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G Bussolati

Publications and source records attributed to G Bussolati.

At least 37 records · Page 2Linked to original sources
PubMed2001

Progression from superficial to invasive carcinoma of the bladder: genetic evidence of either clonal heterogeneous events.

Until now, no definitive molecular evidence proving or disproving a true progression from superficial to invasive bladder tumors has been reported. A total of 36 lesions from 6 patients affected by invasive bladder cancer after multiple superficial recurrences were analyzed for loss of heterozygosity on 8 loci of chromosome 9 and 2 loci of chromosome 17. In addition, the clonal composition of the tumors from two female patients was examined using the human androgen receptor assay. Our data suggest that papillary bladder lesions can and sometimes do make a true progression into invasive life-threatening tumors; however, this progression is not an invariable sequence because it was definitely proven in 2 but not confirmed in 3 of the cases we examined.

Aged↗
PubMed2001

Clinical significance of neuroendocrine carcinoma of the breast.

BACKGROUND: Neuroendocrine (NE) carcinomas of the breast are defined by the diffuse expression of NE markers. This definition includes lesions with 'pure' NE phenotype as well as 'variants' which may co-express mucinous and/or apocrine phenotype. In the present work, the clinical significance of pure' NE differentiation in breast carcinoma and of its 'variants' will be analyzed. MATERIALS AND METHODS: Forty-three NE breast carcinomas immunocytochemically positive for chromogranins and/or synaptophysin in > or = 50% of cells were graded following the Elston and Ellis grading system for breast carcinomas. The production of mucin and the expressionof the apocrine marker Gross Cystic Disease Fluid Protein-15 (GCDFP-15) were correlated with the grade and the hormonal receptor status. The clinical outcome of patients was also analyzed. RESULTS: The histological grade highly influenced the clinical evolution of NE breast carcinomas. We confirmed that mucinous differentiation is an important indicator of low biological aggressiveness. Estrogen and progesterone receptor expression was also correlated with a better prognosis. Presence of androgen was correlated with the expression of GCDFP-15 in NE tumors. CONCLUSIONS: The histological grade overcomes the immunophenotype in determining the prognosis of NE differentiated carcinomas of the breast. Co-expression of exocrine products in such tumors is related to hormone dependency.

Apolipoproteins↗
PubMed2001

Biological relevance of oxytocin and oxytocin receptors in cancer cells and primary tumors.

For a long time, the hypothalamic nonapeptide oxytocin (OT) is known to play a crucial role in many reproductive and behavioral functions. In recent years, a new biological effect of OT has been identified in neoplastic pathology. In this context, OT acts as a growth regulator. through the activation of specific G-coupled transmembrane receptors (OTR). In vitro, an antiproliferative effect of OT was demonstrated in neoplastic cells of either epithelial (mammary and endometrial) or nervous or bone origin, all expressing OTR. Furthermore, the growth-inhibiting effect of OT was also tested and confirmed in mouse and rat mammary carcinomas in vivo. In neoplastic cells from another OT target tissue, trophoblast, the OT effect was to promote proliferation, the opposite of what previously observed in all the other neoplastic OT responsive cells. The signal transduction involved in the OT biological effect was different in OT growth-inhibited or growth-stimulated cells. In the former, the OT effect was mediated by the activation of the cAMP-PKA pathway, a non-conventional OT signaling, whereas in the latter by the increase of intracellular calcium and tyrosine phosphorylation, which are the 'classical' OT transducers. The unexpected role of OT (and OT analogues) in regulating cell proliferation, as well as the diffuse expression of OTR in neoplastic tissue of different origin, open new perspectives on the biological role of the OT-OTR system in cancer.

Animals↗
PubMed2001

34betaE12 cytokeratin immunodetection in the differential diagnosis of neuroendocrine carcinomas of the breast.

Neuroendocrine (NE) carcinomas of the breast share morphologic and immunohistochemical features with NE tumors of other sites, either resembling typical carcinoids or the highly aggressive small cell carcinoma. In addition, some mucinous carcinomas or solid/papillary carcinomas may show a major NE component. This is generally recognized by specific immunodetection of pan-endocrine markers, although this approach may fail to recognize NE tumors lacking immunoreactivity for some NE products, because the antigen is produced but not retained in the cytoplasm. It has recently been reported that high molecular weight (HMW) cytokeratin (CK), recognized by clone 34betaE12, immunostaining selectively labels non-NE carcinomas (squamous-cell and adenocarcinomas) of the aerodigestive tract and lung. The role of such CK immunodetection in the differential diagnosis of NE carcinoma of the breast was evaluated. Twenty-four cases of breast carcinomas having NE differentiation were selected. Twenty-four cases of non-NE invasive breast carcinomas served as controls. HMW CK immunoreactivity was found in all but one case of non-NE carcinomas, but in only two NE tumors (having scattered positive cells only). The authors conclude that in breast carcinomas the presence of HMW CK immunoreactivity favors the diagnosis of non-NE carcinoma, whereas its absence supports that of a NE tumor (either a carcinoid or a small cell carcinoma or a mucinous carcinoma). HMW CK can be added to the list of markers useful in the differential diagnosis of NE from non-NE tumors.

Biomarkers, Tumor↗
PubMed2001

Extensive DNA fragmentation in oxyphilic cell lesions of the thyroid.

The in situ end-labeling (ISEL) method demonstrates DNA fragmentation, commonly regarded as a marker of apoptosis. We investigated by the ISEL procedure a series of 52 thyroid lesions, including 24 lesions of mitochondrion-rich oxyphilic cells, both benign and malignant, and 28 non-oxyphilic control tumors. A high percentage of nuclear ISEL staining (approximating to 100% in most cases) was observed in the vast majority of oxyphilic cells from both adenomas and carcinomas, in the absence of morphological apoptotic changes and with no immunocytochemical evidence of caspase activation. This pattern of DNA fragmentation was not observed in non-oxyphilic lesions and was confirmed in total extracted DNA. Moreover, a peculiar cytoplasmic staining was also observed in oxyphilic cells from both benign and malignant lesions, probably related to abnormal fragmentation of mitochondrial DNA. Similar staining patterns were detected in oxyphilic cell tumors of other organs (parathyroids, salivary glands, and kidneys). These findings are consistent with an extensive DNA fragmentation peculiar to oxyphilic cells, which is not directly related to apoptosis and whose origin and biological significance are presently unknown.

Caspases↗
PubMed2001

Activation of functional oxytocin receptors stimulates cell proliferation in human trophoblast and choriocarcinoma cell lines.

Despite oxytocin receptors (OTR) being present in human chorio-decidual tissues, their expression and role in placental trophoblast cells in the context of tumor growth or physiological functions related to cell proliferation have never been examined. In the present study we demonstrate the presence and functionality of OTR in normal human trophoblast cell lines (ED77 and ED27) and a choriocarcinoma cell line (BeWo). RT-PCR and immunofluorescence analysis revealed the presence of OTR messenger RNA and protein in these cells. Binding studies using [(125)I]oxytocin ([(125)I]OT) antagonist confirmed the presence of specific binding sites in ED27, ED77, and BeWo cells. OTR functionality was demonstrated by measuring the OT-induced increase in the intracellular calcium concentrations. This effect was dose dependent and was blocked by the selective OT antagonist d(CH(2))(5)[Tyr(Me)(2),Thr(4), Tyr-NH(2)(9)]OVT (OT antagonist). Furthermore, two proteins with apparent molecular masses of 125 and 60 kDa became tyrosine phosphorylated in all of the cell lines after OT stimulation (and an additional protein of 45 kDa in BeWo choriocarcinoma cells), suggesting that this peptide can stimulate tyrosine kinase activity. Finally, we observed a dose-dependent OT stimulation of cell proliferation associated with OTR activation that was completely abolished by the selective OT antagonist. These findings provide the first evidence of the presence of functional OTR in normal trophoblast cell lines as well as in choriocarcinoma cells and show that a specific effect of OT on normal and neoplastic trophoblast is to promote cellular proliferation.

Calcium↗
PubMed2001

Classic and recent special stains used in differential diagnosis of endocrine tumors.

During the twentieth century, stains for endocrine cells and tumors were developed from empiric cytologic procedures aimed at modern cytochemical methods. Before the 1970s, endocrine stains were mainly based on silver reaction, although other reactions were also proposed; however, the chemical basis of most of these reactions is still unclear. The development of fluorescence procedures for detecting biogenic amines at the cellular level provided information about endocrine cell function of normal cells and related tumors. However, the application of immunocytochemical reactions brought greater and more definitive insights. Several immunocytochemical markers are now available. Some are specific for a definite cell type, while others detect endocrine differentiation in general. Some of these "pan-endocrine" markers are highly specific, and others are highly sensitive but less specific. They all play a definite role in diagnostic pathology. The use of molecular procedures to detect specific mRNA or genetic mutations of diagnostic interest in endocrine pathology should complement immunophenotyping, especially in some problematic fields, such as that of "poorly differentiated" tumors.

Antigens, Neoplasm↗
PubMed2001

[The role of the pathological anatomy museum: past glory, present crisis, and future prospects].

Scientific Museum and in particular pathology Museum were in the past an important landmark for Pathology and in general for Medicine. At present they are in a critical stage due to the technological progress, because they are considered by now obsolete compared to other didactic supports, so as for example CD-ROM or virtual presentations. In opposite these old collections are still very precious for Medicine, because they show old diseases, now disappeared or very rare, thanks to the therapeutic and diagnostic progresses. Furthermore they are very useful for teaching of Pathology to medical students and also to laboratory's technicians. The specimens may be used also for organisation of exhibitions, in graduate courses or medical updating courses, for a better popularisation of Anatomy or of some diseases of large environmental or social impact. For all these reasons we propose the creation of renewed museum structures and a protocol for the restoration of the specimens, which are often damaged owing to time and negligence.

Animals↗
PubMed2001

[Visceral pleural lipoma: description of a autopsy case].

Pleural lipomas are rare tumours, usually arising from the parietal pleura, which are often asymptomatic and observed incidentally. We describe the clinicopathological features of a case of lipoma arising from the visceral pleura, accidentally discovered in a 69-year-old ma, at autopsy. A review of the literature concerning pleural lipomas is also presented.

Adipocytes↗
PubMed2000

A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts oxytocin-mediated growth inhibition [corrected] of osteosarcoma cells.

We have previously described the presence of the functional plasminogen activator system on the surfaces of bone neoplastic cells and the fact that plasmin specifically cleaves bone matrix protein osteocalcin (OC). The cleavage of OC to NH2-midterminal (1-44) and COOH-terminal RFYGPV hexapeptide (44-49) proceeds with detachment of both products from bone mineral. Because the sequence of OC-derived hexapeptide (HP) is nearly identical to the E2 region of the oxytocin receptor (OTR), we set out to ascertain whether the HP interferes with the osteosarcoma (OS)-associated oxytocin (OT) system. We documented the presence and functional activity of OTRs in several OS cells by means of (a) OT-mediated inhibition of OS growth; (b) expression of OTR mRNA by means of reverse transcription-PCR; (c) immunofluorescence staining with IF3 monoclonal antibody specific for human OTR; and (d) saturation binding and Scatchard analysis of OT binding to the receptors of isolated membranes or intact OS cells. Although we could not demonstrate direct binding of HP to OT, the presence of HP in cultures of OS cells antagonizes the inhibitory effect of OT on these cells. Additionally, in competitive binding assays, the HP effectively competes with binding of OT to its cognate receptors. The results indicate the existence of an OTR/OT system in tumor cells of bone origin. Suggested plasminogen activator-OC-OTR/OT interactions may have an effect on the regulation of cell proliferation within the bone tissue as well as properties of the extracellular matrix surrounding the tumor foci in the bone.

Amino Acid Sequence↗
PubMed2000

Oxytocin receptors in human adenocarcinomas of the endometrium: presence and biological significance.

Oxytocin receptors (OTRs) are expressed in endometrial cells and oxytocin (OT) participates in endometrial functions. In cancers derived from other OT target tissues, such as breast and neural tissues, the expression of OTRs and the antiproliferative effect of OT on cancer cells has been previously observed. This study was therefore designed to search for OTR expression and the OT effect in endometrial carcinomas. To demonstrate the presence and the location of OTRs and OTR mRNA immunocytochemical, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) procedures were employed in a series of human adenocarcinomas of the endometrium. Using an anti-OTR monoclonal antibody (IF3), OTRs were demonstrated in the large majority of endometrial carcinomas (82%), with a pattern of positivity varying from diffuse to focal, according to tumour differentiation. The OTR gene was demonstrated in 78% of the cases by RT-PCR and its presence was confirmed in selected cases by ISH. Moreover, in a human endometrial carcinoma cell line (COLO 684) OTR was demonstrated by immunofluorescence and RT-PCR and it was observed that OT treatment (10(-11)-10(-7) M) significantly inhibited cell proliferation. Neither toxic effects nor apoptosis were induced by OT treatment. The addition of an inhibitor of protein kinase A (PKA) to the culture medium abolished the antiproliferative effect of OT, suggesting that cAMP via PKA could be the intracellular mediator of the OT effect, as previously observed in breast and neural tumours. In conclusion, this study presents evidence of OTR expression in human endometrial carcinomas and of an OT antiproliferative effect on human endometrial cancer cells in vitro. It is further suggested that OT and OTR may be involved in the regulation of endometrial cells, not only in physiological conditions but also in a neoplastic context.

Adenocarcinoma↗
PubMed2000

AgNOR quantity as a prognostic tool in hyperplastic and neoplastic parathyroid glands.

Prediction of evolution of secondary hyperplasia and tumours of the parathyroid glands is still a problem in histopathology. To assess whether the quantity of silver-stained nucleolar organiser region (AgNOR) proteins might be used as a prognostic tool in parathyroid pathology, a standardised AgNOR analysis has been performed on 19 cases of parathyroid hyperplasia caused by secondary hyperparathyroidism (PH), 8 cases of adenoma (PA) and 10 cases of carcinoma (PC). Clinico-pathological data and follow-up information were available. On formalin-fixed and paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the 1995 guidelines of the Committee on AgNOR Quantification. Then, the mean area (square micrometres) of AgNORs per nucleus (NORA) was evaluated by means of an image analyser and specific softwares. After testing the normal distribution of NORA values, statistical parametric tests were utilised; Kaplan-Meier and Cox multivariate analyses were also performed. In parathyroid lesions, a progressive increase of mean NORA values was observed from PH (2.895 microm2; SE 0.171) through PA (3.638 microm2; SE 0.125) to PC (4.701 microm2; SE 0.179); these differences were highly significant (P<0.001), although some degree of overlap was found among single NORA values. A significantly higher mean NORA value was revealed in PC with distant metastases than was noted in cases with no current clinical evidence of disease progression. Furthermore, a significantly (P<0.001) higher mean NORA value was encountered in the group of PH with recurrences (3.600 microm2; SE 0.106) than in nonrecurrent PH (2.261 microm2; SE 0.087). Multivariate analyses indicated that the NORA value was an independent prognostic parameter determining the risk of recurrence in PH. We suggest that AgNOR quantity may be a promising additional tool for predicting the biological behaviour of parathyroid lesions.

Adolescent↗
PubMed2000

Assessment of necrosis and hypoxia in ductal carcinoma in situ of the breast: basis for a new classification.

Modern classifications of ductal in situ carcinoma (DCIS) of the breast suffer from unsatisfactory reproducibility in inter-observer circulation analyses. Ducts in DCIS are markedly enlarged in the range of 360 microm in diameter. Since the diffusion of oxygen from peri-ductal vessels is limited to 100 microm, cells in the center of DCIS are poorly oxygenated and become either necrotic or remain hypoxic but viable. There is evidence that such alternative fate is dictated by the biological characteristics of the neoplastic cells. Therefore, determination of presence or absence of necrosis in ducts up to 360 microm in diameter might represent a simple, reproducible, and biologically sound criterion to classify DCIS. In the present work, following this criterion, we classified 32 cases of intra-ductal lesions as either "necrotic" or "hypoxic" and tested the reproducibility of such classification using K statistics. These cases had already been circulated among a group of European pathologists, who classified the lesions using five different classifications. The K statistics value obtained with the presently proposed system was extremely high (0.91). It remains to be established whether the classification "necrotic/hypoxic" withstands large inter-observer circulation analyses, whether it is predictive of the clinical evolution of DCIS, and whether it might constitute a reproducible basis for selecting appropriate treatments.

Breast Neoplasms↗
PubMed2000

Thyroglobulin mRNA expression helps to distinguish anaplastic carcinoma from angiosarcoma of the thyroid.

The existence of angiosarcoma (AS) of the thyroid has been a matter of debate for many years, because some authors believe that most if not all ASs are in fact "angiomatoid" anaplastic carcinomas (ACs). Immunohistochemistry alone was not successful in solving the problem, since cytokeratin expression is a known occurrence in AS. Therefore, we wanted to compare nine cases of AS with ten cases of AC, assessing whether thyroglobulin (TG) mRNA was still transcribed in undifferentiated tumors and could be helpful to distinguish AC from AS. The cases were analyzed for TG mRNA expression by means of radioactive in situ hybridization. The silver grains were counted using an automated device, and their amount was compared with that of stroma, background, and peritumoral thyroid. A weak signal was present in all AC but not in AS (mean counts 35.7 and 9.6 arbitrary units, respectively: P<0.01). In two cases of AC, residual areas of poorly differentiated insular carcinoma had a strong signal (similar to that of peritumoral thyroid). These findings further confirm that AC and AS of the thyroid are unrelated malignant tumors.

Adult↗
PubMed2000

Mammographically detected in situ lobular carcinomas of the breast.

We present ten cases of mammographically detected lobular carcinoma in situ (LCIS), involving a single area of variable size (up to a quadrant) in seven cases and the entire gland in three cases. Histologically, calcifications were associated with necrotic central areas within the in situ carcinomatous foci. Multiple foci of LCIS were observed in all five cases in which mastectomy had been performed. Cytologically, the lesions were characterized by a solid proliferation of round noncohesive cells with nuclei of intermediate size. Immunocytochemically, all cases were E-cadherin and p53 negative, and c-ErbB-2, GCDFP-15 and estrogen receptor positive. The proliferation index, evaluated with Ki67, was in the low range. Four cases were associated with foci of infiltrating lobular carcinoma (ILC). These findings contradict the commonly held opinion that LCIS is not mammographically detectable because of its lack of necrosis and calcification. This study documents the existence of a variant of LCIS exhibiting the mammographic features and central necrosis classically associated with ductal carcinoma in situ (DCIS), while retaining the spatial distribution, cytological composition and immunocytochemical features of lobular carcinoma.

Biomarkers, Tumor↗
PubMed2000

Causes of inconsistency in diagnosing and classifying intraductal proliferations of the breast. European Commission Working Group on Breast Screening Pathology.

It is now widely recognised that classifying ductal carcinoma in situ (DCIS) of the breast and diagnosing atypical ductal hyperplasia are associated with significant interobserver variation. Two possible reasons for this inconsistency are differences in the interpretation of specified histological features and field selection where morphology is heterogeneous. In order to investigate the relative contribution of these two factors to inconsistent interpretation of intraductal proliferations, histological sections of 32 lesions were sent to 23 European pathologists followed 3 years later by images of small parts of these sections. Kappa statistics for diagnosing hyperplasia of usual type, atypical ductal hyperplasia and ductal carcinoma in situ were 0.54, 0.35 and 0.78 for sections and 0.47, 0.29 and 0.78 for images, respectively, showing that most of the inconsistency is due to differences in morphological interpretation. Improvements can thus be expected only if diagnostic criteria or methodology are changed. In contrast, kappa for classifying DCIS by growth pattern was very low at 0.23 for sections and better at 0.47 for images, reflecting the widely recognised variation in the growth pattern of DCIS. Higher kappa statistics were obtained when any mention of an individual growth pattern was included in that category, thus allowing multiple categories per case; but kappa was still higher for images than sections. Classifying DCIS by nuclear grade gave kappa values of 0.36 for sections and 0.49 for images, indicating that intralesional heterogeneity has hitherto been underestimated as a cause of inconsistency in classifying DCIS by this method. More rigorous assessment of the proportions of the different nuclear grades present could lead to an improvement in consistency.

Breast↗