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M Barbareschi

Publications and source records attributed to M Barbareschi.

At least 73 records · Page 4Linked to original sources
PubMed1995

Prognostic value of intratumoral microvessel density, a measure of tumor angiogenesis, in node-negative breast carcinoma--results of a multiparametric study.

In the present study we update previous results on the prognostic value of intratumoral microvessel density (IMD), determined immunocytochemically using the monoclonal antibody CD-31 and a standard streptavidin-immunoperoxidase technique, published in the J Clin Oncol 12:454-466, 1994. This study was undertaken in those 211 node-negative breast cancer (NNBC) cases of that series of which we had pathological material available to determine all the prognostic indicators. The median period of follow-up has been extended to 78 and 80 months for relapse-free survival (RFS) and overall survival (OS), respectively, and new biological indicators (i.e. Ki-67 labeling and 67 kDa laminin receptor expression) were included in the analysis. The main results obtained are: i) a confirmation that IMD is not associated with the other biological markers studied, i.e. expression of p53 protein, c-erbB-2 protein, 67 kDa laminin receptor, and cell kinetics; IMD was weakly associated only with histological grade (p = 0.053); ii) IMD remains a highly significant prognostic factor for RFS and OS (p < 0.0001 and p = 0.018, respectively) in univariate analysis; iii) in multivariate analysis on RFS, IMD (likelihood ratio test (LRT) = 30.16; p < 0.0001), 67 kDa laminin receptor (LRT = 9.80; p = 0.0017), the IMD/67 kDa laminin receptor interaction (LRT = 8.62; p = 0.0033), tumor size (LRT = 8.56; p = 0.0034), and p53 protein (LRT = 4.96; p = 0.025) are significant and independent prognostic indicators. For OS, only tumor size (LRT = 8.34; p = 0.0038), menopausal status (LRT = 5.16; p = 0.023), p53 protein (LRT = 4.37; p = 0.036), and IMD (LRT = 4.05; p = 0.044) retain a significant and independent prognostic value. The results of this study confirm the prognostic importance on RFS of the variables previously tested, but not of peritumoral lymphatic vessel invasion. A novel finding is that 67 kDa laminin receptor and the IMD/67 kDa laminin receptor interaction are also significant and independent variables. For OS, the results confirm that both IMD and tumor size are significant and independent variables. With prolonged follow-up the novel finding that emerges is the prognostic importance of menopausal status and p53 protein. This new information could be useful for a more accurate selection of high-risk NNBC patients who require careful follow-up and may benefit from adjuvant therapy.

Analysis of Variance↗
PubMed1995

Diffuse partial woolly hair.

We report here a 14-year-old girl with diffuse partial woolly hair. The patient presented mild hair loss associated with the presence of fine, short and kinky hairs closely interspersed with the normal hair throughout the scalp. The pathology of the scalp revealed the presence of intermediate-sized hair follicles regularly intermingled with normal follicles in each follicular unit. The possibility that diffuse partial woolly hair may result from a progressive miniaturization of the hair follicles may explain the presence of evident hair thinning in several adult patients affected by this rare abnormality.

Adolescent↗
PubMed1995

[Lichenoid eruptions of the mouth mucosa induced by lithium carbonate. 2 cases].

INTRODUCTION: Several drugs can induce lichenoid lesions. CASE REPORT: We observed two cases of lichenoid lesions of the buccal mucosa due to lithium carbonate. Drug withdrawal caused clearing. DISCUSSION: These cases emphasize the rare nature of this complication. To date only one lichenoid stomatitis has been reported in the literature.

Adult↗
PubMed1995

Expression of bcl-2 protein predicts efficacy of adjuvant treatments in operable node-positive breast cancer.

The proto-oncogene bcl-2 encodes a protein that inhibits apoptosis, a common mechanism of cell death caused by hormone and chemotherapy. We have analyzed bcl-2 protein expression by immuno-cytochemistry in primary node-positive breast cancers in two groups of patients (for a total of 180 cases). One group received adjuvant hormone therapy, the other chemotherapy (cyclophosphamide, methotrexate, and fluorouracil), and both groups were followed for a median time of 63 months. We compared our findings with conventional clinicopathological indicators [menopausal status, number of axillary nodes, histological grade, tumor size and type, estrogen receptor (ER), and progesterone receptor] and with p53 protein expression. bcl-2 protein was present in 65% of the carcinomas (117/180) and it was significantly associated with ER and progesterone receptor and inversely associated with p53 in both the groups of patients treated with adjuvant chemotherapy and tamoxifen. In patients treated either with adjuvant chemotherapy or tamoxifen, relapse-free survival at 5 years was significantly better among patients with bcl-2-positive tumors than in those with bcl-2 negative ones (P = 0.05 and 0.02, respectively). As far as overall survival is concerned, patients with bcl-2-positive tumors had a significantly better outcome in the group treated with adjuvant chemotherapy (P = 0.03). Multivariate analyses were performed for the two treatment groups. In the group treated with tamoxifen, lack of expression of ER and of bcl-2 was the only significant and independent predictor for poor relapse-free survival (P < 0.01). A number of nodes above 3 was the only significant and independent predictor for poor overall survival (P < 0.01). In the cyclophosphamide-methotrexate-fluorouracil-treated group, bcl-2 absence was significant for poor overall survival (P = 0.02) as well as a number of nodes above 3 (P = 0.04) and a tumor size above 2 cm (P = 0.05). For poor relapse-free survival only a number of nodes above 3 (P < 0.01) and progesterone negativity (P = 0.02) were significant and independent predictors of a higher probability of relapse. Thus, in contrast to in vitro data on drug resistance, bcl-2 expression was associated with better outcomes in patients treated with hormone and chemotherapy. Overall, these results suggest that expression of bcl-2 protein and the number of metastatic lymph nodes are independent features predictive of clinical outcome in patients with node-positive breast cancer, irrespective of the type of adjuvant treatment. The determination of bcl-2 protein may prove to be a useful tool to distinguish patients for whom conventional forms of adjuvant therapy are beneficial from those with bcl-2 negative and ER-negative tumors for whom novel therapeutic strategies are needed.

Adult↗
PubMed1994

Abnormal expression of the p53-binding protein MDM2 in Hodgkin's disease.

The possible involvement of p53 tumor suppressor gene in the pathogenesis of Hodgkin's disease (HD) is suggested by the frequent finding of abnormal accumulation of p53 protein in the nuclei of Reed-Sternberg cells and their variants (H-RS) in a large proportion of cases. This finding, besides being consistent with the presence of p53 gene mutations, might represent a consequence of the inactivating interaction between p53 and p53-binding proteins such as the product of the MDM2 cellular oncogene. We have examined an unselected series of 77 HD cases of different histologic patterns for the expression of p53 and MDM2 proteins, using specific monoclonal antibodies and sensitive immunohistochemical techniques in single- and double-marker combination. In the large majority of cases (66/77), a variable proportion of H-RS cells expressed MDM2 that was strictly confined to the nuclei. Coexpression of both MDM2 and p53 was common in the same cells. The abnormal nuclear expression of p53 and MDM2 did not seem to correlate with the presence of Epstein-Barr virus infection, as shown by the results of LMP-1 antigen expression and EBER in situ hybridization analysis. Our data suggest that the abnormal accumulation of MDM2 and p53 proteins in HD might reflect a derangement of molecular mechanisms that could play a pathogenetic role in this disease.

Adolescent↗
PubMed1994

The prevalence of BCL-2 immunoreactivity in breast carcinomas and its clinicopathological correlates, with particular reference to oestrogen receptor status.

BCL-2 protein plays a pivotal role in overriding programmed cell death (apoptosis), thus favouring a prolonged survival of normal and neoplastic cells. Expression of the bcl-2 gene has been documented in some human tumours (non-Hodgkin's lymphomas and prostatic adenocarcinomas), but findings in breast carcinomas have not been reported. We have used the monoclonal antibody 124 to investigate BCL-2 expression in 212 breast carcinomas, and to correlate it with the oestrogen (ER), progesterone (PR) and epidermal growth factor receptor (EGFR) status, and with other clinicopathological variables including tumour type, grade, stage, growth fraction (as evaluated by Ki-67 immunostaining), and p53 accumulation. Of the 212 carcinomas, 173 (81.6%) exhibited BCL-2 immunoreactivity in more than 25% of the neoplastic cells. BCL-2 immunoreactivity was strongly correlated with ER and PR expression (P < 0.00001), with the lobular type (P = 0.012) and with better differentiated neoplasms (P = 0.00003), whereas it was inversely correlated with EGFR (P < 0.00001), p53 (P = 0.0004) and Ki-67 (P = 0.0002) immunoreactivities. No association was found with tumour stage (T and N categories). We conclude that bcl-2 expression in breast cancers is related to the oestrogen-dependent transcription pathway.

Adult↗
PubMed1994

p53 protein in low-grade astrocytomas: a study with long-term follow-up.

The immunohistochemical expression of p53 protein (p53) was examined in 52 patients out of a series of 66 patients with low-grade astrocytomas with long-term follow-up. All patients were also evaluated for several clinical and histological features, among which only preoperative Karnofsky score and the extent of surgery were statistically significant parameters to predict outcome on multivariate analysis. p53 accumulation was seen in 46.1% of patients, with a wide range of percentage of positive cells. Median survival for p53-positive and p53-negative patients was 41 and 37 months respectively. The survival curves of p53-positive and -negative patients were not statistically different. However, the curves showed a trend towards a more aggressive course in p53-positive patients beginning 3-4 years after surgery. Five years after diagnosis the survival estimate with the Kaplan-Meier method was 21.2% for patients with p53-positive tumours and 45.9% for patients with p53-negative tumours. This trend is not due to different distribution of major clinical prognostic factors (age, incomplete resection or Karnofsky status). The trend could be related to the time needed by the p53-positive clone to outgrow the rest of the p53-negative neoplastic cell population. This hypothesis is further supported by the fact that the five recurrences which were surgically removed (one anaplastic astrocytoma and four glioblastomas) derived from p53-positive tumours and were themselves intensely p53 positive.

Adolescent↗
PubMed1994

Quantitative growth fraction evaluation with MIB1 and Ki67 antibodies in breast carcinomas.

Ki67 and MIB1 monoclonal antibodies are directed against different epitopes of the same proliferation-related antigen. Whereas Ki67 works only on frozen sections, MIB1 may be used also on fixed sections. The authors immunostained a series of 40 breast carcinomas with MIB1 and Ki67 antibodies on serial frozen sections and on fixed material. The Ki67 labeling index (LI) was 12.9 +/- 8.9 and 12 (mean +/- SD and median, respectively). MIB1 LI was 21.2 +/- 11.9 and 19.5 on frozen sections and 24 +/- 15.2 and 21.5 on fixed sections (mean +/- SD and median, respectively). Ki67 LI and MIB1 LI on frozen and fixed sections were strictly correlated (P < .001). The results are in keeping with the reported coincidental nuclear staining pattern of Ki67 and MIB1, but the mean and median values of MIB1 LI are almost twice the values of Ki67 LI. The cut-off values to define high and low proliferative activity with the two antibodies are therefore different. The differences in immunolabeling may be due to better survival of the MIB1 epitope in freezing and acetone fixation or to differing accessibilities of the MIB1 and Ki67 epitopes during the cell cycle due to molecular conformational modifications. The MIB1 monoclonal antibody is a reasonable substitute for the Ki67 monoclonal antibody. The advantages of MIB1 immunostaining on paraffin sections include the feasibility of retrospective studies and of obtaining clear morphologic specimens that are optimal for use with computer-assisted image analysis systems. Our image-processing system allows automatic nuclear counting, detects positive nuclei and measures their staining intensity.

Adenocarcinoma↗
PubMed1994

Rapp-Hodgkin syndrome and AEC syndrome: are they the same entity?

Rapp-Hodgkin syndrome and AEC syndrome are two disorders in which ectodermal dysplasia and clefting are associated. Rapp-Hodgkin syndrome is an autosomal dominant condition characterized by cleft lip and palate, peculiar craniofacial features, and ectodermal dysplasia, consisting of abnormalities of teeth, hair, nails and sweating. AEC syndrome manifests the same defects plus ankyloblepharon and a higher frequency of scalp dermatitis. A child affected by ectodermal dysplasia associated with clefting, ankyloblepharon, severe scalp dermatitis, and the characteristic Rapp-Hodgkin facies is reported. The overlap between Rapp-Hodgkin syndrome and AEC syndrome is discussed. Critical review of both disorders suggest that AEC syndrome and Rapp-Hodgkin syndrome represent the same entity.

Cleft Palate↗
PubMed1994

Effects of naftifine and terbinafine, two allylamine antifungal drugs, on selected functions of human polymorphonuclear leukocytes.

Many antimycotic agents negatively affect the natural immune response. Typically, these drugs impair polymorphonuclear leukocyte (PMN) production of superoxide anion, chemotaxis, or the killing of pathogens. Allylamines are a new class of antimycotic compounds with a new mechanism of antifungal action, i.e., inhibition of the fungal squalene epoxidase. The trial that we describe aimed to evaluate the effects of two allylamines, terbinafine and naftifine, on selected functions of PMNs, i.e., superoxide anion production, chemotaxis, and killing of Candida albicans blastospores. Terbinafine and naftifine on their own did not affect superoxide anion production when they were added to PMNs. When PMNs were preincubated with allylamines and were then stimulated by N-formyl-Met-Leu-Phe or phorbol 12-myristate 13-acetate, superoxide anion production was increased (priming effect). Since intracellular free calcium (Ca2+i) is involved in the control of superoxide anion production, we evaluated the effects of the allylamines on the Ca2+i concentration ([Ca2+]i). In the presence of terbinafine or naftifine, the [Ca2+]i increased in a dose-dependent manner; the source of Ca2+i was not extracellular since it was not affected by extracellular calcium chelation with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In the presence of terbinafine or naftifine, chemotaxis of PMNs was not impaired. Terbinafine and naftifine slightly but significantly increased the killing of C. albicans blastospores (P < 0.05 at 10 and 100 microM). In conclusion, in contrast to imidazole-like drugs, the allylamine antimycotic compounds terbinafine and naftifine enhance selected functions of PMNs.

Allylamine↗
PubMed1994

Tumor microvessel density, p53 expression, tumor size, and peritumoral lymphatic vessel invasion are relevant prognostic markers in node-negative breast carcinoma.

PURPOSE: To determine the absolute and relative value of microvessel density (MVD), p53 and c-erbB-2 protein expression, peritumoral lymphatic vessel invasion (PLVI), and conventional prognosticators in predicting relapse-free (RFS) and overall survival (OS) rates in patients with node-negative breast carcinoma (NNBC). PATIENTS AND METHODS: We monitored 254 consecutive patients with NNBC for a median of 62 months. Intratumoral MVD was measured after microvessels were immunostained using anti-CD31 antibody. p53 and c-erbB-2 protein and hormone receptors were also determined immunocytochemically. Results were analyzed by both univariate and multivariate statistical analysis. RESULTS: Univariate analysis showed that MVD was significantly predictive of both RFS (odds ratio [OR], 8.30; P = .0001) and OS (OR, 4.50; P = .012) when tested as a continuous or dichotomous variable. Likewise, tumor size (OR, 3.16; P = .0012), PLVI (OR, 4.36; P = .0009), estrogen receptor (ER) status (OR, 2.35; P = .016), progesterone receptor (PR) status (OR, 2.00; P = .017), and expression of p53 protein (OR, 2.82; P = .004) were significantly associated with RFS. Tumor size (OR, 3.80; P = .0038) and expression of p53 protein (OR, 2.58; P = .024) were significantly associated with OS by univariate analysis. Multivariate analysis showed that MVD (P = .0004), p53 protein expression (P = .0063), tumor size (P = .0144), and PLVI (P = .0033) were all significant and independent prognostic factors for RFS. However, only tumor size (P = .004) and MVD (P = .047) were independent predictors for OS. c-erbB2 expression was not associated with outcome by either univariate or multivariate analysis. CONCLUSION: MVD, p53 expression, PLVI, and tumor size are independent prognostic indicators of recurrence, which are useful in selection of high-risk NNBC patients who may be eligible to receive adjuvant therapies.

Adult↗
PubMed1993

Atypical lung carcinoid with GFAP immunoreactive cells.

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

Aged↗
PubMed1993

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

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

Humans↗