Biomedical subjects

Guido Valente

Publications and source records attributed to Guido Valente.

12 recordsLinked to original sources

PubMed2006

Simultaneous diagnosis of CD3+ T-cell large granular lymphocyte leukaemia and true thymic hyperplasia.

CD3+ T-cell large granular lymphocyte (LGL) leukaemia is a mature T-cell neoplasm of cytotoxic T-lymphocytes. Neutropenia represents the most frequent peripheral blood cytopenia associated with CD3+ T-cell LGL leukaemia. A wide variety of diseases associated with LGL leukaemia have been reported, both autoimmune and neoplastic. We describe for the first time the association of true thymic hyperplasia with CD3+ T-cell line LGL leukaemia. The patient presented with severe symptomatic neutropenia. Complete and persistent haematological and molecular remission was induced with an association of low-dose methotrexate and cyclosporin A, followed by thymectomy.

Arthritis, Rheumatoid↗

PubMed2006

Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas.

The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies). The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.4%), mucinous adenocarcinoma (mainly made up of signet-ring cell patterns) in 15 (14.3%), and adenoid cystic carcinoma in 7 (6.7%). Microvessel density values (in vessels per square millimeter), VEGF, and Ki-67 were not dependent on histologic type but were rather correlated to the histologic grading in SCC. Clinical data were available for 92 (87.6%) of 105 patients, with minimum follow-up of 48 months. Most of the patients (81.5%) were at an advanced stage (T3-T4) at diagnosis. The values of all markers were correlated to tumor stage (P = .03). Multivariate analysis showed that both microvessel density and proliferative activity of the neoplastic cells were independent prognostic parameters (mortality hazard ratio, 1.33 and 1.60, respectively). Although VEGF expression was not correlated to prognosis on the whole series (P = .06), it was a powerful prognostic marker when the analysis was restricted to the group of SCCs (hazard ratio, 3.02; 90% confidence interval, 1.58-5.80). These results show that tumor neoangiogenesis, expressed by microvessel density, together with proliferative activity, is a pathologic marker with a strong prognostic impact in sinonasal carcinomas. Therefore, it may be a useful tool in this field so as to carry out therapeutic protocol planning, which may be further enhanced by the adoption of the more recent antiangiogenic molecules.

Adenocarcinoma↗

PubMed2006

cFLIP expression correlates with tumour progression and patient outcome in non-Hodgkin lymphomas of low grade of malignancy.

The present study investigated whether the expression of cellular Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (cFLIP) conveys prognostic information in non-Hodgkin lymphomas (NHLs). cFLIP expression was quantified by immunohistochemistry and immunofluorescence in biopsy specimens from 86 NHL patients for whom clinical information was available. NHL malignancy was graded as high/intermediate or low according to the World Health Organization Classification of Lymphoid Neoplasms. cFLIP was positive in 23 of 45 high-/intermediate-grade NHLs and in 25 of 41 low-grade NHLs. Negative expression of cFLIP was associated with the presence of apoptotic cells in the tumour mass, regardless of the histotype and of the malignancy grade. In NHLs positive for cFLIP, 11 of 23 (48%) high-/intermediate-grade cases and 18 of 25 (72%) low-grade cases showed a bad outcome. In NHLs negative for cFLIP, only four of 22 (18%) high-/intermediate-grade patients and 12 of 16 (75%) low-grade patients achieved complete remission. All these correlations were statistically significant. The correlation of cFLIP expression with clinical outcome was independent of therapy, whether or not it included anti-CD20 antibody (Rituximab). The present findings strongly indicate that cFLIP is a reliable predictor of tumour progression and clinical prognosis in NHLs of low grade of malignancy.

Aged↗

PubMed2006

Long pentraxin 3: a marker of inflammation in untreated psoriatic patients.

Psoriasis is a common cutaneous disorder characterized by abnormal epidermal differentiation, proliferation and inflammation mediated by dermal infiltrates, such as T cells, neutrophils, dendritic cells and macrophages. There are renewed interest in the role of components of the innate immune system. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6, and -1beta involved in pathogenic phenomena in psoriasis are known as inducers of the acute phase response. Among the large group of acute phase reactants, C-reactive protein (CRP) and fibrinogen are of special interest in psoriasis. The PTX-3, a long pentraxin sharing similarities with the classical short proteins. Thus, considering the numerous biological roles of inflammatory cytokines and their relationship with inflammatory markers, such as CRP and fibrinogen we have investigated the role of PTX3 in psoriasis. To this aim PTX3, TNF-alpha, IL-6 and IL-1beta in plasma and in monocytic cultures by enzyme linked immunosorbent assay (ELISA) in 44 patients including severe and mild psoriasis were measured. An increased production of PTX3, both in supernatant of purified monocytes and in plasma from patients with severe psoriasis, was found. The significant correlation, between cellular production and plasma levels of PTX3 in psoriasis was found as a sign of cellular activation by monocytes/macrophages that first infiltrate the psoriatic lesion. In severe psoriasis, a significant correlation between psoriasis area and severity index (PASI) score and TNF-alpha and IL-6 levels in both supernatant of monocytes and plasma was found. In contrast, no correlation was found for IL-1beta. By immunohistochemistry and immunofluorescence, a strong PTX3 staining in fibroblasts, endothelial cells and monocytes/macrophages in severe psoriatic lesional skin was detected. Finally, a positive correlation between PTX3 and disease activity of psoriasis was observed as PASI score was elevated. These findings suggest that PTX3 could be used as a further marker of disease activity of psoriasis.

Adult↗

PubMed2006

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes.

Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens. Immunohistochemistry with specific anti-KIT and anti-SCF antibodies was performed on paraffin-embedded tissue sections in order to localize the relative protein expression in epithelial compartments. Approximately 10% of patients expressed KIT in their adenoma or primary tumor. The majority of KIT-positive carcinomas co-expressed SCF. Real-time RT-PCR showed expression of c-kit and SCF transcripts in all cDNA specimens examined. A significant association between the co-expression of KIT/SCF and a worse clinical outcome was found. In conclusion, KIT expression was observed in a proportion of premalignant and malignant colonic lesions, while it was virtually absent in normal colon mucosa. Moreover, the majority of KIT-positive carcinomas co-expressed SCF, suggesting the possibility of aberrant signaling by an autocrine loop, as confirmed by the negative prognostic value of this association. Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy.

Adult↗

PubMed2005

Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy.

AIM: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC). METHODS: Samples from 317 (184 males, 133 females, mean age 69+/-3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five (294 males, 261 females, mean age 57.3+/-4.1 years) patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic "gold standard". An enzyme immunosorbent assay was used to detect serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized to search for anti-CagA protein (IgG). RESULTS: Two hundred and sixty-one of three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the 317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555 (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference between the frequency of H pylori in intestinal type carcinoma (76.2%) and diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and 72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I, 8.3% type II and 51.9% type III(type III vs others, P = 0.4). CONCLUSION: This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor.

Adenocarcinoma↗

PubMed2005

Hemangiopericytoma of the infratemporal fossa: progression toward malignancy in a 30-year history.

Hemangiopericytoma is a rare vascular tumor first described by Stout and Murray in 1942 and characterized by a proliferation of Zimmermann's pericytes, smooth muscle cells arranged around blood vessels. This tumor presents as a slowly enlarging painless mass. Diagnosis with certainty is often a difficult one because of the close likeness with other spindle cell tumors; it requires the help of immunohistochemical techniques and sometimes ultrastructural techniques. Only 15% of hemangiopericytomas are localized in the cervicofacial region; in particular, occurrence in the infratemporal fossa is an exceptional occurrence. In this article, we report an unusual case of recidivate hemangiopericytoma of the infratemporal fossa that has progressively assumed features of malignancy over 30 years. The hemangiopericytoma relapse potentiality is elevated, even when the histologic characteristics of the tumor indicate a low aggressivity, and therefore every hemangiopericytoma must be considered to have malignant potential. In conclusion, the unpredictable behavior of hemangiopericytoma requires a radical primary treatment to avoid the risk of relapses that always are frequent and aggressive.

Aged↗

PubMed2004

Evidence of p53 immunohistochemical overexpression in ethmoidal mucosa of woodworkers.

A high risk of neoplastic transformation of nasal and paranasal sinuses mucosa is related to the occupational exposure to wood dust, however no conclusive data have been reported up to now about morphological precursors of these tumors, mechanisms of carcinogenesis and role of p53 gene. Immunohistochemical overexpression of protein p53 (DO7 clone) by epithelial cells of ethmoidal mucosa was investigated on 60 woodworkers occupationally exposed for a minimum of 10 years, on 50 functional and/or esthetic nasal surgery patients (control group) and on 15 cases of intestinal-type adenocarcinoma, 10 of these involving subjects who had a longtime exposure to wood dust. In almost all the woodworkers (92%) the normal ciliated epithelium showed tracts of squamous metaplasia. The mean percentage of p53-positive cells in woodworkers and in controls was 28.6 and 7.97%, respectively, in metaplastic epithelium (P<0.001), 11.7 and 2.08% in ciliated epithelium (P<0.001), 12.46 and 1.03% (P<0.001) in the sero-mucous glands of the nasal stroma. Both in tracts of metaplastic epithelium and in those of ciliated epithelium, positive cells were distributed in basal and suprabasal layers. A high number of p53-positive cells was also observed in the normal ciliated epithelium close to the neoplastic cells, of intestinal-type adenocarcinomas affecting subjects with longtime exposure to wood dust. Moreover, a higher number of p53 positive neoplastic cells was showed by the cases occurring in occupationally exposed patients than by the others. The following conclusions can be drawn: (1) in the ethmoidal mucosa, a region at high risk of carcinogenesis in subjects exposed to wood dust, epithelial cells overexpress p53 protein, and this may be linked to the presence of p53 gene mutations; malignant transformation, as at other head and neck sites, may thus occur through this pathway; (2) the presence of p53 overexpression in sero-mucous glands is in keeping with the histogenesis of some tumors from these structures; (3) since tumors of nose and paranasal sinuses, mainly adenocarcinoma, are recognized as occupational neoplasias, immunohistochemical evaluation of p53, perhaps combined with molecular methods, could be the first step to detect subjects at high risk of carcinogenesis among woodworkers.

Adenocarcinoma↗

PubMed2004

Histological score for cells with irregular nuclear contours for the diagnosis of reflux esophagitis in children.

Histological criteria for the diagnosis of reflux esophagitis include basal zone hyperplasia, stromal papillae elongation, and inflammatory infiltrate. However, endoscopic esophageal biopsy specimens may include little or no lamina propria. Intraepithelial T lymphocytes, seen in hematoxylin and eosin-stained sections as cells with irregular nuclear contours (CINC), may have a higher density in children with esophagitis. We evaluated the diagnostic accuracy of a numerical score built up by grading the "classical" parameters and its correlation with CINC density in grasp biopsy specimens obtained from children undergoing esophagogastroduodenoscopy with and without esophagitis. We analyzed esophageal biopsy specimens from 349 children (median age, 5 years) subdivided in 4 groups according to the previous routine histology report: group 1, 144 children with esophagitis; group 2, 65 controls; group 3, 51 children with dubious esophagitis; and group 4, 75 children with esophagitis on endoscopy but a normal histology report. A numerical value was assigned to each parameter; the sum of these values represented the histological score. We also evaluated intraepithelial CINC density (ie, number of CINC per high-power field). We separately analyzed histological sections with and without lamina propria. For both total score and for CINC density, we calculated a cutoff using a receiver operating characteristic curve. Cutoffs of 6 for score and of 4 for CINC density provided the best sensitivity and specificity. Sensitivity of the histological score was better in biopsy specimens containing lamina propria (94%) than in those without lamina propria (4%). Sensitivity of CINC density was satisfactory in both specimens with (78%) and without (75%) lamina propria. Specificity was satisfactory for both parameters. In conclusion, when lamina propria was present in sections of endoscopic esophageal biopsy specimens, histological score provided a better diagnostic accuracy for the diagnosis of esophagitis. However, when no lamina propria was present, as was the case in 67% of our children, CINC density had better sensitivity. In addition, this latter parameter showed esophageal mucosa damage in 34% of previously dubious cases or cases with esophagitis at endoscopy but a previous routine histology report of normal mucosa.

Adolescent↗

PubMed2002

Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells.

This is the first description of an extensive immunohistochemical analysis of interferon (IFN)-inducible gene IFI16 expression in normal tissues. Immunohistochemical detection of IFI16 in paraffin-embedded tissues is achieved by using a polyclonal antibody raised against its C-terminal fragment that recognizes its three closely migrating isoforms in Western blotting. The results clearly indicate that IFI16 expression is not restricted to the hematopoietic compartment. In normal adult human tissues, it is prominent in stratified squamous epithelia and particularly intense in parabasal cells in the proliferating compartments, but it gradually decreases in the more differentiated suprabasal layers. Understanding of IFI16 expression in vivo is essential for interpretation of the results obtained from in vitro studies and elucidation of its physiologic role. The constitutive expression and wider distribution of IFI16 in normal human tissues, not restricted to the hematopoietic compartment, strongly support the possibility of an important role in cell differentiation that can be further modulated by other stimuli, such as IFN.

Blotting, Western↗

PubMed2002

[Nasopharyngeal tuberculosis].

Nasopharyngeal tuberculosis is a rare condition and, sometimes, associated with a cervical lymphadenopathy. The authors report a case of an isolated nasopharyngeal tuberculosis in a 69-year-old female with otological symptoms. The case is remarkable because of its coming in a non-endemic zone for the tuberculosis, and because of its probable persistence by many years.

Aged↗

PubMedDate not supplied

Human herpesvirus type 8-associated primary lymphomatous effusion in an elderly HIV-negative patient: clinical and molecular characterization.

Primary lymphomatous effusions are defined as lymphomas presenting in the serous body cavities in the absence of clinically identifiable tumor masses. Recently, a peculiar type of primary lymphomatous effusion associated with tumor clone infection by human herpesvirus type 8 (HHV-8) and preferentially arising in HIV-positive patients has been described and termed as primary effusion lymphoma (PEL). This report describes a case of PEL which has developed in a HIV-negative, 92-year-old man with longstanding Mediterranean Kaposi's sarcoma, a disease also associated with HHV-8 infection. The patient presented with pleural and ascitic effusions in the absence of solid masses within the lungs, mediastinum, thoracic wall or abdominal cavity. The effusions consisted of malignant lymphocytes with morphologic features bridging immunoblastic and anaplastic cells. Immunophenotypic studies revealed that the lymphoma population expressed an antigenic profile consistent with PEL, i.e. the absence of common B- and T-cell markers (non-B, non-T phenotype) coupled to CD138 positivity. Molecular analysis demonstrated infection of the tumor clone by HHV-8 as well as monoclonally rearranged immunoglobulin genes, consistent with a B-cell histogenesis of the lymphoma. In addition, this PEL case harbored PAX-5 gene mutations, which have been recently demonstrated as a key feature of the proto-oncogene hypermutation process involved in the pathogenesis of some lymphoma types. Following two courses of etoposide and prednisone, a partial remission was achieved. The patient died of liver failure 3 months after the diagnosis of PEL. Overall, this case report illustrates the need for an integrated diagnostic approach based on clinical features, morphology, immunophenotype, and molecular genetics to primary lymphomatous effusions.

Aged↗