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Biomedical subjects

P Bevilacqua

Publications and source records attributed to P Bevilacqua.

At least 37 records · Page 2Linked to original sources

c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma--an immunocytochemical study.

The type I growth factor receptor family has been found to play an important role in the control of normal growth and differentiation. Moreover, the epidermal growth factor receptor and the c-erbB-2 oncogene seem to be implicated in the pathogenesis and behaviour of several cancers, including breast cancer. c-erbB-3 is a new member of the type I receptor family for which there is currently little information available on its expression in neoplastic tissues, and on its possible prognostic significance. This study was undertaken to define the prognostic value of c-erbB-3 expression in a series of node-negative breast cancer (NNBC) patients when compared, by multivariate analysis, with expression of the c-erbB-2 protein and conventional clinicopathological features. cerbB-3 was recognised by the novel monoclonal antibody RTJ1, whereas c-erbB-2 was detected by the polyclonal antibody 21N, using immunocytochemical methods. We found that overexpression of c-erbB-3 occurs frequently in NNBC. Overall, 138 of 212 carcinomas (65%) had some degree of membrane RTJ1 staining, and 28 (13%) showed strong and generalised positivity ( ). Twenty-four per cent of carcinomas had membrane 21N staining, and 12% presented strong and generalised positivity ( ). c-erbB-3 protein expression was significantly associated only with that of c-erbB-2 (P = 0.05), whereas 21N positivity was significantly associated with small tumour size (P = 0.02) and ductal histotype (P = 0.04). No significant correlation between expression of either receptor proteins or relapse-free survival was observed after a median follow-up of 63 months. Applying multivariate analysis, only tumour size approached significance. Our results indicate that analysis of expression of c-erbB-3 and c-erbB-2 alone do not seem to be useful in identifying patients with NNBC at different risk of relapse or death.

Adult↗

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↗

[The prognostic indicators of a favorable clinical evolution in dilated cardiomyopathy].

Improvement in cardiac function and clinical status has been described in subgroups of patients with dilated cardiomyopathy (DCM), but predictors of favourable outcome have not been unequivocally established. In 33 patients with DCM followed up for a mean of 23 months (range 3-68) a full non-invasive and invasive diagnostic work-up, including endomyocardial biopsy, was performed. At the end of the follow-up, 13 patients (39%; Group A) showed a significant improvement in their clinical status (> or = 1 gain in NYHA functional class) and cardiac function (> 0.10 increase in echocardiographic ejection fraction), while 20 (61%; Group B) either stabilized or deteriorated (5 died and 4 underwent successful heart transplantation). Clinical, hemodynamic and morphometric data of the 2 groups were compared. Only lower systemic vascular resistance (Group A 2,836 +/- 637 versus Group B 3,637 +/- 1113; p = 0.025) and higher prevalence of alcohol intake > 80 g/day (Group A 85% versus Group B 40%; p = 0.03) were significantly associated with improvement. Discriminant analysis utilizing these 2 variables along with cardiac index, mitral regurgitation, pulmonary resistance and cardiothoracic ratio reached a discriminant power of 72% (p = 0.0014). The above results suggest that, in our series, relatively simple data provide the most accurate assessment of prognosis. Yet, prediction of favourable versus unfavourable outcome remains uncertain, since an incorrect prognosis will be made in 28% of cases. Morphometric analysis of endomyocardial bioptic specimens does not provide significant prognostic information. The identification of a high alcohol intake has a clinical relevance, since abstention from alcoholic beverages is significantly associated with a favourable outcome in our patients.

Adult↗

Intratumoral microvessel density and p53 protein: correlation with metastasis in head-and-neck squamous-cell carcinoma.

Squamous-cell carcinoma of the head and neck includes a heterogeneous group of tumours of the upper air and food passages for which prognosis is difficult to assess. In fact, patients in comparable stages may have diverse clinical courses and responses to similar treatments. In order to better define the prognosis of each patient there is therefore a need to identify novel biological markers which reflect more accurately growth rate, progression and metastatic potential of each tumour. We assessed whether metastases correlate with microvessel counts (i.e. intratumoral vascularity) using the CD-31 monoclonal antibody (MAb) and p53 mutant protein expression, determined in the primary by immunocytochemical methods in 70 patients with locally advanced head and neck cancer. Patients were treated with concurrent chemo-radiotherapy; 50 of these presented loco-regional node metastasis at diagnosis whereas 3 cases, initially node-negative, developed distant metastasis during the period of observation. No feature was predictive for objective response to treatment. The overall mean and median blood vessel density at "hot spots" was 37.42 and 36, respectively, and 57% of the tumours expressed p53 mutant proteins. These 2 biological markers were significantly associated. Patients with metastases (loco-regional and distant) had a significantly higher mean blood-vessel density than those without tumour spread. Also, patients with p53-positive (+/++) tumours had a significantly higher incidence of metastasis than those with negative ones. Multivariate analysis showed that both vascularity and stage, but not p53 expression, are significant and independent predictors of metastasis in this series.

Adult↗

Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.

BACKGROUND: Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. PURPOSE: This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. METHODS: In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). RESULTS: There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. CONCLUSIONS: Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). IMPLICATIONS: Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.

Adult↗

Progesterone receptor determined by immunocytochemical and biochemical methods in human breast cancer.

Immunocytochemical assay (ICA) of the progesterone receptor (PgR) was performed on 152 patients with stage I-II breast cancer. We employed the rat monoclonal antibody KD-68 and a peroxidase/antiperoxidase displaying system. The results obtained by ICA (Pg(RICA)) were compared with those by the biochemical dextran-coated charcoal assay (PgRDCC). Comparing the two methods we found an overall agreement (accuracy) of 77.5%, a PgR(ICA) sensitivity of 83.5% and a specificity of 73%. Both methods were significantly associated with oestrogen receptor expression, detected by DCC (P less than 0.001 for PgRDCC and P = 0.0014 for PgR(ICA)). No significant association was found between PgR(ICA) or PgRDCC and the other clinicopathological features analysed. After a median follow-up of 36 months, the overall survival probability was 91% in PgRDCC-positive versus 81.5% in PgRDCC-negative patients (log-rank test, chi 2 = 0.91) compared to 87.5% in PgR(ICA)-positive versus 82% in PgR(ICA)-negative ones (log-rank test, chi 2 = 0.93). Disease-free survival probability was 74.5% in both PgRDCC-positive and PgRDCC-negative patients (log-rank test, chi 2 = 0.02) compared to 78% in PgR(ICA)-positive versus 71.5% in PgR(ICA)-negative cases (log-rank test, chi 2 = 0.37). The present study demonstrates that ICA is a reliable method to detect PgR, correlating well with the DCC assay. Moreover, the ICA assay seems to provide clinical information complementary to the biochemical method. The definition of its prognostic value in operable breast cancer needs additional studies, particularly in node-negative patients.

Adult↗

Peritumoral lymphatic vessel invasion compared with DNA ploidy, proliferative activity, and other pathologic features as prognostic indicators in operable breast cancer.

In 164 breast carcinomas the presence of peritumoral lymphatic vessel invasion (PLVI) was evaluated and correlated with other known indicators of prognosis and with the clinical outcome of the patients. Overall 22% of tumors were PLVI-positive. The presence of PLVI was significantly associated with axillary node involvement (p less than 0.0001) and tumor size (p = 0.005), and tended toward an association with grading (p = 0.065). No significant association was found between PLVI and steroid hormone receptors, DNA ploidy, or proliferative activity. Univariate analysis shows that peritumoral vessel invasion was significantly associated with a higher risk of recurrence (p = 0.012) and with a trend toward shorter survival (p = 0.074). Besides the presence of PLVI, prognosis was significantly worse also for patients with high proliferative aneuploid tumors and with axillary node metastases. Moreover, within the subsets of patients generally considered to have good prognosis, the presence of PLVI identified patients with a trend for higher risk such as those with PLVI-positive diploid tumors, PLVI-positive low-proliferative tumors, and PLVI-positive node-negative tumors. Adopting multivariate analysis, PLVI failed to retain prognostic importance when adjusted for node status, DNA ploidy, and proliferative activity. In conclusion, we found that the presence of PLVI has prognostic significance when singly evaluated. Multivariate analysis shows that PLVI is not an independent prognostic factor in stage I-II breast cancer.

Adult↗

In vitro restoration by thymulin of NK activity of cells from old mice.

Old mice show a reduced natural killer (NK) cell activity. Among the causes proposed to explain this defect, both intrinsic failure of NK cells or age-related alteration of microenvironmental factors relevant for NK function, have been taken into consideration. The findings reported in the present paper, demonstrate that thymic peptides, and in particular the facteur timique serique (FTS), more recently called thymulin (ZnFTS) in its zinc-bound form, whose production and activity is generally reduced in old age, is able, when administered in vitro, to restore the crippled NK cytotoxicity of spleen cells from old mice. Neither the zinc-unbound form of the hormone (FTS) nor zinc ions alone are effective. The action is exerted on the basal NK activity and not on IFN-boosted NK cytotoxicity, at variance with the restoration obtained in similar experimental conditions with thyroid hormones, thus suggesting that different mechanisms or maturative steps of NK cells are involved.

Aging↗

Value of epidermal growth factor receptor status compared with growth fraction and other factors for prognosis in early breast cancer.

The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein whose expression is important in the regulation of breast cancer cell growth. The relationship between EGFR status (determined by an immunocytochemical assay) and various prognostic factors was investigated in 164 primary breast cancers. Overall 56% of tumours were EGFR-positive and the expression of EGFR was unrelated to axillary node status, tumour size and histological grade; and it was poorly associated with the tumour proliferative activity measured by Ki-67 immuno-cytochemistry. The relapse-free survival (RFS) probability at 3-years was significantly worse for patients with EGFR positive tumours (P = 0.003) and for those whose Ki-67 score was > 7.5% (P = 0.0027), as well as in patients with axillary node involvement (P = 0.01) and with poorly differentiated tumours (P = 0.04). Immunocytochemical determination of EGFR and cell kinetics gave superimposable prognostic information for predicting RFS with odds ratios of 3.51, when evaluated singly. In our series of patients EGFR, Ki-67 and node status retain their prognostic value concerning RFS in multivariate analysis. The 3-year probability of overall survival (OS) was significantly better in node-negative patients (P = 0.04) and was similar in EGFR-positive and negative patients. In conclusion, EGFR status appears to be a significant and independent indicator of recurrence in human breast cancer and the concomitant measurement of the tumour proliferative activity seems to improve the selection of patients with different risks of recurrence.

Adult↗

Human breast cancer: prognostic significance of the c-erbB-2 oncoprotein compared with epidermal growth factor receptor, DNA ploidy, and conventional pathologic features.

PURPOSE: A study was undertaken to define the prognostic value of the expression of the c-erbB-2 oncoprotein in a series of breast cancer patients when compared by multivariate analysis with expression of the epidermal growth factor receptor (EGFR), DNA ploidy, and conventional clinicopathologic features. PATIENTS AND METHODS: Prognostic indicators were analyzed in 165 primary breast cancers. The c-erbB-2 oncoprotein was recognized by the polyclonal antibody 21N using an immunocytochemical method. Expression of the EGFR was stated immunocytochemically using the monoclonal antibody EGFR1. DNA ploidy was assessed in paraffin-embedded sections using a standard flow-cytometric method. RESULTS: Overall, 27% of carcinomas had membrane 21N-staining and were classified as c-erbB-2-positive. Overexpression of the c-erbB-2 oncoprotein was poorly associated with EGFR expression and the conventional pathologic features, and it was weakly associated with DNA ploidy and nodal status. Univariate analysis showed that c-erbB-2 expression, nodal status, DNA ploidy, and EGFR provided significant prognostic information concerning 4-year relapse-free survival (RFS) with the odds ratios (ORs) of not relapsing of 2.94, 2.83, 2.34, and 2.20, respectively. Regarding overall survival (OS) at 4 years, only nodal status and DNA ploidy had prognostic significance, with the ORs of not dying of 2.68 and 2.80, respectively. Applying multivariate analysis to RFS, 21N when adjusted for nodal status, EGFR, and DNA ploidy (full model) failed to retain prognostic value (P = .202), whereas nodal status was the most significant indicator of relapse (P = .027) followed by DNA ploidy (P = .056) and EGFR (P = .093). CONCLUSIONS: This study suggests that overexpression of the c-erbB-2 oncoprotein appears to be an important indicator of relapse in stage I-II breast cancer when singly evaluated. Multivariate analysis shows that the determination both of nodal status and DNA ploidy improves our ability to identify subsets of patients with different prognoses, and allows for a better selection of patients for systemic adjuvant treatments.

Adult↗

PC-10 antibody to proliferating cell nuclear antigen (PCNA) is not related to prognosis in human breast carcinoma.

The PC-10 monoclonal antibody to PCNA was employed to analyze proliferative grade in conventionally-formalin fixed, paraffin-embedded tumour samples of 162 patients with primary breast carcinoma. To perform the immunocytochemical method, sections were not heated, were de-waxed using alcohol, and then immersed in a phosphate-buffered saline solution and in methanol with 0.5% hydrogen peroxide to block endogenous peroxidase activity. Immunostaining was performed by a streptavidin-biotin peroxidase substrate. A semiquantitative scoring system was used to evaluate the fraction of nuclei that were PCNA-positive. The score ranged from 0% to 75% with a median value of 25%, mean of 27.8 +/- 1.5. PCNA staining was significantly associated with oestrogen receptor-negativity (p = 0.011) and correlated, but not at a statistically significant level, with tumour size (p = 0.08). No significant association was observed between PCNA and node status, grading, DNA ploidy, progesterone receptor or menopausal status. Prognostic indices such as number of positive lymph nodes and DNA ploidy were significantly associated with relapse-free survival (RFS) and overall survival (OS). No significant correlation between PCNA nuclear immunostaining and RFS or OS was observed after a median follow-up of 4 years. Our results indicate that analysis of PCNA alone does not seem to be a useful marker in identifying patients at different prognosis in human breast cancer.

Breast Neoplasms↗

Immunocytochemical determination of epidermal growth factor receptor with monoclonal EGFR1 antibody in primary breast cancer patients.

Epidermal growth factor (EGF) has been shown to be important in regulating the growth of breast cancer cells in vivo because of its mitogenic action on some breast cancer cell lines in vitro. Immunocytochemical analysis of EGF receptor (EGFr) was carried out on frozen sections in 134 primary breast cancer patients. Overall 68 of 134 (51%) of the tumors were EGFr positive. There was no correlation between EGFr positivity and menopausal status. Regarding the histopathological features, no significant correlations were observed between EGFr expression and tumor size, grading and lymph nodes status. Estrogen (ER) and progesterone (PgR) receptors were detected by an immunocytochemical assay and an equal distribution of EGFr was found regarding steroid hormonal receptors expression. Finally, there was only a positive trend between the proliferative activity of the tumors, as measured by Ki-67 antibody, and the amount of EGFr. Our results suggest the presence of a subclass of breast tumors, characterized by the absence of ER and/or PgR and the presence of EGFr, whose growth appears to be mediated by autocrine growth factors rather than by steroid hormones. The overall picture is that of an independent relationship between EGFr expression and the known prognostic factors in breast cancer.

Adult↗

Eruptive hidradenoma.

This case report emphasizes two clinical findings that aid in the diagnosis of eruptive hidradenoma. They are the predilection of the lesions for the anterior rather than posterior surface of the trunk and the presence of milialike inclusions within the papules. Eruptive hidradenomas are appendageal tumors that differentiate toward intraepidermal eccrine ducts and the milialike papules represent dilated cystic ductal structures. This patient had concomitant involvement of the eyelids, which has been observed in some, but not all, cases of eruptive hidradenoma.

Adenoma, Sweat Gland↗

Correlation of growth fraction by Ki-67 immunohistochemistry with histologic factors and hormone receptors in operable breast carcinoma.

Breast cancer tissue samples obtained from 147 Stage I and II patients were tested with the monoclonal antibody Ki-67 and avidin-biotin-peroxidase complex in frozen sections. The percentage of cells with nuclear staining ranged from 5% to 65%. The frequency of Ki-67 positivity was classified in five groups: 0% (45/147 = 31%); 5-9% (38/147 = 26%); 10-19% (15/147 = 10%); 20-39% (24/147 = 16%) and greater than or equal to 40% (25/147 = 17%). The mean value was 20%, median 18% with standard deviation of 14.5%. A significant positive correlation was observed between the presence of high Ki-67 nuclear staining rate with pathological tumor size (p = 0.003), histologic grading (p = 0.04), and axillary lymph node metastases (p = 0.009). An inverse significant correlation was found between Ki-67 and estrogen receptor expression (p less than 0.001). No correlation was observed with progesterone receptor expression or menopausal status. The overall picture is of an inverse relationship between high growth fraction determined with Ki-67 antibody and tumor differentiation parameters. These correlations confirm those already reported by thymidine labeling index and flow cytometry methods. The proliferative rate determined with Ki-67 antibody may provide information regarding cell kinetics of breast carcinoma, potentially useful in identifying patients with a different clinical course in order to improve the therapeutic approach, by a rapid, practical and easily performed immunohistochemical method.

Antibodies, Neoplasm↗

Immunocytochemical detection of progesterone receptor by monoclonal KD-68 antibody in operable breast cancer: correlations with biochemical assay, pathological features and cell proliferative rate.

A new immunocytochemical assay (ICA) for progesterone receptor (PgR), employing the rat monoclonal KD-68 antibody and a sensitive peroxidase-anti-peroxidase (PAP) technique as the displaying system, was performed in 129 human breast cancer specimens. PgR-ICA staining was almost all electively located in neoplastic cell nuclei with a substantial heterogeneity in distribution and intensity. To study the basic relationship of the results of the ICA method with the biochemical dextran-coated charcoal (DCC) assay we compared, in all the same specimens, the antibody nuclear staining with the PgR positivity by DCC (cut-off value of 10 fmol/mg of protein). We found an overall agreement of 77% between the two methods and a PgR-ICA sensitivity of 83% and a specificity of 72%, assuming that biochemical PgR is truth. PgR-ICA false-negative results were only nine out of 53 (17%); and false-positive were 21 out of 76 (28%). Using both methods no significant association was observed between PgR positivity with menopausal status, histological type, tumor size and lymph node status. The correlations between PgR expression and cell kinetics were assessed by an immunocytochemical method employing the monoclonal Ki-67 antibody. While a significant negative relationship was found between high Ki-67 score and PgR-ICA positivity (P less than 0.01) no correlation was found with DCC positivity. The present results demonstrate that ICA is a practical, reliable and inexpensive method with a good correlation to the conventional biochemical assay to determine the PgR status. Moreover, ICA recognizes PgR expression at the single cell level, thus providing additional information to the quantitative DCC assay that should improve the prognostic evaluation and the prediction of responsiveness to endocrine therapy in breast cancer.

Adult↗

Immunopathology of nasal polyps: an immunohistochemical approach.

We studied the mast cells and the T-lymphocyte subpopulations of four patients' nasal polyps using immunohistochemical procedures. The data showed that MC displayed IL2-receptor and that they were very often closely related to CD4+ and MHC class II-positive T-lymphocytes. CD8-positive T-cells represented only 10% to 15% of the whole lymphoid population and were not localized near mast cells. These findings suggest a possible role of cell-mediated immune reactions in the pathogenesis of nasal polyps.

Adult↗

Fatal asthma in a subject sensitized to toluene diisocyanate.

We report the case of a 43-yr-old car painter who died within 1 h of exposure to a polyurethane paint in the workplace. A diagnosis of asthma induced by toluene diisocyanate (TDI) had been established 6 yr before, when he underwent inhalation challenges with carbachol and with TDI. The subject had airway hyperresponsiveness to carbachol (PD20FEV1 carbachol = 0.32 mg; normal value greater than 1.0 mg) and developed an early and long-lasting asthmatic reaction after exposure to TDI in the laboratory. Although it was recommended that he change his job or stop using paints containing isocyanates, he continued to work as a car painter, taking antiasthmatic drugs both at work and at home to control asthma symptoms. On Monday, October 6, 1986, at 11:30 A. M., he developed a severe attack of asthma while he was mixing the 2 components of a polyurethane paint. Taken to hospital, he was dead on arrival. Autopsy showed no evidence of cardiac or brain disease; lungs were overinflated, the cut surface showed grey glistening mucous plugs in in the airways. Histologic examination showed denudation of airway epithelium and thickening of the basement membrane with infiltration of the lamina propria by polymorphonuclear leukocytes, mainly eosinophils, and diffuse mucous plugging of bronchioles. Bronchial smooth muscle appeared hyperplastic and disarrayed, and lung parenchyma showed focal areas of alveolar destruction adjacent to areas of perfectly intact alveolar walls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗