implications.

The diagnostic and prognostic implications of p53 immunostaining have been investigated in 59 pulmonary neuroendocrine tumors, including typical carcinoids (n = 15), so-called "atypical carcinoids" (n = 22), and small cell lung carcinomas (SCLCs; n = 22). Immunocytochemistry was performed on formalin-fixed, paraffin-embedded samples using the monoclonal antibody PAb1801, which has been shown to be suitable for staining fixed and embedded tissue sections. p53 immunoreactivity was restricted to atypical carcinoids (45% of the cases being immunoreactive) and to SCLCs (which were positively stained in 59% of the cases), whereas it was consistently lacking in typical carcinoid tumors. When the group of the so-called "atypical carcinoids" was further reclassified, p53 immunostaining was strictly confined to those cases belonging to the histologically more aggressive subsets (well differentiated neuroendocrine carcinoma subsets II and III). Within the same tumor type, however, p53 immunoreactivity did not correlate with the clinical outcome of the disease and was not predictive of the length of survival. The data indicate that abnormal p53 expression (which is strictly dependent on structural abnormalities of the p53 gene) is detectable in the majority of neuroendocrine carcinomas of the lung and might represent a useful adjunct in the differential diagnosis of pulmonary neuroendocrine neoplasms, particularly in routinely fixed and embedded small bronchoscopic biopsies.

Antibodies, Monoclonal↗

PubMed1991

Gastric carcinoids and their precursor lesions. A histologic and immunohistochemical study of 23 cases.

A histologic and immunohistochemical study was carried out in 23 unselected nonantral gastric carcinoids and their precursor lesions classified according to Solcia et al. None of the patients showed Zollinger-Ellison syndrome. Two variants of carcinoids showing distinctive pathologic and pathogenetic characteristics were identified on the basis of presence or absence of associated chronic atrophic gastritis type A (A-CAG). Chronic atrophic gastritis type A was found in 19 cases showing either single or multiple neoplasms, tumor extension limited to the mucosa or submucosa, consistent endocrine cell precursor changes in extratumoral mucosa, and consistent hypergastrinemia and/or G cell hyperplasia. Associated precursor lesions were only hyperplastic in all but two cases with single carcinoids whereas they were also dysplastic in all but one case with multiple carcinoids. The four tumors arising in nonatrophic mucosa were all single, more aggressive, and not associated with extratumoral endocrine cell proliferations or with signs of gastrin hypersecretion. Tumor cells were diffusely immunoreactive for chromogranin A and synaptophysin but usually negative for chromogranin B or HISL-19. Scattered serotonin cells were found in ten carcinoids. They were more frequent in infiltrating than in intramucosal tumors as were the less represented pancreatic polypeptide cells whereas the reverse was found for alpha-subunit-containing cells. These results are of relevance for tumor pathogenesis and may provide the rationale for a less aggressive therapeutic approach in the patients.

Adolescent↗

PubMed1991

Expression of the gastrin-releasing peptide gene in carcinomas of the breast.

Expression of gastrin-releasing peptide (GRP), the mammalian homologue of the amphibian bombesin, has been investigated at gene and protein level in a series of 28 primary breast carcinomas, in 6 mammary cancer cell lines and in one transplantable rat mammary carcinoma. Moderate to strong expression of GRP mRNA was detected in 5 breast carcinomas by Northern blot analysis with a pre-pro-GRP probe; 4 other cases were weakly reactive. Two of these cases also gave a specific immunocytochemical reaction for GRP, controlled with absorption experiments. Correlation with NE differentiation [as shown by chromogranins (Cg) and/or NSE and/or Grimelius positivity] was low, since only one case of breast carcinoma co-expressed GRP and Cg mRNAs. Breast cancer cell lines and a rat carcinoma gave negative results. GRP production in breast cancer did not appear to bear prognostic implications, but longer follow-up periods are needed to confirm these data. As shown in small-cell lung cancer, GRP might be involved in autocrine growth control mechanisms of a group of breast carcinomas.

Animals↗

PubMed1990

Cytologic features of poorly differentiated 'insular' carcinoma of the thyroid, as revealed by fine-needle aspiration biopsy.

The authors report on the cytologic features of six cases of poorly differentiated "insular" carcinoma (IC) of the thyroid, a recently described variety of thyroid tumor intermediate between well-differentiated and anaplastic neoplasms. It is characterized by trabecular and/or alveolar growth patterns, merging with follicular areas, and by the absence of pleomorphism in the tumor cells. Fine-needle aspiration biopsy (FNAB) materials (both smears and cell-block preparations) from six patients were reviewed after the diagnosis of IC was confirmed on the surgical specimen. The following cytologic features were consistently found: high cellularity and necrotic background; low grade of atypia; trabeculae and/or clusters, possibly associated with microfollicles, of cells with poorly defined cytoplasm; and cytoplasmic vacuoles containing thyroglobulin. Nuclear inclusions and grooving of the nuclear surface were additional features. Preoperative diagnosis suggestive of IC might be of value for planning surgical treatment and subsequent therapy.

Adult↗

PubMed1990

Signet-ring cell carcinoid of the gallbladder.

A case of signet-ring cell carcinoid of the gallbladder is reported. The tumour diffusely infiltrated the gallbladder wall and extensively ulcerated the mucosa. Neoplastic nests were composed of numerous signet-ring cells mixed with clear endocrine cells. The latter expressed chromogranin A, gastrin and somatostatin and contained neurosecretory granules. The diagnostic problem of differentiating between signet-ring cell carcinomas and composite adenocarcinoma-carcinoid tumours is discussed.

Adenocarcinoma↗

PubMed1990

Chromogranin A and B gene expression in carcinomas of the breast. Correlation of immunocytochemical, immunoblot, and hybridization analyses.

Chromogranins (Cg) are regarded as specific neuroendocrine (NE) markers in cells and tumors. Expression of CgA and CgB genes has been demonstrated by correlative immunocytochemical, immunoblotting, in situ hybridization, and Northern blot procedures in seven argyrophilic breast carcinomas, while eight control cases of ductal carcinomas, not otherwise specified, were negative. A high degree of correlation was observed between the various techniques revealing CgA and/or CgB gene expression at different levels; minor discrepancies might be related to tumor heterogeneity or to technical factors. The present study, confirming previous investigations, establishes NE differentiation in a group of human breast cancers. The identification of this type of tumors, especially by testing chromogranin(s) production, appears to be of both biologic and clinical interest.

Biomarkers, Tumor↗

PubMed1990

Lack of cardiostimulant effects of bamifylline in in vitro and in vivo models.

The cardiac effects of bamifylline (Bamifix), an alkylxanthine derivative, were evaluated on in vivo and in vitro cardiac preparations and compared with those of theophylline and enprofylline. In isolated rat and guinea-pig right atria bamifylline, in contrast to the other xanthines, left the rate of contraction unchanged or reduced it. In isolated rat and guinea-pig left atria the compound induced only slight inotropic effects showing an intrinsic activity significantly lower than that of theophylline and enprofylline. In isolated rabbit papillary muscles bamifylline administration was without effect up to 10(-3) mol/l and decreased the contractile force at a higher concentration, while theophylline dose-dependently increased inotropism. Also in anaesthetized rabbits intravenous administration of bamifylline produced negative chronotropic and dromotropic effects that were associated, at the highest dose, with a reduction of myocardial contractility. Theophylline and enprofylline, at the same equimolar doses, induced positive chronotropic and inotropic effects. The results show that bamifylline is devoid of cardiostimulant effects in respect to other xanthine derivatives. Moreover, they suggest that bamifylline acts on cardiac muscle by a mechanism, probably linked to the Ca+(+)-movements across the cardiac membrane, able to outweigh the effects due to its antiphosphodiesterase activity.

Animals↗

PubMed1989

Correlative study on neuro-endocrine differentiation and presence of somatostatin receptors in breast carcinomas.

To correlate the expression of neuro-endocrine (NE) markers with the presence of somatostatin receptors (SSR) in human breast cancer, a series of 100 cases was stained with the Grimelius silver procedure, by immunocytochemistry with specific NE markers (i.e., chromogranin A and B and synaptophysin) and by autoradiography for SSR. Nine cases were positive for at least one NE marker, while 4 cases were positive for all of them. SSR were detected in 17 cases, either with low (10 cases) or with high receptor density (7 cases). A highly significant correlation was established between the expression of NE markers and high SSR density. Our findings are additional evidence of the existence of a group of breast cancers showing morphological and cytochemical similarity with neuro-endocrine tumors present in other organs. The identification of this type of breast cancer is of biological and potential therapeutic interest.

Adult↗

PubMed1989

Ectopic endocrine pancreatic tumour simulating splenic angiosarcoma.

A case of ectopic endocrine pancreatic tumour that had developed within the spleen of a 46-year-old man is reported. The tumour was highly vascularized through the splenic artery, angiographically simulating an angiosarcoma. The histological pattern was typical of an endocrine tumour, and its nature was confirmed by a positivity for keratin, chromogranin A and somatostatin. Foci of atrophic pancreatic tissue were detected in the tumour capsule.

Choristoma↗

PubMed1989

Immunocytochemical detection of prostate-specific antigen (PSA) in skin adnexal and breast tissues and tumors.

Prostate Specific Antigen (PSA) is regarded as a specific marker of prostatic epithelium and has never been detected by immunocytochemistry in extra-prostatic tissues. The casual finding of a strong positivity for polyclonal antisera to PSA in a sweat gland carcinoma prompted a study on a series of skin adnexial and breast specimens (normal and neoplastic). Normal axillary and perineal apocrine sweat glands, some apocrine foci in fibrocystic breast disease and two sweat gland and two breast apocrine carcinomas were stained by several PSA antisera; a recently introduced monoclonal to PSA, however, was unreactive. These observations cast doubt on the specificity of PSA for prostatic epithelium, especially when polyclonal antisera are employed. Immunocytochemical reactions obtained with PSA, in the investigation of skin, lesions must be interpreted with caution and confirmed if necessary with monoclonals to PSA and with PAP.

Antigens, Neoplasm↗

PubMed1989

Neuroendocrine differentiation in carcinomas of the breast: a study of 51 cases.

A group of human breast carcinomas shows morphologic and histochemical evidence of neuroendocrine (NE) differentiation. This study presents a structural, immunologic, and electron microscopic analysis of 51 cases in order to establish positive criteria for identification of these tumors, their incidence, variants, and biological behavior. Argyrophilia (by the Grimelius procedure), presence of chromogranin A and/or B, and of synaptophysin are the most reliable histochemical features, correlating with the ultrastructural demonstration of dense-core secretory granules and of clear vesicles of the synaptic type. Structural features alone may be suggestive, but do not prove NE differentiation, which has to be established by additional techniques. Seven histologic types were identified, but those herein described as types A, B, and C, which show cohesive, mucoid, and mixed patterns, respectively, comprise the vast majority of the tumors. Rare NE carcinomas of the breast show structural similarities to Merkel cell and oat cell carcinomas, and behave as highly aggressive tumors. Type B (mucinous) tumors proved to be relatively indolent, while the most frequent types of endocrine tumors (types A and C) have an intermediate grade of malignancy. The analysis of a consecutive series of 100 cases of breast cancer indicates that about 8% of breast carcinomas display some degree of NE differentiation.

Adult↗

PubMed1988

A combined glucagonoma and VIPoma syndrome. First pathologic and clinical report.

We report a case of pancreatic tumour metastatic to the liver in a patient with insulin-treated diabetes, anaemia, cheilitis, necrolytic migratory erythema, hypokalemia and chronic watery diarrhea, a picture suggesting combined glucagonoma and VIPoma syndromes. Immunocytochemistry of a biopsied hepatic metastatic nodule revealed both glucagon and vasoactive intestinal peptide (VIP) positive cells. Increased plasma glucagon and VIP levels were detected (values of 900 pmol/l and 277 pmol/l respectively). This is the first reported case showing not only immunocytochemical, but also clinical evidence of the combined secretion of these hormones.

Adenoma, Islet Cell↗

PubMed1988

Hypophosphatemic oncogenic osteomalacia: report of three new cases.

Three cases of connective tissue tumors causing hypophosphatemic osteomalacia are reported and the literature is reviewed. In two of our patients the tumors were completely excised with total disappearance of the symptoms. In one case a total excision was not possible and the symptoms of this patient have not completely disappeared. The substance responsible for the syndrome has not been identified yet, but probably interferes with vitamin D renal hydroxylation, thus causing osteomalacia. As more than 30 per cent of cases of this condition have been reported in the last 5 years, it is suggested that these tumors are more frequent than previously believed.

Adult↗

PubMed1988

Dual secretory and myoepithelial differentiation in the transplantable R3230AC rat mammary carcinoma.

The hormone-responsive R3230AC mammary carcinoma, serially transplantable in Fisher rats, shows striking functional and morphological similarities to the normal mammary gland. We have studied its cellular composition by both light and electron microscopy, employing markers of myoepithelial and epithelial cells. We identified two cell types: the major cellular component corresponded to epithelial milk-protein secreting cells, while a second component showed immunocytochemical and ultrastructural characteristics of the myoepithelial cells. These cells were positive with a monoclonal antibody detecting alpha smooth muscle actin. The dual differentiation which normally occurs in breast ducts is therefore reproduced in a malignant experimental tumor. The coexistence of neoplastic cell populations, divergent in morphology and function, that persist in a tumor despite many transplant generations, leads to reconsideration of the relationship between cellular differentiation and malignant transformation.

Adenocarcinoma↗

PubMed1987

Chromogranin A and B and secretogranin II in bronchial and intestinal carcinoids.

Carcinoid tumours (bronchial and intestinal) were analyzed by immunoblotting for the presence of chromogranin A, B and secretogranin II. In all tumours an antigen corresponding in electrophoretic behaviour to adrenal chromogranin A was present. Lung carcinoids (3 out of 5) contained a relatively high concentration of a proteoglycan form of this antigen in addition. Chromogranin B was found in all tumours. In one and two dimensional immunoblotting it appeared identical to the corresponding adrenal antigen. Secretogranin II was also present, however concentrations (especially in intestinal carcinoids) were low and variable. Furthermore, in intestinal tumours it differed from the adrenal antigen by having a slightly higher molecular size and a more alkaline pI. Immunohistochemistry revealed that the tumour tissues stained positively for all three antigens. For secretogranin II the staining in intestinal tumours was relatively weak and quite variable. These results should provide a defined basis for immunohistochemical screening of carcinoids for the chromogranin/secretogranin antigens.

Bronchial Neoplasms↗

PubMed1987

Endocrine markers in argyrophilic carcinomas of the breast.

Argyrophilia in breast carcinomas is of uncertain significance. We tested a series of 20 cases of Grimelius-positive carcinomas with immunocytochemical markers of endocrine or exocrine differentiation. Fifty per cent of these tumors were positive, in a variable percentage of the neoplastic cells, with monoclonal antibodies against chromogranin, a specific marker of neuroendocrine differentiation. All cases were positive for neuron-specific enolase, but the significance and specificity of the reaction remain doubtful. The apparent positivity for alpha-lactalbumin, as found also by Clayton and coworkers, was found to be related to a contaminant, which is in fact also an endocrine marker. As with other types of breast carcinoma, all our cases were positive for epithelial membrane antigen, evidence that argyrophilic breast carcinomas, and specifically the chromogranin-positive subgroup, should be interpreted as endocrine neoplasms displaying multidirectional differentiation.

Aged↗

PubMed1987

The interest of actin immunocytochemistry in diagnostic histopathology.

The immunohistochemical detection of different isoforms of actin provides useful data in the histopathological diagnosis of human tumours. The marked resistance of this protein to fixation and embedding procedures makes it a practical alternative to the ultrastructural search of microfilaments in routine tissue sections. Staining with monoclonal antibodies against alpha smooth muscle actin is helpful in the diagnosis of benign and malignant smooth muscle tumours and allows the differentiation of various types of spindle cell sarcomas. These antibodies are also useful in tracing the myoepithelial cells in normal and various pathological conditions of the breast and salivary glands. Skeletal muscle actin is a reliable marker in the diagnosis of rhabdomyosarcomas. Its use should be combined and complemented with other markers (i.e. desmin; foetal, slow and fast myosins; myoglobin) to monitor the degree of rhabdomyoblastic differentiation of the neoplastic cells in single cases, a parameter of potential prognostic value.

Actins↗