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M Roncalli

Publications and source records attributed to M Roncalli.

At least 19 recordsLinked to original sources
PubMed1995

Liver cell dysplasia is a major risk factor for hepatocellular carcinoma in cirrhosis: a prospective study.

BACKGROUND/AIMS: In humans, the role of liver cell dysplasia as a preneoplastic lesion is still debated. A prospective, long-term, multicenter study was performed to establish whether liver cell dysplasia in cirrhosis is associated with an increased risk for hepatocellular carcinoma (HCC). METHODS: A cohort of 307 consecutive patients in whom liver cirrhosis was diagnosed by histology was investigated for development of HCC at 6-month intervals by ultrasonography and determination of alpha-fetoprotein levels. RESULTS: At enrollment, liver cell dysplasia was found in 75 patients (24%) and in 53% (P < 0.01) of those positive for hepatitis B surface antigen (HBsAg). After a mean follow-up of 46 months, HCC was detected in 45 cases, and it was significantly more frequent in patients with liver cell dysplasia (P < 0.01) and HBsAg-serum positivity (P < 0.01). Multivariate analysis showed that liver cell dysplasia was the most important risk factor correlated with HCC development. HBsAg positivity and age over 60 years were also independent risk factors for HCC. CONCLUSIONS: These results indicate that liver cell dysplasia is a major risk factor for HCC, and it should be looked for carefully by pathologists in liver biopsy specimens to identify patients requiring more intensive observation.

Aged↗
PubMed1995

Prognostic value of bcl-2 immunoreactivity in medullary thyroid carcinoma.

Bcl-2 expression has been evaluated immunocytochemically in a series of 33 medullary thyroid carcinomas (MTC) with long-term (mean, 10.3 years) follow-up. Twenty-six of 33 cases showed intense bcl-2 immunoreactivity in more than 25% neoplastic cells. Bcl-2 immunoreactivity did not correlate with several clinicopathologic parameters including sex and age of the patients, sporadic or familial disease, tumor size and stage, amount of amyloid stroma, and immunoreactivity for calcitonin, chromogranin A, proliferating cell nuclear antigen (PCNA), N-myc, and p53. Lack of bcl-2 immunoreactivity, however, correlated significantly (P = .0001) with a shorter survival. Indeed, the seven patients with tumors devoid of bcl-2 immunoreactivity all died of disease within 8 years from the diagnosis. In multivariate analysis, lack of bcl-2 immunoreactivity was an independent predictor of worse prognosis (P = .001 for disease-free survival and P = .0001 for overall survival). None of the other clinicopathologic variable investigated proved to be an independent prognostic parameter. It is concluded that down-regulation of bcl-2 expression in MTC may identify a subset of tumors with a more aggressive clinical course.

Adolescent↗
PubMed1995

p53 gene mutations, p53 protein accumulation and compartmentalization in colorectal adenocarcinoma.

p53 accumulation may occur in the nucleus and/or cytoplasm of neoplastic cells. Cytoplasmic accumulation has been reported to be an unfavorable, but not established, prognostic indicator in colorectal cancer. Different types of p53 intracellular compartmentalization could depend either on p53 gene mutations or on the interaction with p53 protein ligands. The purposes of our study were (1) to assess whether the different patterns of p53 accumulation are selectively associated with p53 mutations and (2) to evaluate the clinical significance of p53 mutations in colorectal carcinomas. We evaluated p53 gene mutations in colorectal carcinomas. We evaluated p53 gene mutations in exons 5 through 8, by polymerase chain reaction and single-strand conformation polymorphism analysis; p53 accumulation and intracellular compartmentalization were detected immunocytochemically with the antibodies PAb1801 and CM1. p53 mutations were found in 74 of 126 carcinomas (59%). Nuclear p53PAb1801 accumulation was associated with p53 gene mutations (P < 0.001) whereas cytoplasmic p53 CM1 accumulation was more likely to occur with the wild-type p53 gene (P = 0.048). Overall, 112 carcinomas (89%) displayed p53 gene mutations and/or p53 accumulations of any type. p53 mutations were not correlated with important clinicopathological parameters and were not related to patient survival. Our data suggest that mechanisms other than mutations may also play a role in inhibiting p53 tumor-suppressing functions in colorectal carcinomas. Cytoplasmic p53CM1 accumulation frequently does not depend on p53 mutations.

Adenocarcinoma↗
PubMed1994

Prognostic value of N-myc immunoreactivity in medullary thyroid carcinoma.

BACKGROUND: The analysis of N-myc expression in some neuroendocrine tumors has been reported to provide prognostic information. To the authors' knowledge, no attempts have been made thus far to correlate N-myc expression with the clinical outcome of medullary thyroid carcinoma (MTC). METHODS: N-myc gene product immunoreactivity was evaluated in 34 patients with MTC with long term follow-up, using the OA-11-803 polyclonal antiserum. The results were related to patient age and sex, sporadic or familial disease, tumor size, stage, growth rate (as determined by proliferating cell nuclear antigen [PCNA] immunostaining), and to clinical outcome. RESULTS: Patients harboring tumors with greater than 10% neoplastic cells immunoreactive to the N-myc antiserum (58% of the cases investigated) had significantly greater tumor size (P = 0.031) than patients with fewer or no N-myc immunoreactive cells. Deregulated expression of N-myc protein in tumor cells was not due to gene amplification, as demonstrated by multiplex polymerase chain reaction (PCR). In univariate analysis, patients with more than 10% immunoreactive neoplastic cells showed a significantly shorter disease free survival than did the remaining patients (P = 0.002). Among the other clinicopathologic parameters evaluated, male sex (P = 0.039) and sporadic disease (P = 0.035) also were associated with shorter disease free survival. In multivariate analysis, N-myc immunoreactivity (P = 0.039) and male sex (p = 0.050) retained a significant correlation with poor prognosis. CONCLUSIONS: Our results suggest that immunoreactivity to the N-myc antiserum, but not tumor growth fraction as evaluated by PCNA immunostaining, is a novel and useful adjunct to predict clinical behavior of MTC.

Adolescent↗
PubMed1994

Extracellular matrix proteins, integrin receptors (VLA-beta 1, VLA-alpha 2 and VLA-alpha 5) and growth fraction in atypical macroregenerative nodules of the liver: an immunocytochemical case study.

A case of cirrhotic liver harbouring three atypical macroregenerative nodules and an hepatocellular carcinoma was immunocytochemically investigated for the expression of VLA-beta 1, VLA-alpha 2 and VLA-alpha 5 integrins and for different extracellular matrix (ECM) components (collagen I, collagen IV, laminin, fibronectin and tenascin). In addition, the proliferative activity within the nodules was evaluated, using the MIB 1 monoclonal antibody (MAb). The cirrhotic liver disclosed a continuous staining pattern of the ECM proteins investigated, as well as a "sinusoidal" immunostaining of VLA-beta 1, VLA-alpha 2 and VLA-alpha 5. The macroregenerative nodules showed a discontinued immunoreactivity for ECM proteins while maintaining a VLA-beta 1 sinusoidal immunostaining, coupled with intercellular immunostaining. VLA-alpha 2 and VLA-alpha 5 expression was lacking. The growth fraction was low in both the above pathological conditions. The hepatocellular carcinoma was devoid of any ECM immunostaining. VLA-beta 1 immunoreactivity exhibited a honeycomb pattern of staining, whereas VLA alpha subunits were absent. MIB1 expression was high, being present in 30% of neoplastic nuclei. A possible relationship between atypical macroregenerative nodules and hepatocellular carcinoma is discussed.

Carcinoma, Hepatocellular↗
PubMed1994

C-myc and tumour suppressor gene product expression in developing and term human trophoblast.

Proliferation and differentiation of villous trophoblast during placental development, from an early stage to full-term, were investigated in routinely fixed and processed tissues, by means of the immunocytochemical localization of the cell cycle-related proto-oncogene c-myc and the p53 and retinoblastoma susceptibility (Rb) tumour-suppressor gene products. The proliferative activity of the trophoblast was determined using an antibody against proliferating cell nuclear antigen (PCNA) which stains all proliferating cells in paraffin-embedded tissues. Diffuse nuclear immunoreactivity for PCNA, c-myc and Rb gene products was a consistent finding in early cytotrophoblast; c-myc product expression was also detectable in both layers of mid-gestation trophoblast. Only scattered cytotrophoblastic nuclei of early gestational placenta displayed immunostaining for p53 gene product. In full-term placenta c-myc expression was undetectable while Rb gene product and PCNA immunoreactivity declined markedly. These results indicate that the expression of the above genes is spatio-temporally regulated during placental development. A potential involvement of the oncosuppressor gene products p53 and Rb in the control of trophoblastic proliferation and of c-myc in the control of both the proliferative and differentiation pathways of trophoblastic cells is suggested.

Cell Division↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
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

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↗
PubMed1991

Distribution of endothelin-like immunoreactivity and mRNA in the developing and adult human lung.

Localization and characterization of endothelin-producing cells in the developing (fetal and postnatal) and adult human lung was investigated using the technics of immunocytochemistry and in situ hybridization. Immunoreactivity for endothelin was seen mainly in pulmonary endocrine cells of developing human lung. Immunoreactivity was also seen in the airway epithelium in fewer cases (about 50%) of human adults. In situ hybridization with 35S- or 32P-labeled RNA probes complementary to endothelin-1, -2, and -3, showed that endothelin mRNAs were expressed in a number of cells that were in similar sites to endocrine cells. Immunocytochemistry and in situ hybridization employed on pairs of reverse-face serial sections showed the presence of endothelin immunoreactivity and mRNAs in the same endocrine cell. Correlative studies revealed that endothelin is co-localized with general endocrine markers (synaptophysin, chromogranin, protein gene product 9.5) and regulatory peptides (e.g., gastrin-releasing peptide). The density (cells/mm2) of endocrine cells containing immunoreactivity or mRNAs was highest during fetal life and started to decline before birth, and was minimal in adults. Endothelin-like immunoreactivity and mRNAs were also expressed in endothelial cells. From these results, it is concluded that endothelin is synthesized in endocrine cells of human lung and the change of developmental expression of this peptide suggests it may play a part in growth regulation in addition to its putative vasoconstrictor role in human lung.

Adult↗
PubMed1989

Abnormal DNA content in liver-cell dysplasia: a flow cytometric study.

To clarify the true nature of liver-cell dysplasia (LCD), a flow cytometric study has been performed. The DNA content of hepatocytes from 26 cases of cirrhosis with diffuse areas of LCD was investigated and compared to that of hepatocytes from 21 control patients with non-neoplastic and neoplastic liver conditions. Flow cytometric analysis was performed on propidium-stained nuclei from archival paraffin-embedded material. Analysis was directed to assessment of diploid as well as non-diploid peaks by calculation of DNA index (DI), using normal hepatocytes present in each sample as individual and specific references. Since only samples containing at least 10,000 nuclei were considered suitable for analysis, 4 of the 26 LCD cases were discarded. Eight of 22 LCD cases had an abnormal DNA content compared with 0/11 non-neoplastic cases (p less than 0.05) and 8/10 hepatocellular carcinomas (p less than 0.05). Non-neoplastic control cases displayed uniformly diploid stemlines whereas hepatocellular carcinomas had in 8/10 cases bimodal or trimodal populations. Thus, LCD is a heterogeneous lesion in terms of ploidy, and the abnormal DNA content observed in some cases supports its pre-neoplastic nature.

DNA↗
PubMed1989

Granulomatous and nongranulomatous lymphadenitis in sarcoidosis. An immunophenotypic study of seven cases.

Five cases of prescalenic granulomatous lymphadenitis (GL) and 2 cases of prescalenic nongranulomatous lymphadenitis (NGL) in 7 patients with sarcoidosis were studied with a large panel of monoclonal antibodies (anti-CD 1, CD 3, CD 4, CD 8, CD 14, CD 22, CD 25, HLA-DR, HLA-DQ, HNK-1, R 4/23). Immunopathologic analysis was performed by studying three different compartments of GL--granuloma, intergranulomatous area and sinuses--and of NGL--cortex, paracortex and sinuses. Intra- and intergranulomatous T lymphocytes were mainly of the CD 4 type in 4 out of 5 cases; in all the cases less than 25% of T lymphocytes stained also for CD 25. Epithelioid cells were HLA-DR+, HLA-DQ+, CD 14+ and, frequently, CD 1+ and CD 25+, the latter positivity being mainly restricted to the marginally located epithelioid cells. Sinuses were filled with T- and B- cells; sinusal histiocytes were HLA-DR+, HLA-DQ+, CD 14+ and, frequently, CD 1+ and CD 25+. In the cortex and paracortex of NGL, T-cell subsets paralleled the distribution and ratio observed in the intergranulomatous area of GL; furthermore the immunophenotype of NGL sinusal histiocytes roughly overlapped that observed in the same district of GL with a strong CD 1 and CD 25 positivity. These results, besides confirming the global imbalance of the CD 4/8 ratio in all the areas of GL, seem to demonstrate that the prevalence of CD 4+ or CD 8+ T-cells probably reflects different functional phases of the granulomatous process.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1988

A morphometric study of liver cell dysplasia.

Thirty-seven cases of cirrhosis with large liver cell dysplasia (LLCD) were evaluated by morphometric analysis and the results compared with those in 11 cases of hepatitis B surface antigen (HBsAg)-positive cirrhosis, 12 cases of cirrhosis with nodules of active regeneration, 15 cases of hepatocellular carcinomas, and 15 cases of inactive cirrhosis. The nuclear-cytoplasmic, nucleolar-cytoplasmic, and nucleolar-nuclear ratios of LLCD were significantly higher than those observed in all other nonneoplastic groups. Whereas the nuclear-cytoplasmic and nucleolar-cytoplasmic ratios of hepatocellular carcinoma cells were significantly higher than those measured in dysplastic cells, the latter had a nucleolar-nuclear ratio similar to that of neoplastic cells. These results show that, in contrast to previously accepted criteria, the nuclear-cytoplasmic ratio of LLCD is increased and that some morphometric features of LLCD are consistent with its supposed premalignant nature. The usefulness of a morphometric analysis in evaluating any group of abnormal-appearing hepatocytes is stressed.

Biopsy↗