Search PubMed⌕ Search

Biomedical subjects

G Bussolati

Publications and source records attributed to G Bussolati.

At least 73 records · Page 4Linked to original sources
PubMed1999

Muscular cushions of the vessel wall at the periphery of thyroid nodules.

Insufficient vascular compliance might be the cause of regressive changes commonly observed within long-standing thyroid nodules. This hypothesis induced us to study the morphology of vessels at the periphery of nodular thyroid lesions. A series of 104 consecutive nodular goiters and 10 follicular adenomas were collected and stained for elastic fibers and alpha smooth muscle actin to study the morphology of vessel walls. Ninety carcinomas of different histologic type were reviewed as well. Cases of diffuse thyroid enlargement, such as Grave's disease and Hashimoto's thyroiditis, served as controls. In the peripheral zone of eight follicular adenomas and of about 50% of nodular goiters, muscular cushions, connected with the vessel walls, were merged within the fibrous tissue. Such structures were found only in five out of 90 cases (6%) of carcinomas and only when the tumors developed in a gland affected by long-standing nodular goiter. Muscular cushions were never observed in cases of diffuse thyroid enlargement. Such cushions were stained with anti-smooth muscle actin antibody and showed variable amount of elastic fibers, suggesting an origin either from arterial or vein walls. We suggest that the muscular cushions of the vessel walls are the result of nodular thyroid disease and that they should be considered real anatomical entities with a specific function as sphincteric structures.

Actins↗
PubMed1998

Presence and significance of oxytocin receptors in human neuroblastomas and glial tumors.

To determine whether oxytocin (OT) could be added to the list of growth factors acting on neoplastic cells of nervous origin, we investigated the presence of oxytocin receptors (OTR) in human primary neuroblastomas and glioblastomas and related cell lines. OTR were demonstrated both at mRNA level (using a RT-PCR procedure) and at protein level (using immunocytochemical and immunofluorescence procedures). In order to clarify whether OT exerts any biological effect on these tumors through OTR, we also studied cell proliferation in 3 human neuroblastoma cell lines (SK-N-SH, SH-SY5Y, IMR-32) and one human anaplastic astrocytoma cell line (MOG-G-UVW) treated with OT 1 nM to 100 nM for 48 and 96 hr. At these doses, a dose-dependent inhibitory effect on cell proliferation was demonstrated. This inhibition was accompanied by a significant increase in the intracellular concentration of cAMP, which we have reported to be the intracellular mediator of the OT anti-proliferative effect in breast-carcinoma cell lines. Our data indicate that specific OTR are present in human neuroblastomas and glioblastomas. Through these receptors, OT could inhibit cell proliferation and modulate tumor growth.

Brain Neoplasms↗
PubMed1998

Chromogranin A gene expression in non-small cell lung carcinomas.

Evidence for the existence of neuroendocrine (NE) differentiation in non-small cell lung carcinomas (NSCLCs) is at present based on histochemical, ultrastructural, and immunohistochemical data. The aim of this study was to investigate the extent of NE differentiation in NSCLCs as revealed by mRNA analysis. Different techniques including immunohistochemistry (IHC), northern blot analysis (NBA), and reverse transcriptase-polymerase chain reaction (RT-PCR) were employed in parallel to reveal the panendocrine marker chromogranin A (CgA). The data were related to pathological, immunocytochemical (PGP 9.5, synaptophysin, Leu-7 and neuron-specific enolase), and prognostic indicators. Forty surgically resected cases of NSCLC (24 squamous cell carcinomas, 12 ordinary type adenocarcinomas, 3 bronchiolo-alveolar carcinomas, and 1 anaplastic large cell carcinoma), in which fresh frozen material was available for mRNA analysis, were collected. CgA immunoreactivity was present in five cases (12.5 per cent), generally confined to a minority of the neoplastic cell population. By RT-PCR, CgA mRNA was found in 20 cases (50 per cent), including the five tumours positive by IHC. A statistically significant correlation was found between the two techniques. By NBA, no CgA mRNA expression was detected. Leu-7 immunoreactivity was present in 15 per cent of cases, NSE in 52.5 per cent, synaptophysin in 10 per cent, and PGP 9.5 in 82.5 per cent. In NSCLC, no correlations were found between CgA production, as detected by IHC or RT-PCR methods, and the histological type, stage, grade and proliferative activity of tumours, or the disease-free interval. It is concluded that CgA gene expression can be revealed in NSCLC at both mRNA and protein levels and that RT-PCR is a valuable tool for identifying NE differentiated NSCLCs. Our data suggest that NE differentiation does not represent an independent prognostic factor in surgically resected NSCLCs.

Adult↗
PubMed1998

Diagnostic cytological features of neuroendocrine differentiated carcinoma of the breast.

Neuroendocrine (NE) features characterize a minority of carcinomas of the breast corresponding to definite subtypes, which cover a wide spectrum of differentiation. Breast metastases from NE tumours of gastrointestinal origin are not rare, and to determine whether NE carcinomas in the breast could be differentiated from other tumours on fine needle aspiration (FNA) we analysed the cytological features of 13 primary NE breast carcinomas of different types (7 carcinoid-like, 5 mucinous and 1 solid spindle cell). Smears of carcinoid-like carcinomas showed specific features that made it possible to differentiate them from other primary tumours, but not from breast metastases of NE carcinomas. These features were: cell clusters with rigid borders, single cells with a plasmacytoid appearance and peripheral cytoplasmic granules evident on Giemsa staining and immunoreactive for chromogranin A. In mucinous NE carcinomas such granules were less apparent, and the cytological features could have been mistaken for those of fibroadenomas, as in the case of non-NE mucinous carcinomas. The solid spindle cell type showed noncohesive fusiform cells and moderate nuclear pleomorphism, a pattern similar to that of atypical carcinoids of the lung.

Adenocarcinoma, Mucinous↗
PubMed1998

Malignant phyllodes tumor of breast with lung metastases mimicking the primary.

We report a case of recurrent malignant phyllodes tumor with liposarcomatous transformation metastasizing to the lung. The unusual feature of this case was that the metastases reproduced the primary tumor and contained ductal structures and elements of sarcoma. The origin of the ductal structures in the lung metastases was confirmed to be from the phyllodes tumor, on the basis of their immunophenotype. The epithelial cells were positive for steroid receptors and GCDFP-15, and the myoepithelial cells were positive for anti-smooth-muscle-specific proteins. We also reevaluated by immunohistochemistry a case of phyllodes tumor previously published by West et al., allegedly containing epithelial structures of supposed breast origin within lung metastases. The epithelial component was shown to consist of entrapped alveolar lining cells.

Actins↗
PubMed1998

Neuroendocrine differentiation in Ewing's sarcomas and primitive neuroectodermal tumors revealed by reverse transcriptase-polymerase chain reaction of chromogranin mRNA.

Ewing's sarcomas (ESs), primitive neuroectodermal tumors (PNETs), and neuroblastomas (NBs) are closely related neoplasms supposedly derived from the neural crest and belonging to the family of the small blue round cell tumors of infancy and childhood. We investigated the expression of the neuroendocrine and neuroectodermal markers chromogranin A (CgA) and secretogranin II (SgII) in ESs, PNETs, and NBs, both in primitive tumors (five, nine, and four cases, respectively) and in established cell lines (three ES and two PNET cell lines). Different technical approaches, namely immunohistochemistry, Northern blot analysis, and reverse transcriptase-polymerase chain reaction (RT-PCR) were used in parallel. Chromogranin A and secretogranin II production was constantly detectable in NBs by all procedures. CgA mRNA was detectable in most ESs and PNETs only by RT-PCR, whereas SgII mRNA was detectable in some ESs and PNETs by Northern blot analysis and in all tumors by RT-PCR. CgA and SgII proteins were never detectable by immunohistochemistry in ESs and PNETs. We conclude that neuroendocrine differentiation is shared by all three tumor entities, being more overt in NBs and rudimentary in ESs and PNETs; traces of chromogranin mRNA are detectable only by a highly sensitive RT-PCR procedure.

Adolescent↗
PubMed1998

Consistency achieved by 23 European pathologists in categorizing ductal carcinoma in situ of the breast using five classifications. European Commission Working Group on Breast Screening Pathology.

The increased detection of ductal carcinoma in situ (DCIS) by mammographic screening, the greater use of breast-conserving surgery, and the recognition that certain histological subtypes are associated with a greater risk of local recurrence has led to the formulation of several new classifications of DCIS in recent years. There are, however, no data concerning the degree of consistency with which these schemes can be applied by reasonable numbers of pathologists. Thirty-three cases of DCIS were thus examined by a working group of 23 European pathologists who categorized them using five recently published classifications: (1) that of the European Pathologists' Working Group based on differentiation (a combination of nuclear grade and cell polarization) with categories of poorly, intermediately, and well differentiated; (2) one based entirely on nuclear grade with categories of high, intermediate, and low, currently in use in the UK national and EC-funded breast screening programs; (3) the same classification in which only two categories, high nuclear grade and other, were used; (4) the Van Nuys system in which lesions are divided into high grade, non-high grade with necrosis and non-high grade without necrosis; and (5) a two-category classification based entirely on the presence or absence of comedo necrosis. Of the three systems with three categories, Van Nuys gave the highest overall kappa statistic of 0.42. Others gave similar values of 0.37 and 0.35 showing that assessing cell polarization in addition to nuclear grade neither improves nor worsens consistency. In all three systems, the middle category was associated with the lowest value for kappa. Of the two systems with two categories, that based on nuclear grade gave the highest overall kappa of 0.46 and that based on comedo necrosis the lowest of 0.34. The most robust histological features were thus high- and low-grade nuclei and necrosis as long as the latter did not involve the recognition of a comedo growth pattern. These values probably represent the maximum achievable, at least by reasonable numbers of pathologists in everyday practice. They are better than those previously reported for classification based entirely on architecture, but further improvement is needed.

Breast Neoplasms↗
PubMed1997

Oxytocin inhibits the proliferation of MDA-MB231 human breast-cancer cells via cyclic adenosine monophosphate and protein kinase A.

Oxytocin (OT) inhibits the proliferation of breast-cancer cells in vitro via a specific G-coupled receptor. To elucidate the intracellular mechanism involved in this biological effect, different G-coupled receptor mediators have been investigated in untreated and OT-treated MDA-MB231 breast-carcinoma cells. In these cells, after OT treatment, a significant cAMP increase was observed using a radioimmunoassay procedure, whereas the Ca2+ (determined with the fluorescent probe fura-2) and the inositol phosphate (determined after cell labeling with myo(2-(3)H)-inositol) concentrations were not modified, contrary to what has been observed in myometrial and myo-epithelial cells. The PKA inhibitor PKI (6-22) amide reverted the effect of OT, indicating that the anti-proliferative effect of the peptide is strictly related to the cAMP-PKA pathway. OT treatment did not modify tyrosine phosphorylation either. Our results indicate that in breast epithelial cells devoid of contractile activity, cAMP is the intracellular mediator of OT action, whereas the Ca2+-phosphoinositide system is not involved.

Breast Neoplasms↗
PubMed1997

Mixed medullary-follicular carcinoma of the thyroid. A morphological, immunohistochemical and in situ hybridization analysis of 11 cases.

Mixed medullary-follicular carcinomas (MMFC) of the thyroid are rare tumours showing the morphological and immunochemical properties of both parafollicular and follicular cell lineages. Their recognition is based on a classical WHO definition, although several other patterns have been described in recent years. We investigated 11 cases of MMFC by immunohistochemistry and in situ hybridization (ISH) to analyse the structural features, the immunophenotypic profile and the calcitonin (CT) and thyroglobulin (TG) gene expression of the neoplasm. Histologically, 10 cases had mixed parafollicular and follicular cell populations in the primary tumour and 1 only in the lymph node metastasis. All cases were immunoreactive for CT (in medullary areas) and TG (in follicular areas and also in the solid component of 8/11 cases). These findings were confirmed by ISH analysis. Combined ISH and immunostaining showed that most cases had separate CT and TG gene expression, although rare cells with concurrent CT and TG gene expression were identified in 2 tumours. We conclude that (a) MMFC display heterogeneous morphological patterns and are a special type of thyroid tumour undergoing divergent differentiation; (b) in MMFC, CT and TG genes are generally not simultaneously expressed by the same cell, although dual expression of CT and TG was present in rare neoplastic elements; and (c) the origin of MMFC, whether they are derived from the ultimo-branchial body or result from neoplastic transformation of different cell populations following common oncogenic stimuli, is unclear.

Adenocarcinoma, Follicular↗
PubMed1997

Growth inhibition of DMBA-induced rat mammary carcinomas by UK 114.

A perchloric acid-soluble protein extracted from goat liver and designated as UK 114 is known to be expressed over the cell membrane of (some) human cancer cell lines. This protein is antigenic, and specific antibodies elicit complement-dependent cytolysis of neoplastic target cells. In this study we demonstrate that administration of UK 114, either pure or as a crude extract (designated UK 101), inhibits the growth of mammary carcinomas induced in female Sprague-Dawley rats by dimethylbenzanthracene (DMBA). The mechanism of the tumour inhibitory activity of UK 114 is probably related to induction of immunosurveillance.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Value of Ki-67 immunostaining in preoperative biopsies of carcinomas of the lung.

In lung carcinomas, the proliferative activity, as detected by Ki-67 antigen immunostaining of surgical specimens, is a valuable factor predicting clinical evolution and response to treatment. We investigated whether bronchial endoscopic and fine-needle aspiration (FNA) biopsies of lung carcinoma can provide a reliable estimation of the tumor proliferative fraction (TPF). In 66 resectable lung carcinomas, sections of preoperative bronchial or FNA biopsies and the corresponding surgical specimens were stained in parallel for Ki-67 using MIB-1 monoclonal. The mean TPF was 44.7% in the surgical specimens, 40.3% in bronchial biopsies, and 26.3% in FNAs. When the scores of biopsy and resected specimen of each individual tumor were compared, a significant correlation between the TPFs of preoperative and postoperative specimens was found (r = .79). In both biopsy and surgical specimens, a high TPF was associated with squamous cell carcinoma histological type and high-grade (poorly differentiated) tumors. In addition, a significantly (P < .05) lower disease-free interval was found in patients affected by highly proliferating tumors (irrespective of the tumor stage). We conclude that the proliferative activity of lung cancer can be reliably assessed in bronchial or FNA biopsies. This information could help to select chemotherapy protocols in nonresectable lung carcinomas.

Aged↗
PubMed1997

Retrieved endogenous biotin: a novel marker and a potential pitfall in diagnostic immunohistochemistry.

AIM: Antigen retrieval (AR) procedures are based on the effect of heating (by either microwave or pressure cooking treatments) on routinely fixed and paraffin embedded tissues. We observed that AR procedures restore the reactivity of endogenous biotin (EB) and report on the distribution of EB following AR in a series of routinely fixed and embedded tissues. METHODS AND RESULTS: Following pressure cooking or microwave treatments, a simple streptavidin-peroxidase staining revealed retrieved endogenous biotin (REB) in normal tissues (such as liver, kidney and adrenal cortex), in oxyphylic cells and in some tumours, especially in carcinomas of the kidney and of the adrenal cortex. In formalin-fixed (but not in alcohol-fixed) tissue sections, the heating procedures caused an intense and finely granular cytoplasmic reaction, following a routine streptavidin-conjugated peroxidase treatment. The staining was prevented by blocking of EB by a sequential avidin-biotin treatment. CONCLUSIONS: Retrieval of EB reactivity can cause pitfalls in diagnostic immunohistochemistry but, alternatively, it might also constitute a useful and novel diagnostic marker.

Antigens↗
PubMed1997

Immunophenotypic heterogeneity of hyalinizing trabecular tumours of the thyroid.

AIMS: We studied 12 cases of hyalinizing trabecular tumour of the thyroid gland (HTT) with the aim of reviewing the cytological, histological and immunophenotypic features and of investigating the relationships of HTT with other thyroid neoplasms. METHODS AND RESULTS: Eleven patients were female and one male, aged 8-74 years (median 58). Ten cases had a benign behaviour, while two cases were locally aggressive. Of the latter, one developed distant metastases and the other is a recent case. All patients are alive 6-311 months after diagnosis. Cytologically, HTT was characterized by hypercellular smears with aggregates of roundish cells having features of papillary carcinoma (nuclear grooves, vacuoles) and fragments of fibrous tissue. Histologically, prominent nesting, trabecular growth patterns and a hyaline stroma (partly positive for laminin and collagen type IV) were found. One case was associated with a papillary microcarcinoma. Two additional cases had extensive areas of papillary carcinoma. In one of these, hyalinized papillary stalks were observed. All tumours contained thyroglobulin but not calcitonin. High molecular weight cytokeratin (a marker of papillary carcinoma) was focally positive in 4/12 cases only and thyroperoxidase (a marker of follicular adenomas, but not of papillary carcinoma) was found in 3/12 cases. CONCLUSIONS: The immunophenotypic profile and the morphological features suggest that HTTs are an heterogeneous group of tumours, some of them probably representing variants of papillary carcinoma with hyalinized stroma.

Adenoma↗
PubMed1997

Tobacco smoke, recurrences, and p53/bcl-2 expression in bladder cancer.

Overexpression of p53 is considered to be predictive of mutations of the p53 gene. Exposure-specific mutations of the p53 gene have been described for cancers at different sites. An association between p53 mutation/overexpression and smoking has been described in early stage bladder cancer, but results were conflicting. We have conducted a study on 131 bladder cancer cases, considering p53 expression and smoking habits in an area where the use of air-cured tobacco, rich in carcinogenic arylamines, is common. The study suggests that the use of air-cured tobacco induces p53 overexpression (possibly via mutation) in early stage-low grade bladder cancer, more frequently than flue-cured tobacco (odds ratios = 3.4, 95% confidence intervals 0.9-13 in stage 1; odds ratios = 24, 95% confidence intervals 1.1-519 in stage 1, grade 1). However, all the excess associated with air-cured tobacco was concentrated in recurrences. When available, the biopsies of recurrent cases with early-stage disease were re-examined and all showed p53 expression at first diagnosis (with 10-50% of cells positive) (n = 5). It is hypothesized that exposure to tobacco-related chemicals increases the risk of recurrences via p53 overexpression/mutation. Expression of the bcl-2 gene was detected in only 2 out of 13 p53-positive smokers.

Adult↗