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C Doglioni

Publications and source records attributed to C Doglioni.

At least 109 records · Page 6Linked to original sources
PubMed1993

Atypical lung carcinoid with GFAP immunoreactive cells.

A case of atypical carcinoid with peculiar histological and ultrastructural pattern and immunohistochemical phenotype is presented. The neoplasm is composed of three types of cells. Type 1 cells are small to medium sized, fusiform, with scarce cytoplasm and are arranged in fascicles. Type 2 cells are cuboidal and line acinar structures. Type 3 cells have more abundant eosinophilic cytoplasm, larger nuclei and are arranged in fascicles intersecting with fascicles of type 1 cells, and sometimes surround acinar structures. The three cell types are present both in the primary lesion and in its lymph node metastases. Immunohistochemistry demonstrates immunoreactivity of all cell types for general neuroendocrine markers. Cytokeratin immunoreactivity is more prominent in type 1 and 2 cells, and is only focally expressed in type 3 cells. Type 3 cells are also immunoreactive for glial fibrillary acidic protein (GFAP), alpha-actin, S-100 protein, vimentin. Electron microscopic examination confirms the neuroendocrine nature of the cells, and show that type 3 cells have prominent bundles of intermediate filaments, electron-dense granules and junctional complexes. To our knowledge, this is the first case of atypical lung carcinoid with GFAP immunoreactivity. The nature of type 3 GFAP positive cells is unclear. There are some clues pointing to their sustentacular nature, and other ones pointing to a myoepithelial origin, but the data are inconclusive. Type 3 cells may be the malignant counterpart of sustentacular cells seen in typical carcinoids, but their GFAP positivity and the presence of electron-dense granules are very unique features, which differentiates them from sustentacular cells. Alternatively, their unusual GFAP + immunohistochemical phenotype may be due to aberrant expression of cytoskeletal proteins.

Aged↗
PubMed1993

Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases.

The occasional finding within the gastric mucosa of unidentified epithelial cells with morphological features closely resembling those of pancreatic acinar cells has prompted us to investigate a retrospective series of 8,430 consecutive gastric biopsies and of 126 surgical specimens of gastric resection and total gastrectomy. The aims of the study were to morphologically and immunocytochemically characterize these cells, to define their actual prevalence in a large series of unselected cases, and to assess the clinicopathologic correlates of their occurrence. Pancreatic acinar-like cells characterized by abundant cytoplasm, which was acidophilic and finely granular in the apical and middle portions and basophilic in the basal compartment, have been identified in 101 cases (84 gastric biopsies and 17 gastrectomies). These cells, arranged in nests or in variably sized lobules among the gastric glands, were morphologically indistinguishable from pancreatic acinar cells, both by light and by electron microscopy. Furthermore, they were consistently immunoreactive for pancreatic lipase and trypsinogen and, in 75% of the cases, for pancreatic alpha-amylase. The appearance of these cells within the gastric mucosa was correlated significantly with chronic gastritis (p = 0.032) and with the simultaneous occurrence of intestinal and pyloric types of gastric metaplasia (p = 0.021). The findings indicate that this is a previously unrecognized pancreatic (acinar) metaplasia of the gastric mucosa, clinically and morphologically distinct from pancreatic heterotopia.

Adult↗
PubMed1993

p53 protein expression in non-neoplastic lesions and benign and malignant neoplasms of soft tissue.

Alterations of the p53 tumour suppressor gene, with consequent nuclear p53 protein accumulation, are among the most common genetic lesions in human neoplasms. In the present paper we show p53 immunoreactivity in 65% of malignant and 21% of intermediate malignancy soft tissue tumours, and in 48% of benign/reactive soft tissue lesions. p53 immunoreactivity of sarcomas can be interpreted as an indirect indication of a mutation of the corresponding p53 gene, suggesting that its alteration may have a role in their pathogenesis. Our data on p53 immunoreactivity in benign lesions of the soft tissues are among the first demonstrations of p53 over-expression in benign/reactive conditions. We cannot exclude mutations of the p53 gene in these cases, but it is difficult to sustain this hypothesis in reactive/pseudoneoplastic lesions. Alternatively p53 immunoreactivity in benign processes could be due to an increase in wild-type p53 as a result of different physiological mechanisms (cell type-specific p53 regulation, cell maturation, DNA repair). Our results do not indicate that immunohistochemical demonstration of p53 expression is a marker of malignancy in soft tissue tumours and therefore is of limited use in differential diagnosis. However, they suggest the need for further molecular genetic studies in order to elucidate the biological significance of the abnormal expression of p53 in benign soft tissue lesions.

Humans↗
PubMed1993

p53 Protein expression in nevi and melanomas.

p53 Protein immunohistochemical expression is a wide-spread feature of the malignant phenotype; most melanomas are reported as p53 positive, while nevi are reported as p53 negative. We investigate a series of 75 benign nevi and 47 melanomas (40 primary and seven metastatic) to evaluate their pattern of p53 immunoreactivity with a panel of specific antibodies (PAb1801, PAb240, DO7, and CM1) in view of a possible diagnostic role of p53 immunostaining. Our results demonstrate that 15% of nevi show p53 immunoreactive nuclei (usually in less than 1% of the cells) and that 30% of melanomas show p53 immunoreactive nuclei (one case with 20% immunoreactive cells, six cases with 1% to 5% positive cells, and four cases with less than 1% positive nuclei). p53 Positivity was seen also in basal and suprabasal keratinocytes. p53 Positivity in nevi is at variance with literature data supporting that nevi are p53 negative. p53 Positivity in nevi and in epidermis may be related to mechanisms of DNA repair, apoptosis, or to a specific phase of the cell cycle. In our series, p53 expression in melanomas is not as frequent as reported in the literature. Population-based differences or differences in case selection and sample handling may account for the above discrepancies. The demonstration of p53 positivity in benign skin lesions greatly hinders the possibility of a diagnostic use of p53 immunostaining in dermatopathology.

Adolescent↗
PubMed1992

Progesterone receptor immunoreactivity in pancreatic endocrine tumors. An immunocytochemical study of 156 neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin.

BACKGROUND: The immunoreactivity for progesterone receptors (PR) of the majority of endocrine cells of the human pancreas has prompted the authors to investigate if PR expression is maintained in pancreatic endocrine tumors and is correlated with the main clinicopathologic features of these neoplasms. Furthermore, the study has been extended to other neuroendocrine cells and tumors to determine whether PR immunoreactivity is a common feature of neuroendocrine cells and tumors other than those of the pancreas. METHODS: One hundred fifty six neuroendocrine tumors of the pancreas, gastrointestinal and respiratory tracts, and skin were immunostained for PR with three different monoclonal antibodies and for estrogen receptors (ER). Additional immunostainings for general neuroendocrine markers and for pancreatic hormones were performed in selected cases. RESULTS: Nuclear immunoreactivity for PR has been documented in the neoplastic cells of 56 (58.33%) of 96 pancreatic endocrine tumors. PR immunoreactivity was not influenced by the sex and age of the patients or the occurrence of a clinical syndrome related to inappropriate hormone secretion. Tumors synthesizing pancreatic polypeptide, glucagon, and insulin expressed PR in higher percentages (80%, 75%, and 66%, respectively) than those producing other pancreatic hormones or those that were not functioning. Irrespective of the functionally different tumor types, PR immunoreactivity showed a significant correlation (P = 0.0003) with the absence of metastases and the lack of tumor invasion of neighboring organs or of large vessels. As opposed to normal and neoplastic islet cells, the neuroendocrine cells and tumors of the gastrointestinal tract, respiratory tract, and skin did not show any PR immunoreactivity, with the single exception of a typical carcinoid tumor of the lung. ER were not identified in any pancreatic or extrapancreatic neuroendocrine cells or tumors. CONCLUSIONS: Nuclear PR are immunocytochemically detectable in most pancreatic endocrine tumors and are correlated significantly to the absence of pathologic evidence for malignancy. Conversely, PR expression has not been found in normal and neoplastic endocrine cells and tumors investigated.

Adenoma, Islet Cell↗
PubMed1992

p53 over-expression is an early event in the development of human squamous-cell carcinoma of the larynx: genetic and prognostic implications.

The tumor-suppressor protein p53 is over-expressed in a large fraction of squamous-cell carcinomas of the larynx (LSCCs). p53 overexpression is dependent upon the synthesis of mutated versions of the protein and has been associated with the malignant progression of certain tumor types. In order to examine the prognostic value of p53 immunodetection in LSCCs, we performed a retrospective analysis on a selected series of tumors, using the PAb 1801 and CM1 antibodies. No significant difference in the frequency of p53 over-expression was observed between tumors from patients with early relapse (67%) and those who had been disease-free for more than 5 years (84%). The lack of correlation of p53 immunoreactivity with clinical stage and differentiation grade of LSCCs, together with the coordinated expression of p53 in primary tumors and the corresponding lymph-node metastases, indicate that p53 over-expression is probably unrelated to the biological aggressiveness of these tumors. In addition, the detection of p53 immunostaining in pre-invasive areas as well as in preneoplastic lesions suggests that p53 abnormalities probably constitute a very early event in LSCC development.

Carcinoma in Situ↗
PubMed1992

High incidence of primary gastric lymphoma in northeastern Italy.

We previously noted an extraordinarily high number of cases of primary gastric lymphoma (PGL) in northeastern Italy. We have now formally compared the incidence in Feltre, Italy, with that in three similar communities in the UK. Each community has a stable population served by a single endoscopy unit and histopathology laboratory. There were 13 times more cases of PGL in Feltre in 1986-91 than in the UK communities (66 vs 5 per 100,000 per 5 years). The incidence of gastric adenocarcinoma was also substantially higher in Feltre than in the UK (270 vs an average of 82 per 100,000 per 5 years), as was the prevalence of gastritis associated with Helicobacter pylori infection (87% of 1343 gastric biopsy samples in 1991).

Humans↗
PubMed1992

Detection of calbindin-D immunoreactivity in human follicular dendritic cells.

The calcium-binding protein calbindin-D (28 kD) has been analysed immunohistochemically in different human lymphoid tissues. Combined immunohistochemical staining showed that calbindin-D (28 kD) is expressed by only a proportion of dendritic cells within the light zone of germinal centres, where antigens in the form of immune complexes are trapped and presented to B lymphocytes. All other cell types including macrophages, interdigitating cells, and various lymphocyte populations were negative. The expression of calbindin-D in this functionally relevant subset of follicular dendritic cells could have a role in the regulation of proliferation and selection of memory B-cells by modulating the concentration of calcium ions. Calbindin-D may be a useful marker for analysing in situ the phases of follicular development in different physiological and pathological conditions.

Calbindins↗
PubMed1992

Tumour suppressor gene products, proliferation, and differentiation markers in lung neuroendocrine neoplasms.

Typical carcinoid, atypical carcinoid, and small cell lung cancer (SCLC) fall within the spectrum of neuroendocrine lung neoplasms. This paper investigates the immunohistochemical expression of the products of tumour suppressor genes p53 and retinoblastoma (RB), together with proliferation (PCNA and Ki67) and neuroendocrine differentiation markers, in 14 typical carcinoids, ten atypical carcinoids, four borderline atypical carcinoid/SCLC, and 11 SCLC. We demonstrated that the phosphoprotein p53 and RB product can be immunolocalized on routine histological material. p53 protein was absent in all typical and atypical carcinoids, while it was abnormally expressed in eight SCLC and one borderline case. RB product was detected in all typical carcinoids and in two atypical carcinoids, while it was consistently absent in the other cases. PCNA-labelled cells were less than 4 per cent in typical carcinoids, about 40 per cent in atypical carcinoids, and over 70 per cent in SCLC. PCNA labelling index discriminates between typical and atypical carcinoids. Neuroendocrine differentiation was evaluated by a semi-quantitative method: a mean score value was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data was obtained, which was high in typical carcinoids, intermediate in atypical carcinoids, and low in SCLC. Our data show that the decrease in neuroendocrine features from typical carcinoid to SCLC is paralleled by an increase in proliferative activity and by an altered expression of tumour suppressor gene products. The above findings have diagnostic relevance.

Antigens, Neoplasm↗
PubMed1992

Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas.

Thirty-five endocrine tumors of the pancreas, 17 functioning and 18 nonfunctioning, were immunohistochemically studied for the expression of proliferating cell nuclear antigen (PCNA) using 19A2 and PC10 monoclonal antibodies. The proportion of PCNA-reactive cells (PCNA index) ranged from 0.2 to 27% in functioning tumors and from 0.1% to 55% in nonfunctioning tumors. PCNA index showed a statistically significant correlation with mitotic and Ki67 indexes. The median values of PCNA index identified three groups of patients: group A (PCNA < or = 2%), including 13 functioning and six nonfunctioning tumors; group B (PCNA between 2 and 5%), including three functioning and three nonfunctioning tumors; group C (PCNA > 5%), including one functioning and nine nonfunctioning tumors. All group A tumors were confined to the pancreas. In group B, the functioning tumors were limited to the pancreas, and the nonfunctioning tumors extended to extrapancreatic tissues. All group C patients had extrapancreatic extension of the disease. At follow-up, a PCNA index higher than 5% correlated to a decreased mean survival. Our data suggest that PCNA index is a reliable tool to assess the growth fraction, discern local from advanced diseases, and predict malignancy in pancreatic endocrine tumors.

Adolescent↗
PubMed1992

Low-grade gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT): a multifocal disease.

Gastrectomy specimens from five patients following gastroscopic biopsies which showed low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) were examined by serially sectioning and paraffin wax embedding using a 'swiss roll' technique. This procedure allowed the construction of a map of the specimen on which the distribution of the lymphoma could be plotted. In each case confluent lymphoma was identified. In addition small foci of lymphoma consisting of 1-4 lymphoid follicles surrounded by neoplastic centrocyte-like cells were seen. The positions of these 'micro-lymphomas' were plotted on the gastrectomy maps, showing multiple foci distributed throughout the gastric mucosa. The identification of these microscopic lesions may explain the development of local relapse, often after a long disease-free interval, in patients with gastric MALT lymphoma treated by partial gastrectomy where excision appears to have been complete. Patients treated in this way should, therefore, be followed-up indefinitely, with regular endoscopy and gastric biopsy, in order to identify early local disease relapse.

Adult↗
PubMed1992

Gastric giardiasis.

AIMS: To assess the prevalence of gastric giardiasis in patients undergoing upper gastrointestinal endoscopy, and to define the clinicopathological correlates of gastric Giardia lamblia infection. METHODS: Consecutive gastric biopsy specimens (n = 15,023) from 11,085 patients, taken at Feltre City Hospital (north eastern Italy) from January 1986 to December 1991, were histologically and immunocytochemically examined for the occurrence of G lamblia trophozoites. Three gastric biopsy specimens from patients harbouring G lamblia infection, who repeated endoscopy before treatment, were also examined electron microscopically. RESULTS: Forty one patients (0.37% of the population study) harboured gastric giardiasis. All patients underwent upper gastrointestinal endoscopy because of dyspepsia, epigastric pain, or abdominal distension. Only two patients had diarrhoea at the time of investigation. Giardiasis was clinically unsuspected in all cases, although the nine patients who also had duodenal biopsies performed had concomitant intestinal giardiasis. Gastric giardiasis was invariably associated with chronic atrophic gastritis. Intestinal metaplasia of the gastric mucosa and Helicobacter pylori infection were found in 32 and 37 of the 41 patients with gastric giardiasis, respectively. CONCLUSIONS: The invariable association of gastric giardiasis with chronic atrophic gastritis, most often showing intestinal metaplasia and H pylori infection, indicates that a decreased gastric acidity is a prerequisite for localisation of G lamblia to the gastric mucosa. Though its possible role as a gastric pathogen remains to be elucidated, these findings suggest that trophozoites should be carefully searched for when examining gastric biopsy specimens showing chronic atrophic gastritis.

Adult↗
PubMed1992

p53 protein expression in central nervous system neoplasms.

AIMS: To demonstrate, immunohistochemically, p53 protein expression in a selection of central nervous system tumours; to investigate the relation between p53 expression and that of the proliferation related antigen, PCNA. METHODS: Surgical specimens from 86 central nervous system tumours were routinely fixed, paraffin wax embedded, and immunostained with a monoclonal (PAb 1801) and a policlonal antibody (CM1) p53 protein and a monoclonal antibody against PCNA (PC10). Normal brain samples obtained at necropsy and 10 surgically obtained samples of gliotic brain parenchyma were also immunostained. RESULTS: p53 protein expression was observed in 35 of 86 brain tumours, suggesting frequent p53 gene mutation. p53 protein alterations were associated with all grades of malignancy in tumours displaying solely astrocytic differentiation, with the exception of pilocytic astrocytomas. In those showing oligodendroglial or ependymal differentiation they appeared to be restricted almost to only high grade lesions. No p53 immunoreactivity was observed in normal or gliotic brain tissue; p53 altered expression was not related to the percentage of PCNA labelled cells. CONCLUSIONS: The use of sophisticated gene amplification techniques or highly sensitive immunohistochemical methods might be useful in distinguishing between reactive and neoplastic astrocytic lesions, and in the identification of malignant progression in other non-astrocytic glial tumours. Tumours with very similar histogenetic differentiation features might actually be a genetically heterogeneous group with possible different clinical courses.

Antibodies, Monoclonal↗
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↗
PubMed1992

High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx.

A series of 58 primary human squamous cell carcinomas of the larynx (LSCCs) was examined for the expression of the p53 tumor-suppressor gene by a combined immunohistochemical and molecular approach. About 60% of the cases displayed nuclear p53 overexpression as revealed by immunostaining with PAb1801, PAb122 and PAb240 monoclonal antibodies. This phenomenon was associated with the presence of structural and/or transcriptional alterations of the p53 gene. Our results provide evidence that p53 abnormalities constitute the most frequent genetic alteration identified so far in LSCC and indicate that the abnormal accumulation of the protein correlates with the presence of p53-mutated versions. These findings, taken together with the peculiar biochemical properties of p53, support the hypothesis of a possible pathogenetic relationship between smoke carcinogen exposure and p53 inactivation in the development of this tumor type.

Antibodies, Monoclonal↗
PubMed1991

Glial fibrillary acidic protein immunoreactivity in normal and diseased human breast.

Immunostaining for glial fibrillary acidic protein (GFAP) identifies a minor subpopulation of immunoreactive myoepithelial cells in the normal resting human breast. The GFAP-immunoreactive cells also express a panel of myoepithelial cell markers, including cytokeratin 14 (CK 14), vimentin, smooth-muscle-specific actin isoforms, nerve growth factor receptor (NGFR) and common acute lymphoblastic leukaemia antigen (CALLA). The percentage of GFAP-immunoreactive myoepithelial cells is greatly increased in various neoplastic and non-neoplastic diseases of the breast, being highest in adenomyoepitheliomas. Furthermore, in all the instances of fibroadenoma, phyllodes tumour, epitheliosis and gynaecomastia, a variable number of epithelial cells also acquires immunoreactivity for GFAP, vimentin, CK 14, NGFR and, to a lesser extent, for CALLA. Conversely, GFAP immunoreactivity has never been encountered in the malignant cells of the different types of breast carcinoma. These findings suggest that the expression of GFAP might be a (possibly transient) feature of proliferating epithelial and myoepithelial cells in breast diseases other than carcinomas.

Actins↗