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F Pezzella

Publications and source records attributed to F Pezzella.

At least 19 recordsLinked to original sources
PubMed2003

Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer.

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P=0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (>60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.

Adult↗
PubMed2003

Vascular patterns in reactive lymphoid tissue and in non-Hodgkin's lymphoma.

The few studies published on angiogenesis in lymphoma have raised the question of whether or not microvessel density (MVD) is associated with more aggressive disease and have reported the observation that in follicular lymphomas, vessels are mature rather than immature. We investigated MVD and the vascular phenotype within follicular or diffuse large B-cell lymphomas, reactive nodes and tonsils. Vascular phenotype was defined by the expression or loss of reactivity to the antibody LH39 (detecting the LH39 laminin epitope of the basement membrane in mature vessels) and by detection of alpha V beta 3 (expressed on immature vessels). In reactive nodes and in follicular lymphomas, MVD was higher in the paracortex than in germinal centres or in neoplastic follicles. However, in neoplastic follicles an increase in alpha V beta 3-positive endothelium suggested the activation of an angiogenic pathway different from that present in the reactive follicles. In large B-cell lymphomas, MVD was higher than in reactive and neoplastic follicles but lower than in the reactive paracortex. The number of immature vessels (LH39 negative) and of alpha V beta 3-positive vessels was higher than in reactive lymph nodes and follicular lymphoma suggesting that a switch to a different angiogenic pathway has occurred. Finally, we have demonstrated that within reactive and neoplastic follicles vascular regression is occurring, perhaps constraining the growth of reactive follicles alongside other phenomena such as apoptosis. Vascular regression was previously believed to occur in adults only in ovarian and endometrial tissue. We conclude that different types of angiogenesis are present in follicular lymphomas and large B-cell lymphomas. This has implications for possible future therapies.

Basement Membrane↗
PubMed2003

p53 expression in normal paraffin-embedded tissue using different antibodies and antigen retrieval buffer systems.

AIMS: The study was undertaken to demonstrate wild-type p53 in normal paraffin-embedded tissues using two widely used antibodies, DO7 and 1801 and two different antigen retrieval buffer systems. METHODS AND RESULTS: Formalin-fixed paraffin-embedded normal tissue samples were obtained from the archives of the John Radcliffe Hospital, Oxford. Antigen retrieval was performed by microwaving using two different buffer systems: (i) the commercially available Dako target retrieval solution (Cat. no. 1699) (pH 9.8-9.9), (ii) freshly prepared buffer consisting of 0.1 m EDTA with 0.1% Tween pH 6.0, and (iii) freshly prepared buffer consisting of 0.1 m EDTA with 0.1% Tween pH 8.0. Staining was performed with DO7 and 1801 antibodies using the Dako Envision kit (peroxidase/DAB). DO7 antibody elicited strong nuclear staining in the mucosal cells of the small and large intestine, lymphoid cells, decidua, neurones such as Purkinje cells of the cerebellum, glandular epithelial cells and stromal cells of the prostate, cardiac myocytes and bronchial epithelial cells. Cytoplasmic staining was noted in Purkinje cells, glandular epithelium of prostate, exocrine pancreas and renal tubular epithelium. The 1801 antibody did not produce staining in any of these tissues. CONCLUSIONS: Our study demonstrates the presence of p53 in normal paraffin-embedded tissue with nuclear and/or cytoplasmic localization in some instances. In our view, DO7 appears to be better suited for such detection.

Antigens↗
PubMed2002

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas.

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing alphaVbeta3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and alphaVbeta3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0--60%) expressed LH39, while alphaVbeta3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5--90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.

Carcinoma, Non-Small-Cell Lung↗
PubMed2002

Expression of angiogenic factors and hypoxia inducible factors HIF 1, HIF 2 and CA IX in non-Hodgkin's lymphoma.

AIMS: Angiogenesis in solid tumour pathology is well established but less is known about its role in haematological malignancies. Our study investigated the immunohistochemical expression of a variety of angiogenic and hypoxic factors and microvessel densities on 110 cases of high- and low-grade non-Hodgkin's lymphomas and reactive lymphoid tissues. methods and results: Expression of vascular endothelial growth factor (VEGF) was present in 82 (96%) of the non-Hodgkin's cases and 35 (100%) of the reactive lymphoid tissue cases. Both hypoxia inducible factors 1 alpha and 2 alpha (HIF 1 alpha, 2 alpha) were weakly expressed in the majority of high- and low-grade lymphomas. Carbonic anhydrase IX (CA IX), a HIF-inducible membrane-bound enzyme, expression was not abundant with membranous staining being present in seven (8%) of the lymphoma cases and none of the reactive cases. Thymidine phosphorylase (TP) was distributed amongst macrophages and follicular dendritic cells but was not present in the neoplastic population. The vasculature was stained using CD34 which gave rise to a distinct vascular, predominantly paracortical network present in low-grade lymphomas and reactive lymphoid tissue but which was lost in high-grade lymphomas. CONCLUSION: Our results suggest that non-Hodgkin's lymphomas may be less angiogenic and hypoxically driven than most solid tumours, which has implications for possible future therapies.

Angiogenesis Inducing Agents↗
PubMed2001

Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival.

Hypoxia inducible factors HIF1alpha and HIF2alpha are important proteins involved in the regulation of the transcription of a variety of genes related to erythropoiesis, glycolysis and angiogenesis. Hypoxic stimulation results in rapid increase of the HIF1alpha and 2alpha protein levels, as a consequence of a redox-sensitive stabilization. The HIFalphas enter the nucleus, heterodimerize with the HIF1beta protein, and bind to DNA at the hypoxia response elements (HREs) of target genes. In this study we evaluated the immunohistochemical expression of these proteins in 108 tissue samples from non-small-cell lung cancer (NSCLC) and in normal lung tissues. Both proteins showed a mixed cytoplasmic/nuclear pattern of expression in cancer cells, tumoural vessels and tumour-infiltrating macrophages, as well as in areas of metaplasia, while normal lung components showed negative or very weak cytoplasmic staining. Positive HIF1alpha and HIF2alpha expression was noted in 68/108 (62%) and in 54/108 (50%) of cases respectively. Correlation analysis of HIF2alpha expression with HIF1alpha expression showed a significant association (P< 0.0001, r = 0.44). A strong association of the expression of both proteins with the angiogenic factors VEGF (P< 0.004), PD-ECGF (P< 0.003) and bFGF (P< 0.04) was noted. HIF1alpha correlated with the expression of bek-bFGF receptor expression (P = 0.01), while HIF2alpha was associated with intense VEGF/KDR-activated vascularization (P = 0.002). HIF2alpha protein was less frequently expressed in cases with a medium microvessel density (MVD); a high rate of expression was noted in cases with both low and high MVD (P = 0.006). Analysis of overall survival showed that HIF2alpha expression was related to poor outcome (P = 0.008), even in the group of patients with low MVD (P = 0.009). HIF1alpha expression was marginally associated with poor prognosis (P = 0.08). In multivariate analysis HIF2alpha expression was an independent prognostic indicator (P = 0.006, t-ratio 2.7). We conclude that HIF1alpha and HIF2alpha overexpression is a common event in NSCLC, which is related to the up-regulation of various angiogenic factors and with poor prognosis. Targeting the HIF pathway may prove of importance in the treatment of NSCLC.

Adenocarcinoma↗
PubMed2001

Prevalence of headache in an elderly population: attack frequency, disability, and use of medication.

OBJECTIVES: To assess the 1 year prevalence of tension-type headache (TTH), migraine headache (MH), and chronic daily headache (CDH), as well as of headache in general in a rural elderly population. METHODS: A door to door two phase survey was carried out on all elderly (>/=65 years) residents in three villages in central Italy. Participants completed a standardised headache questionnaire and underwent a clinical evaluation by a neurologist. Headache diagnosis was made according to the classification of the International Headache Society, with minor modifications for the classification of patients with MH with>/=15 attacks/month. RESULTS: Eight hundred and thirty three (72.6%) of the 1147 eligible persons completed the study protocol. One year prevalence rates were respectively 44.5% for TTH, 11.0% for MH, 2.2% for symptomatic headaches, and 0.7% for the remaining types of headache. The prevalence of headache in general was 51.0% because 62 residents had both TTH and MH attacks. Prevalence rates of patients with headache were higher in women than men (62.1% and 36.6% respectively) and decreased steadily with age for the 65-74, 75-84, and 85-96 age groups (56.7%, 45.2% and 26.1% respectively). Prevalence rates were 20.4% for patients with moderate to severe attacks, 18.0% for those with >/=1 attacks a month, and 4.4% for those with CDH. Of the 425 with headache 52 (12.2%) had not taken any drugs for their attacks in the previous year, 195 (45.9%) had taken them regularly, and 178 (41.9%) had taken them only when the headache pain interfered with activities that could not be postponed. Medication overuse was reported by 37.8% of patients with CDH with higher proportions for transformed migraine than for patients with chronic TTH (69.2% and 23.8% respectively, p=0.009) CONCLUSIONS: A consistent proportion of elderly people have primary headaches and consultation with a specialist is particularly recommended for patients with moderate or severe attacks, or with CDH.

Adult↗
PubMed2001

Relationship of the K-ras/c-mos expression patterns with angiogenesis in non-small cell lung carcinomas.

BACKGROUND: Neo-angiogenesis is an acquired capability vital for a tumor to grow and metastasize. Evidence has shown that the mitogen-activated protein (MAP) kinase pathway is involved in this process. Alterations of K-ras and c-mos, two pivotal components of this pathway, have been implicated in non-small cell lung carcinogenesis. In the present report, we examine, in a series of non-small cell lung carcinomas (NSCLCs), the status of K-ras and c-mos oncoproteins in correlation with the tumor neo-angiogenesis state and the major angiogenic factor, vascular endothelial growth factor (VEGF). MATERIALS AND METHODS: c-mos and p-ERK1/2 status was evaluated immunohistochemically in a total of 65 NSCLCs, whereas the presence of K-ras mutations was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) restriction fragment length polymorphism (RFLP) in available matched normal tumor material from 56 cases. Microvessel density (MVD) was estimated by immunodetection of CD3, endothelial marker, and VEGF expression was assessed by immunohistochemistry. All possible associations were examined by a series of statistical methods. RESULTS: Expression of oncogenic activated K-ras and c-mos overexpression was observed in 12 of 49 (25%) and in 16 of 61 (26%) informative cases, respectively. Only 1 of the 25 deregulated for K-ras or c-mos cases exhibited both alterations, suggesting a mutually exclusive relationship between activated K-ras and c-mos overexpression (p = 0.074) in a subset of NSCLCs. In these cases, the MAPK kinase kinase/MEK/ERK pathway was found to be activated. MVD and VEGF expression were 36.9 +/- 10.6 mv/mm2 and 73.1 +/- 20.0%, respectively. The most intriguing finding was that the [K-ras(No)/c-mos(P)] profile was significantly associated with low MVD levels compared to normal cases (p = 0.004); by contrast, no correlation was found between the other K-ras/c-mos patterns and MVD. Furthermore, the former group exhibited the lowest VEGF levels. CONCLUSIONS: The mutually exclusive relationship between mutated K-ras and c-mos overexpression in a subset of NSCLCs implies a common signal transduction pathway in lung carcinogenesis. The effect of this pathway on NSCLC neo-angiogenesis seems to depend upon the status of c-mos, which acts as a molecular "switch," possibly exerting a negative selective pressure on tumor progression.

Carcinoma, Non-Small-Cell Lung↗
PubMed2000

The diagnosis of low-grade peripheral B-cell neoplasms in bone marrow trephines.

The aim of this study was to establish how effective is the use of immunohistochemistry on formalin-fixed bone marrow in diagnosing low-grade B-cell neoplasms. We investigated a series of 41 consecutive patients with bone marrow involvement for whom no other diagnostic tissues were available. The sections were stained with the following antibodies: CD3, CD20, CD79a, CD5, CD10, CD23, anti-cyclin D1 and kappa and lambda light chains. Antigen retrieval was performed using either a microwave oven or a pressure cooker. Labelling was performed with an avidin-biotin-peroxidase labelling system. A final diagnosis was reached in 37 out of 41 cases (90%): B-chronic lymphocytic leukaemia (15 cases), follicular lymphoma (10 cases), mantle-cell lymphoma (eight cases) and lymphoplasmacytoid lymphoma/immunocytoma (four cases). In the remaining four cases, a generic diagnosis of low-grade B-cell neoplasm was made. The immunophenotyping of formalin-fixed marrow is a useful technique for diagnosing most of the low-grade B-cell neoplasms.

Antigens, CD↗
PubMed1999

Simultaneous phenotypically distinct but clonally identical mucosa-associated lymphoid tissue and follicular lymphoma in a patient with Sjögren's syndrome.

A 44-year-old woman with a 12-year history of Sjögren's syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.

Adult↗
PubMed1999

Angiogenesis in myelodysplastic syndromes.

It is now well established that solid tumour growth depends on angiogenesis. However, less is known about the generation of new vessels in haematological malignancies and, in particular, in preleukaemic-myelodysplastic syndromes (MDS). In this study, bone marrow microvessel density (MVD) was assessed by immunohistochemistry and compared in trephine biopsies from 14 controls, five infectious disease (ID), 82 MDS, 15 acute myeloid leukaemia (AML) and 14 myeloproliferative disorder (MPD) patients. Statistical analysis (P < 0.001) demonstrated that MDS MVD was higher than in controls and ID (21 +/- 9 vs 6 +/- 2 and 10 +/- 8 respectively) but lower than AML (30 +/- 12) and MPD (40 +/- 12). Among MDS-FAB subtypes, MVD was significantly higher in RAEB-t, CMML and fibrosis subsets compared to RA, RARS and RAEB subsets (P= 0.008). To further investigate angiogenesis machinery, the expression of vascular endothelial growth factor (VEGF) was evaluated by means of immunohistochemistry in control, MDS, AML and MPD biopsies. Even though VEGF mRNA expression was reported in the past in AML cell cultures and cell lines, in our samples VEGF expression was found to be particularly strong in most of the megakaryocytes but significantly less prominent in other cell populations including blasts. Since our findings suggest a correlation between angiogenesis and progression to leukaemia, additional work is now warranted to determine what regulates the generation of new vessels in MDS and leukaemia.

Antigens, CD34↗
PubMed1999

An unusual case of intrapulmonary granulocytic sarcoma presenting as interstitial pneumonitis following allogeneic bone marrow transplantation for acute myeloid leukaemia and responding to donor lymphocyte infusion.

We report a 45-year-old female with AML who underwent a T cell-depleted sibling allograft and relapsed a year later with extramedullary disease involving the lung parenchyma and presenting with the clinical and radiological features of interstitial pneumonitis. The patient was treated with donor lymphocyte infusion (DLI) resulting in complete resolution of the radiological signs. The unusual presentation and the management options are discussed.

Bone Marrow Transplantation↗
PubMed1998

Loss of FHIT function in lung cancer and preinvasive bronchial lesions.

We previously cloned and characterized the tumor suppressor gene FHIT (fragile histidine triad) at chromosome 3p14.2 and found that this gene is altered by deletions in human tumors, including lung cancer. To assess the frequency and specificity of inactivation and its relevance in a clinical setting, we have produced antibodies against the Fhit protein and studied its expression in a series of non-small cell lung cancers and normal bronchial mucosa and a spectrum of preinvasive lesions by immunohistochemistry. The data indicate that the loss of Fhit protein is the most frequent alteration in non-small cell lung cancer (73%) and precancerous lesions (93%), is significantly higher in the tumors of smokers (75%) than in those of nonsmokers (39%; P < 0.0005), and is an independent and more frequent event than p53 overexpression in tumors and precancerous lesions (73 versus 46%). The percentage of cases lacking Fhit expression was higher in the squamous type compared to adenocarcinoma (87 versus 57%; P < 0.00001), whereas other histotypes (large cell, mucoepidermal) showed an intermediate value (69%). Loss of Fhit expression in a very high percentage of primary lung carcinomas and precancerous lesions supports the notion that FHIT alterations play an important role in the growth control of bronchial cells. FHIT inactivation is particularly important in squamous cell carcinomas that are often associated with precursor dysplastic lesions. The overall high frequency and precocity of Fhit loss in lung carcinogenesis and the development of the presently described immunohistochemical approach suggest a potential use of this gene in the early detection of lung cancer and in chemopreventive studies as an intermediate biomarker.

Acid Anhydride Hydrolases↗
PubMed1998

Schnyder corneal crystalline dystrophy: description of a new family with evidence of abnormal lipid storage in skin fibroblasts.

Schnyder corneal crystalline dystrophy (SCCD) comprises corneal opacities often associated with precocious arcus senilis and genua valga. The metabolic defect seems to be related to abnormal lipid storage in the central part of the cornea, especially the anterior stroma, consisting mainly of nonesterified cholesterol. Plasma lipid levels are not always increased suggesting that the disease may be due to abnormal lipid metabolism limited to the cornea. We observed a family with typical SCCD, in 1 case associated with mental retardation and mild cerebellar hypoplasia. Results of serum lipid analysis of all patients were normal. Ultrastructural study of a skin biopsy specimen and fibroblast pellet showed membrane-bound spherical vacuoles containing lipid material. Cultured fibroblasts stained by filipin, a fluorescent probe that specifically binds unesterified cholesterol, showed abnormal cytoplasmic fluorescent material, suggesting abnormal cholesterol metabolism. The presence of neurological impairment, associated with SCCD in 1 of our cases, may be regarded as coincidental. Evidence of storage lipids in skin and cultured fibroblasts suggests that the disorder of intracellular cholesterol metabolism is not limited to the cornea and that skin biopsy may be a useful method to confirm the diagnosis.

Adult↗
PubMed1998

Co-expression of CD79a (JCB117) and CD3 by lymphoblastic lymphoma.

Acute lymphoblastic leukaemia/lymphoma is a malignant disorder derived from the clonal proliferation of lymphoid precursor cells. Whether the tumour cells are of B- or T-cell type is an important criterion for prognosis which has not been available previously to pathologists, due to the lack of a reliable early B-cell marker functioning on routinely processed material. This has changed with the production of monoclonal antibodies against the B-cell signalling molecule CD79a. CD79a is expressed on normal and neoplastic B cells from the early stages of B-cell maturation and has been considered to be B-cell-specific. Currently available antibodies against CD79a, in particular JCB117, allow the identification of B cells, and hence B lymphoblastic disease, in paraffin-embedded material. In this study, the expression of CD79a (JCB117) and CD3 has been investigated in 149 cases of T and 68 cases of B lymphoblastic leukaemia/lymphoma. For the first time, co-expression of CD79a (JCB117) and CD3 is reported in 10 per cent of cases of T lymphoblastic leukaemia/lymphoma. This finding raises questions about the co-expression of T- and B-cell markers in the development of lymphocytes, benign as well as malignant, and alerts pathologists to a potential problem in diagnosis.

Antigens, CD↗