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Biomedical subjects

G Bellezza

Publications and source records attributed to G Bellezza.

At least 19 recordsLinked to original sources

Low dentin matrix protein 1 expression correlates with skeletal metastases development in breast cancer patients and enhances cell migratory capacity in vitro.

Small integrin-binding ligand N-linked glycoproteins (SIBLINGs) constitute a family of extracellular matrix proteins involved in bone homeostasis. Their pattern of expression has been primarily reported in bone and tooth and, more recently, in several cancer types. Dentin matrix protein 1 (DMP1), a SIBLING family member, expression was investigated by immunohistochemistry in a retrospective series of 148 primary human breast cancers. Correlations between DMP1 expression levels in the tumors and clinicopathologic features, bone metastases development and relapse of the disease were examined. DMP1 was expressed by 63.5% of the breast tumors analyzed. Significant inverse associations were found between DMP1 expression levels and the size and grade of the tumors (both, P < 0.0001). High DMP1 expression levels in the primary breast lesions were associated with a lower risk of subsequent development of skeletal metastases (P = 0.009). Patients with tumors expressing high levels of DMP1 had a significantly higher disease-free survival rate than those with low DMP1-expressing tumors (P = 0.0062). When DMP1 expression was examined in breast cancer cell lines, we found that non invasive MCF-7 and T47-D cells expressed higher levels than highly invasive MDA-MB-231 and Hs578T cells. Moreover, the specific inhibition of DMP1 expression in MCF-7 cells using siRNAs promoted significantly their migratory capability. Our data implicate for the first time DMP1 expression in breast cancer progression and bone metastases development.

Adult↗

A population survival model for breast cancer.

Breast cancer is a major health problem, and disease control depends on an effective healthcare system. A registry-based tool to monitor the quality of breast cancer care could be useful. The aim of this study was to develop a population survival model for breast cancer based on the Nottingham Prognostic Model (NPM). To this end, 1452 cases of breast cancer diagnosed in the Umbria Region, Italy, during the period 1994-1996 were studied. An extensive search for routinely available variants in prognosis and treatment was performed. In about 80% of cases complete information on factors included in the NPM was available. The Cox model was used to assess the prognostic value of study factors. Nodal stage was the most important prognostic factor. In women who did not undergo axillary dissection (17%) the risk of death was twice that in women with no affected nodes, but they received chemotherapy with the same frequency. Radiotherapy was also less frequently used in this group. Grading was a significant prognostic factor only when women over 80 were excluded. Population survival models based on data from cancer registries may provide a tool that can be used to evaluate healthcare systems and the effectiveness of interventions. The inclusion of older women in our models decreased the significance of many established prognostic factors because of the frequency of incomplete evaluation and less aggressive treatment in these patients. Not undergoing surgical axillary dissection was associated with a worse prognosis and with less aggressive treatment.

Aged↗

Prognostic indexes in breast cancer: comparison of the Nottingham and Adelaide indexes.

The search for single independent prognostic factors in breast cancer has often produced conflicting results. Therefore, prognostic indexes have been compiled by combining several parameters. In this study we compare the Nottingham Prognostic Index (NPI), which is based on traditional prognostic factors (diameter of the neoplasm, lymph node status and histological grade) with the Adelaide Prognostic Index (API), which is based on the tumour diameter and two biological parameters: oestrogen receptors and cell kinetics. We considered 82 cases of breast cancer observed over the period 1987-1990 with a minimum follow-up of 60 months. The NPI gives a better definition of the prognostic profile for each patient. Our results indicate three prognostic groups (good, moderate, unfavourable), which differ with respect to disease-free survival (DFS; P=0.0024) and overall survival (OS; P=0.0033). In contrast, the API scores showed no significant correlation with OS or DFS. The use of prognostic indexes, especially when compiled using traditional parameters, is a useful aid to the clinician, since they can provide a reliable indication of how individual tumours will evolve.

Adult↗

Breast cancer in young women: clinicopathological features and biological specificity.

Literature data suggest that breast cancers occurring in young patients may be different from those arising in older women. In this study the clinicopathologic characteristics of 50 patients under 40 years of age were compared with those of patients aged over 60. Patients under 40 years old more frequently had a family history of breast cancer than did older patients (24% vs 17%) and had more often used oral contraceptives (29% vs 13%); on average they had experienced menarche 1 year earlier. For early onset breast carcinomas there was a higher frequency of grade 3 tumours (38% vs 17%) and oestrogen receptor negativity (46% vs 20%). In addition, in younger patients the carcinomas were mostly DNA aneuploid (78% vs 58%), with a higher proliferation rate (48% vs 26%) and more frequent c-erbB-2 overexpression (48% vs 26%) and p53 alteration (30% vs 8%). Our data demonstrate that breast cancers arising in young women have a significantly different biopathological profile from those in older patients, with a predominance of unfavourable prognostic parameters.

Adult↗

Evaluation of the prognostic role of vascular endothelial growth factor and microvessel density in stages I and II breast cancer patients.

In this study, we retrospectively evaluated the expression of vascular endothelial growth factor (VEGF) and microvessel density (MVD) in 228 and 213 specimens, respectively, from stages I and II breast cancer patients (pts) enrolled in a randomized phase III adjuvant chemotherapy trial comparing epirubicin to CMF, while tamoxifen was given to all postmenopausal pts. The expression of VEGF and MVD was assessed on tissue sections formalin-fixed and paraffin-embedded by immunohistochemical staining using anti-VEGF antibody of human origin and anti-CD34 monoclonal antibody. Univariate and multivariate analysis were performed using chi squared test, log-rank test and Cox's regression model. Sixty four of 228 pts were classified as VEGF positive (28%) with no significant difference in the two treatment arms. In 213 pts evaluated for CD34, 103 pts (48%) were classified as MVD high. No significant association between VEGF and MVD was found, and neither were they correlated with many known prognostic factors such as age, tumor size, nodal status, and histological grade. The only significant correlations observed were between VEGF and estrogen receptor (ER) status (p = 0.013) and between MVD and HER2 overexpression (p = 0.023). At a median follow up of 96 months VEGF and MVD were not correlated with relapse-free survival (RFS) and overall survival (OS) in all pts and in pts assigned to one of the two treatment arms. In conclusion, VEGF and MVD retrospectively evaluated, cannot be considered prognostic factors in node negative (N-) high risk and node positive (N+) breast cancer pts treated with two different regimens of adjuvant chemotherapy.

Adult↗

[Primary adrenal angiosarcoma].

Primary angiosarcomas of the adrenal gland are extremely rare neoplasms, first described in 1988. We report the twentieth case, incidentally discovered in a 60 year-old male. The main histological features were epithelioid appearance and immunohistochemical co-expression of endothelial markers and cytokeratin by neoplastic cells. The potential diagnostic pitfalls of these morphological characteristics are discussed. The patient underwent surgery and adjuvant chemotherapy and is free of tumour recurrence three years after surgery.

Adrenal Gland Neoplasms↗

Computer-assisted immunocytochemical determination of breast cancer steroid receptors. Frozen sections vs paraffin sections.

Previously we have demonstrated that determination of oestrogen (ER) and progesterone (PR) receptors by immunocytochemical assay (ICA) on frozen sections (FS) and cytological smears with image analysis is effective for evaluating steroid receptors. The aim of this study was to determine concordance between ER and PR assessed by ICA on FS and paraffin sections (PS) both evaluated by image analysis. There were 115 breast carcinomas selected. For all cases, ER and PR determination was performed on FS and PS. Computer-assisted image analysis was performed using CAS 200. Results were expressed as percent positive area of neoplastic nuclei compared with total nuclear area of the examined neoplastic cells. Good correlation was demonstrated for both ER (r=0.759; concordance=83.4%) and PR (r=0.800; concordance=87.8%). The unexpected relatively low concordance for ER led to further investigations. We divided the 115 cases in two groups. The first group included specimens from our hospital; the second group specimens from suburban hospitals. In the first group there was better correlation for both ER (r=0.897) and PR (r=0.915) with a concordance of 91.5% and 93.6%, respectively. In the second group, correlation was worse for both ER (r=0.724) and PR (r=0.708), with a concordance of 77.9% and 83.9% respectively. From analysis of discordant cases we conclude that reduction in correlation and concordance with increased false negative cases in group 2 are probably due to delayed fixation. Our data suggest that ICA with automated image analysis is efficient in evaluating ER and PR on paraffin section only when the tumour samples are correctly fixed.

Journal Article↗

[Synovial chondromatosis presenting as soft tissue mass].

Primary synovial chondromatosis is a rare condition characterized by the formation of hyaline cartilaginous nodules; pathogenesis is not fully understood. A soft tissue mass is an even more rare presentation of synovial chondromatosis. Histologically the condition shows some atypical features that suggest a malignant process. We describe a case of primary synovial chondromatosis presenting as soft tissue mass.

Aged↗

Biological prognostic factors for early stage completely resected non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: The different and unpredictable outcomes in early-stage non-small cell lung cancer patients requires urgent research concerning the biological pathway of this neoplasm. Our study investigated the frequency of expression and the clinicopathologic and prognostic significance of a series of biological markers in stage I and II resected non-small cell lung cancer. METHODS: A total of 99 cases of pathologic stage I and II were analyzed. The mean follow-up of surviving patients was 41 months. The expressions of the following biological markers were tested: bcl-2, p53, Ki-67, angiogenesis, and tumor vessel invasion. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biological markers using Cox's model for multivariate analysis. RESULTS: Tumoral vessel invasion was present in 22 (22%) pathologic samples, the angiogenesis mean value was 37 +/- 13, and median was 35; 13 (13%) patients showed positive immunostaining for bcl-2 oncoprotein. P53 oncoprotein expression was present in 48 patients (48.5%). All samples presented Ki-67 expression (mean value = 25.3 +/- 19.3, median = 20). The pathologic staging of the tumor was the most important independent prognostic factor for survival (P = 0.037) and for recurrence of disease (P = 0.040). Tumoral vessel invasion was the only marker with an independent predictive factor for survival and recurrence of disease in the group of patients without lymph node involvement (P = 0.02). CONCLUSION: Our data do not support a relevant prognostic role for p53, bcl-2, or Ki-67 immunohistochemical markers in non-small cell cancer. Tumor vessel invasion was an independent predictive factor of poor outcome in the group of patients without lymph node involvement. Pathological stage was confirmed as the most important independent prognostic factor.

Biomarkers, Tumor↗

Primary mucinous carcinoma of the skin.

Primary mucinous carcinomas of the skin are very rare. To date, 120 cases have been described in the literature. This tumor is a histologic subtype of sweat gland carcinoma. Because of the histopathologic appearance, primary mucinous carcinoma of the skin can be mistaken for metastasis from extracutaneous sites. We report on the cases of two elderly women with mucinous carcinomas arising in the scalp. Immunohistochemical staining of both tumors was positive for low-molecular-weight cytokeratin and epithelial membrane antigen. Carcinoembryonic antigen was positive in Case 2. Neuroendocrine features represented by neuron-enolase-specific positivity were also observed in both cases, and Grimelius and chromogranin A positivity were observed in Case 2. In both cases, there was strong positivity for estrogen receptor and progesterone receptor. Image analysis cytometry showed a diploid DNA content with a low rate of proliferative cells and negativity for p53 and c-erbB-2 proteins in agreement with the low aggressiveness of these neoplasms.

Adenocarcinoma, Mucinous↗

[Primitive angiitis of the central nervous system. An autopsy case report].

Primary angiitis of the central nervous system (PACNS) is a rare vasculitis limited to the leptomeningeal and intraparenchymal vessels. Histologically, the angiitis may be granulomatous with giant cells, necrotizing, or lymphocytic in character, and mixed morphologic types often occur. It is frequently fatal when the diagnosis is performed too late. We describe an autopsy case with multiple cerebral infarcts.

Aged↗

Combined overexpression of urokinase, urokinase receptor, and plasminogen activator inhibitor-1 is associated with breast cancer progression: an immunohistochemical comparison of normal, benign, and malignant breast tissues.

BACKGROUND: A strong positive correlation exists between the breast cancer tissue content of either urokinase-plasminogen activator (uPA) or plasminogen activator, inhibitor type I (PAI-1), quantified in the tissue extracts by immunoassays, and the survival of patients with breast cancer. Furthermore, several studies assign to the urokinase-type plasminogen activator receptor (uPAR) a pivotal role in triggering the proteolytic activity of the urokinase pathway involved in tumor stroma degradation, tumor spread and metastasis. However, the pattern of distribution of uPAR in normal and cancerous human tissue and the pattern of coexpression of activators and inhibitors that occurs in breast cancer tissues is not completely known. METHODS: The immunohistochemical localization of uPAR, uPA, tPA) and PAI-1 was evaluated by using the avidin-biotin immunoperoxidase technique and affinity-purified monoclonal antibodies from American Diagnostica Inc. Studies were performed in formalin fixed, paraffin-embedded tissue prepared from 23 surgically excised non-neoplastic breast tissues and 18 ductal breast carcinomas. RESULTS: While the expression of uPAR protein represents a constant feature of invasive ductal breast cancer, it was also observed in most of the breast tissue samples, including the normal breast tissues. The staining for uPAR was mainly localized on normal or tumoral epithelial cells, even if the co-expression of uPAR in stromal cells was frequently observed in adjacent slides. A semiquantitative analysis of immunohistochemical results showed that uPAR and PAI-1 were overexpressed in invasive breast cancer in comparison with normal and benign breast tissues. In addition, uPA was higher in both invasive breast carcinomas and benign breast lesions with respect to normal breast tissues. CONCLUSIONS: We showed that overexpression of uPAR, uPA, and its main inhibitor, PAI-1, is a constant feature of invasive ductal breast carcinomas. However, the expression of the above fibrinolytic reactants is not specific for breast cancer since positive staining for these molecules was frequently observed in benign breast lesions as well as in normal breast tissues. The combined increased expression of uPA and its cellular receptor, uPAR on the surface of tumor epithelial cells may account for the activation of the proteolytic system which occurs in breast cancer.

Breast↗

[Importance of cleansing in the topical treatment of skin lesions. A parallel study carried out in 20 patients and 30 rats].

There are frequent reports of the chronic nature of skin ulcers of varying etiology (burns, bedsores, wound diastasis, etc.); these heal with considerable difficulty probably due to problems related to the excessive use of disinfectants which, in spite of having a good bacterial action, interfere with re-epithelialisation processes. The aim of this study was to assess the value of simple wound cleansing instead of disinfection in those cases where there are no manifest signs of bacterial contamination. A widely sold solution, Katoderm (Devergè, Turin), was used in this study. The study was performed in two stages; the first in laboratory animals and the second in patients with small persistent lesions. The results of the study carried out in rats showed a significant prolongation of healing time in the group treated with polyvinylpyrrolidone-iodine compared to those in which lesions were only cleansed with Katoderm. The results of the clinical study also highlighted the faster speed of healing in patients treated with cleansing alone.

Administration, Topical↗