Expression of new phenotypic markers in cholangiocarcinoma and putative precursor lesions.
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Adenoma, Bile Duct↗
Biomedical subjects
G Coggi
Publications and source records attributed to G Coggi.
p53 immunoreactivity in inflammatory and neoplastic diseases of the uterine cervix.
Immunoreactivity for the tumour suppressor gene product p53 is commonly found in many different human malignancies and few premalignant lesions. Data on cervical neoplasms, however, are still lacking. We retrospectively investigated p53 immunoreactivity in 92 lesions of the uterine cervix, including 44 cases of chronic cervicitis, 29 squamous intraepithelial lesions (SILs), and 19 invasive carcinomas. p53 immunoreactivity, confined to the basal cell layer, was detected in 74 per cent of cases showing chronic cervicitis and in all cases with low-grade SILs. Conversely, suprabasal and/or diffuse p53 immunoreactivity was exclusively demonstrated in 25 per cent of high-grade SILs and in 74 per cent of invasive carcinomas. The results of this investigation document a high prevalence of p53-immunoreactive malignant tumours of the uterine cervix. In high-grade SILs, p53-immunoreactive cells paralleled the height of involvement by dysplastic changes within the squamous epithelium. A prolonged half-life of the protein is the most likely explanation for the occurrence of p53 immunoreactivity in neoplastic cells. The unexpected finding of p53-immunoreactive cells in inflammatory lesions, though possibly related to an increased proliferation rate of the basal cell compartment, requires further study and underlines the need for a careful approach to p53 immunocytochemistry.
Adenocarcinoma↗
Patterns of integrin common chain beta 1 and collagen IV immunoreactivity in hepatocellular carcinoma. Correlations with tumour growth rate, grade and size.
Thirty cases of hepatocellular carcinoma (HCC) were investigated immunocytochemically for expression of beta 1 integrin molecule and of collagen IV. Immunoreactivity was related to the tumour proliferation index, as detected by PCNA immunostaining, and to tumour size and grade. Membrane beta 1 integrin immunoreactivity was detected in the neoplastic cells of all cases, though two different staining patterns were clearly recognized. In 14 cases, beta 1 integrin immunoreactivity was confined to the cell-stroma interface, showing the same polarized pattern as the non-neoplastic cell counterpart. This staining pattern was associated significantly (P < 0.0001) with low PCNA labelling (i.e. less than 20 per cent of neoplastic cells showing nuclear immunostaining. Conversely, 16 cases showed non-polarized pericellular beta 1 integrin immunostaining. This staining pattern was significantly associated (P < 0.0001) with high PCNA labelling (more than 20 per cent of immunoreactive cells) and with tumour size greater than 4 cm in diameter (P < 0.0001). beta 1 Integrin, collagen IV, and PCNA immunoreactivities, however, did not correlate with the histological grade. The data emphasize that neoplastic progression of HCCs may be correlated with an aberrant expression of adhesion molecules and with a disruption of the collagen IV complement of basal membranes.
Antigens, Neoplasm↗
p53 accumulation in ovarian carcinomas and its prognostic implications.
Intranuclear p53 accumulation is a common finding in many different human tumors and is associated with a worse prognosis in breast, colon, and lung carcinomas. We immunostained a series of common epithelial ovarian cancers to assess (1) the prevalence of p53 accumulation and its clinicopathologic correlations, and (2) its prognostic implications. The study population comprised 98 patients (83 with follow-up data). A variable degree of p53 immunoreactivity, strictly confined to the neoplastic cells, was detected in 54 tumors (55%). Among these tumors there were 10 low expressors (1% to 10% immunoreactive tumor cells), 16 moderate expressors (10% to 50% immunoreactive cells), and 28 high expressors (> 50% immunoreactive cells). The prevalence of p53 immunoreactivity did not show any association with the histologic type of the tumors or with the disease stage at presentation. p53 Accumulation, however, was significantly more prevalent among poorly differentiated tumors (P = .0059, by analysis of variance). Life table analysis demonstrated that patients with tumors showing moderate and high p53 expression had worse disease-free and adjusted lengths of survival (P = .0011 and P = .0025, respectively, by Mantel-Cox). The patients with "early stage" disease (stages I and II) and p53 accumulation showed a trend toward shorter length of survival, but this did not reach statistical significance. However, patients with "advanced stage" disease (stages III and IV) and moderate or high p53 accumulation had a poorer prognosis (P = .0154 and P = .0171, for disease-free and adjusted length of survival, respectively). These results suggest that p53 accumulation occurs more frequently in tumors with aggressive behavior and that p53 immunoreactivity may have a prognostic role in certain subsets of patients with ovarian carcinoma.
Adult↗
Early changes in the calcitonin gene-related peptide (CGRP) content of pulmonary endocrine cells concomitant with vascular remodeling in the hypoxic rat.
Morphologic changes are reported to occur in rat lung vasculature after 3 days of hypoxia. We have previously shown that immunoreactivity for the vasodilator calcitonin gene-related peptide (CGRP) is increased in pulmonary endocrine cells by 7 days of hypoxia. Because these cells may be among the earliest mediators of the hypoxic response, we examined endocrine cell CGRP content in rat lung after 0, 2, 4, and 8 h and 1, 5, 10, 15, 20, 28, and 35 days of normobaric hypoxia, using optimal and supraoptimal dilutions of CGRP antibodies to demonstrate changes in CGRP immunoreactivity. This was compared with temporal changes in pulmonary vascular smooth muscle after 1, 5, and 20 days of hypoxia exposure by evaluating vascular immunoreactivity for alpha-smooth muscle actin (alpha-SM actin), platelet-derived growth factor (PDGF) beta-receptor, and proliferating cell nuclear antigen (PCNA). Significant increases in endocrine cell CGRP immunoreactivity were found after 4 h of hypoxia, and levels increased up to 1 day, followed by a decrease (at 5 days) and then a progressive increase up to 35 days. After 1 day of hypoxia, the number of vessels displaying immunoreactivity for alpha-SM actin, PDGF beta-receptor, and PCNA were also significantly increased. Whereas PDGF beta-receptor and PCNA returned to control values by day 20, alpha-SM actin reached a plateau that persisted until 20 days. The results indicate that modulation of endocrine cell CGRP content in response to hypoxia is rapid and characterized by a significant and persistent increase, paralleled by a proliferation of vascular cells leading to vascular muscularization.(ABSTRACT TRUNCATED AT 250 WORDS)
Actins↗
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↗
Abnormal p53 immunoreactivity and prognosis in node-negative breast carcinomas with long-term follow-up.
The expression of the p53 gene product was investigated immunocytochemically in a retrospective series of 164 formalin-fixed paraffin-embedded invasive breast carcinomas with pathologically proven negative lymph nodes. Overall, 78 tumors (48%) showed a variable degree of p53 immunoreactivity. Among these, 38 cases were low expressors (1-10% p53 immunoreactive tumor cells), 21 moderate expressors (10-50% immunoreactive cells) and 19 high expressors (> 50% immunoreactive cells). Abnormal p53 expression correlated significantly with tumor size, histological and nuclear grade, DNA ploidy, mitotic rate and proliferation index, and with the lack of estrogen receptors. Disease-free and adjusted survival analysis of the 124 node-negative patients with long term (more than 10 years) follow-up, however, did not reveal an independent prognostic role for p53 expression. These data suggest that the evaluation of p53 immunoreactivity may only play a role in a multiparametric prognostic assessment of node-negative breast carcinoma.
Biomarkers, Tumor↗
Liver-cell dysplasia and hepatocellular carcinoma.
Liver-cell dysplasia is a well known histological entity with preneoplastic significance in experimental hepatic carcinogenesis. However, while the association of liver-cell dysplasia with hepatitis B virus can be considered as established, it is still controversial whether this lesion represents a premalignant condition in cirrhotic patients. Efforts have been made to render its morphological assessment more reliable, but no firm conclusions can be drawn from the available clinical studies, which are mainly retrospective or based on autopsy series. Preliminary results from a prospective study argue that liver-cell dysplasia is associated with an increased risk to hepatocellular carcinoma. The emergence of liver-cell dysplasia as a preneoplastic lesion in cirrhotic patients will have some impact in the future on their management, including selection for closer monitoring in early detection of hepatocellular carcinoma and for liver transplantation.
Adult↗
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↗
Oncoprotein immunoreactivity in human endocrine tumours.
Abnormally expressed oncogenes are implicated in neoplastic transformation. We have investigated a series of endocrine tumours using immunocytochemistry as a first screening tool to detect oncogene expression. Paraffin sections of 44 pulmonary small cell carcinomas, 15 pulmonary atypical carcinoids, 12 bronchial carcinoids, 28 medullary thyroid carcinomas, 27 phaeochromocytomas, and 17 insulinomas were immunostained with antibodies to c-erbB-2, c-myc, L-myc, and N-myc. Diffuse immunoreactivity was detectable for c-erbB-2 in 8 out of 44 (18 per cent) pulmonary small cell carcinomas, 3 out of 15 (20 per cent) pulmonary atypical carcinoids, and 6 out of 27 (22 per cent) phaeochromocytomas; for c-myc in 18 out of 44 (41 per cent) pulmonary small cell carcinomas and 5 out of 15 (33 per cent) pulmonary atypical carcinoids; for N-myc in 6 out of 28 (21 per cent) medullary thyroid carcinomas; and for L-myc in 4 out of 27 (15 per cent) phaeochromocytomas. There was considerable intratumoral and intertumoral heterogeneity and, in each tumour group, no relationship was found between tumour pattern, mitotic index, and oncoprotein immunoreactivity. These results suggest that oncogene products are present in a proportion of endocrine tumours, and that specific oncoproteins seem to be related to tumour type but not to other histopathological findings. Thus, oncoprotein detection may be a useful tool for identifying subsets of endocrine tumours that are not otherwise recognizable morphologically.
Endocrine System Diseases↗
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↗
Use of monoclonal antibodies to human breast-tumor-associated antigens in the diagnosis of fine-needle aspirates of breast nodules: results of a multicenter study.
Fine-needle aspiration (FNA) cytology is being increasingly employed in conjunction with physical examination and mammography in the pre-surgical diagnosis of breast nodules. In the present study, we have submitted to multicenter validation an immunocytochemical test which employs monoclonal antibodies (MAbs) to breast-tumor-associated antigens (BTAA) for the diagnosis of breast cancer. The results of this analysis, which has evaluated 846 FNAs, show that the immunological test has a sensitivity of 88.62%, a specificity of 97.9% and an accuracy of 92.4%. The predictive value of a positive and a negative finding were 98.4% and 85.57% respectively. Comparison between the cytological and immunocytochemical diagnosis displayed a higher sensitivity, accuracy and predictive value of a negative result with the latter method (p less than 0.01). Our findings clearly indicate that immunocytochemical methods can complement and improve the diagnostic accuracy of FNA cytology of breast nodules.
Antibodies, Monoclonal↗
Cytokeratin-immunoreactive cells of human lymph nodes and spleen in normal and pathological conditions. An immunocytochemical study.
The occurrence and the distribution of cytokeratin (CK)-immunoreactive reticulum cells in a series of normal and pathological human lymph nodes and spleens are documented. The immunoreactive cells exhibit morphological and immunophenotypic features of so-called fibroblastic reticulum cells, with or without myoid differentiation. They invariably co-express vimentin and, to a lesser extent, desmin and muscle-specific actin isoforms. These CK-immunoreactive cells are apparently a normal subpopulation of reticulum cells, being detectable from the early stages of spleen and lymph node development. They are distributed mainly in the paracortical and medullary regions of the lymph nodes and at the periphery of the white pulp in the spleen. Their number and distribution are highly variable in different neoplastic and non-neoplastic pathological conditions but the changes are not disease specific. CK-immunoreactive reticulum cells are easily identifiable in both frozen and fixed lymphoid tissue and in cytological smears of fine-needle aspirates, provided that monoclonal antibodies whose spectrum of reactivity includes cytokeratins 8 and 18 are used. The awareness of the occurrence of CK-immunoreactive cells in normal lymphoid tissues is of particular relevance in the search for micrometastatic foci using anti-CK antibodies.
Adult↗
Choroid plexus papillomas.
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Cerebral Ventricle Neoplasms↗
Effectiveness and safety of the low-molecular-weight heparin CY 216 in the prevention of fatal pulmonary embolism and thromboembolic death in general surgery. A multicentre, double-blind, randomized, controlled clinical trial versus placebo (STEP). STEP Study Group.
Deep venous thrombosis is very frequent after general surgery, and its major complication, pulmonary embolism, is today the most frequent cause of postoperative death. The reduction of this cause of mortality is mainly based on its prevention rather than its therapy. This purpose was achieved by using physical and pharmacological means. During the past 15 years, low-dose heparin has been one of the most important means in the prevention of deep venous thrombosis, associated with early mobilization of surgical patients, but its actual efficacy against fatal pulmonary embolism was never statistically proved. In the early 80s new heparins became available, and their first experimental and clinical use demonstrated a longer half-life, a higher anti-Xa activity, and a lower haemorrhagic risk. On the basis of these data, we started a study in order to assess efficacy and tolerance of the new low-molecular-weight heparin CY 216 in preventing fatal pulmonary and thromboembolic death in patients undergoing general surgery. The study was designed as a multicentre, double-blind, randomized, controlled clinical trial versus placebo. A total of 4,498 patients, aged over 40 years undergoing general surgery, with anaesthesia lasting at least 45 min, were consecutively enrolled in the 18 centres which took part in the trial. 2,247 accounted for the CY-216-treated group and 2,251 for the placebo group. The patients received either subcutaneous injections of 0.3 ml of CY 216, equivalent to 7,500 anti-Xa units, or of 0.3 ml of a saline solution supplied in an identical form. The first dose was administered 2 h before surgery, the second 12 h later, and then once daily for at least 7 days. A post-mortem examination was carried out in every patient who died. The trial began in February 1986 and ended in June 1988. Statistical analysis showed that the two groups of patients were well matched for age, sex, type of disease, site and duration of operations, as well as for the incidence of risk factors which could predispose to the thromboembolic disease. Twenty-six deaths were recorded and validated. Eight (0.36%) belonged to the CY 216 group and 18 (0.80%) to the placebo group. In the CY 216 group, pulmonary embolism was the direct cause of death in 2 patients (0.09%), while the remaining 6 deaths could not be ascribed either directly or indirectly to thrombosis. In the placebo group, pulmonary embolism was the cause of death in 4 cases (0.18%; p less than 0.05) and contributed to death in 4.(ABSTRACT TRUNCATED AT 400 WORDS)
Aged↗
Beta-2-microglobulin amyloidosis and osteo-articular pathology of the uremic patient on regular dialysis.
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Amyloidosis↗
Adult nephroblastoma induced erythrocytosis. Report of a case and review of the literature.
We report a 32-year-old white male with nephroblastoma induced erythrocytosis. Serum erythropoietin levels were elevated preoperatively and normalized after surgical eradication of the renal mass causing the complete disappearance of the erythrocytosis. The erythropoietic hormone was demonstrated in the neoplastic mass confirming the nephroblastoma as the site of hormone synthesis. After surgery, the patient underwent a course of chemotherapy with actinomycin D (AMD) and vincristine (VCR) and is currently free of disease.
Adult↗
Immunocytochemical localization of progesterone receptors in endocrine cells of the human pancreas.
Progesterone receptors (PgR) have been immunocytochemically localized in the nuclei of several (40% to 75%) endocrine cells of the human pancreas and in a more variable number of neoplastic cells of 7 of 18 endocrine pancreatic tumors. Conversely the exocrine epithelial cells of the pancreas did not exhibit any PgR immunoreactivity in normal as well as in different pathologic conditions, including pancreatic adenocarcinomas. Estrogen receptors were not detected in any of the pancreatic samples investigated. Double immunocytochemical experiments have documented that PgR immunoreactivity in normal Langerhans islets is a consistent feature of most (75%) glucagon-producing A cells, of approximately 5% to 20% of insulin-producing B cells, and of a variable percentage of pancreatic polypeptide (PP)-producing cells, ranging from 5% to 70%. These figures were not affected by the sex, age, or underlying disease of the patients. The reported findings corroborate previous clinical and experimental evidence indicating that sex steroid hormones may have some regulatory effects on the functional activity of the endocrine pancreas.
Adolescent↗