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G Valente

Publications and source records attributed to G Valente.

At least 55 records · Page 3Linked to original sources
PubMed1996

Human herpesvirus 6 and Epstein-Barr virus in Hodgkin's disease: a controlled study by polymerase chain reaction and in situ hybridization.

Human herpesvirus-6 (HHV-6), a T-lymphotropic double-stranded DNA virus highly endemic in human populations, has been suggested to play a possible role in the development of lymphoid neoplasms, especially Hodgkin's disease. To investigate this point, we evaluated the presence and distribution of HHV-6 DNA by Southern blot, nested polymerase chain reaction, and in situ hybridization in a series of lymphoproliferative disorders including 73 Hodgkin's disease cases, 15 non-Hodgkin lymphomas, and 19 reactive lymph nodes. A high prevalence of HHV-6 infection was observed within the Hodgkin's disease category by polymerase chain reaction (38 of 52, 73%) and in situ hybridization (47 of 57, 82.4%); however, a similar prevalence was found in non-Hodgkin's lymphomas (10 of 15, 66.6%) and reactive lymph nodes (13 of 19, 68.4%). In no case did Southern blot detect viral DNA, suggesting that the neoplastic tissue contained a low number of HHV-6 copies. In situ hybridization showed that the HHV-6 positivity was restricted to lymphocytes, whereas Hodgkin and Reed-Sternberg cells were consistently negative. Immunohistochemical staining with specific monoclonal antibodies against viral structural proteins was also negative, indicating the absence of a productive infection. No relationship was observed between HHV-6 positivity and histological type, clinical parameters, and outcome of the disease. In the same series, a high proportion of cases (39 of 52, 75%) showed the presence of the Epstein-Barr virus (EBV) genome by polymerase chain reaction; In situ hybridization for Epstein-Barr-virus-encoded small RNA and immunohistochemical detection of latent membrane protein-1 gave similar results (73.6% of positive cases with both methods). In 54.9% of the cases, both sequences of HHV-6 and Epstein-Barr virus DNA were found, suggesting that a synergism of the two viruses may occur. However, the lack of detectable HHV-6 DNA in Reed-Sternberg and Hodgkin's cells seems to argue against such an interpretation. Based on these results, HHV-6 does not appear to play a specific role in the pathogenesis of Hodgkin's disease.

Blotting, Southern↗
PubMed1996

[Laryngeal cancer and angiogenesis].

Angiogenesis is required for the growth of solid tumors which, in avascular condition, are limited to 2-3 mm3 volume. The switch to the angiogenic phenotype allows new vessels to converge upon the tumor, growth to proceed at an exponential rate and metastasis diffusion. The evaluation of tumoral angiogenesis has been proposed to be an independent prognostic marker of behaviour of some solid tumors: it has been demonstrated that, in some types of carcinoma (breast, prostate, lung, etc...), an intense vascular proliferation correlates with the aggressiveness of the disease. However in malignant melanomas and colorectal carcinomas, there are conflicting results on the correlation between angiogenesis and the progression of the cancer. There are also conflicting data on the role of microvessels count (MC) in the management of head and neck cancer. Despite a large number of studies, at the present, there are not biological or molecular markers available to predict consistently the outcome of the patients with laryngeal squamous cell carcinoma (LSCC). In fact the prognosis of this tumor has been mainly based, up to now, on a number of clinico-pathological parameters, especially localization, tumor extent and nodal involvement. The aim of this study has been to compare MC inside LSCC with disease free survival, grading, pT, pN and pathological stage. We investigated the relevance of the number of microvessels in the peritumoral stroma of 68 LSCC (only Caucasian males, age 35-70 years), classified according to UICC/1987 randomly selected (33 classified in clinical stage I e II and 35 in clinical stage III-IV). All patients have been surgically treated and pN + cases have been also submitted to radiotherapy. The follow-up was 60-84 months. The vascular density was assessed according to Horak et Al. with an immunohistochemical method using JC70 monoclonal antibody (CD31; Dako, Astrup, Denmark). Univariate analysis showed that MC, pT, pN, Pathological Stage and grading were correlated with the disease-free survival. A MC < 120/mm2 was predictive for a high survival index; in contrast a MC > 150 mm2 were associated with relapse. Furthermore, multivariate analysis demonstrated that MC was the only independent predictor for the disease free survival. Our findings demonstrate that in LSCC, MC is the first measurable biological parameter which is significant for evaluating the disease free-survival. Therefore, MC in LSCC is crucial in the prognosis and in the choice of a more aggressive management of the disease, including the possible treatment with antiangiogenic compound.

Adult↗
PubMed1995

Minute and small early gastric cancers in a Western population: a clinicopathologic study.

Early endoscopic diagnosis improves the prognosis of patients with gastric cancer, as shown by the finding that 5-year survival rates exceeding 90% are observed in Japanese patients with early gastric cancer. It has been hypothesized that tumor size may have prognostic significance; therefore, a distinction between minute, small, and large early gastric cancers has been proposed. The aim of this study was to determine the prevalence of minute and small early gastric cancers in Western countries and to compare their clinicopathologic features with those of large early gastric cancers. Of 465 Italian patients with gastric cancer who were studied, 20.5% had an early gastric cancer, and 34.7% of these were minute or small. Tumor size is correlated with intramural spreading and metastasis to perigastric lymph nodes. Nodal involvement occurs more frequently in the diffuse than in the intestinal type of early gastric cancer. Long-term survival rate is not correlated with tumor size, intramural spreading, or nodal metastasis. The minute and small early gastric cancers of Italian patients are indistinguishable from those occurring in Japanese patients. These lesions are more common than previously thought and should be carefully searched for by endoscopists. The correlation of tumor size with intramural invasion and perigastric lymph node metastasis suggests that minute and small early gastric cancers are precursors of large early gastric cancers. Although the distinction between minute, small, and large early gastric cancers is of low prognostic value, the distinction might be useful for selecting different therapeutic approaches.

Female↗
PubMed1995

Is transposed skin transformed in major head and neck mucosal reconstruction?

We used histological and histochemical methods to investigate the possible changes with time in skin transposed into the oropharynx and oral cavity of patients whose surgical wounds were reconstructed with the classic pectoralis major flap. We found histological evidence that skin morphology was maintained (keratinization with reduced, but the desquamating layer, hair follicles, sweat and sebaceous glands were identifiable), and noted an intense inflammatory reaction in the dermis. Histochemical studies confirmed the progressive flattening of the basal interdigitations between the epithelium and dermis, and the gradual reconstruction of the basement membrane. Although skin-mucosa continuity developed fairly quickly without scar reactions, the two epithelia maintained their original patterns of keratin production, i.e., their textural peculiarities. We propose an original method for the transposition of muscular flaps implanted with autologous culture of keratinocytes, an approach developed in an attempt to ensure more satisfactory rehabilitation of the removed mucosal structures.

Carcinoma↗
PubMed1995

Prognostic factors for head and neck tumor recurrence.

The introduction of new treatment methods has stimulated the identification of further prognostic factors capable of defining the clinical and biological characteristics of the tumor type in question and improving treatment programming. The aim of this study was to identify which characteristics of the host and tumor are of prognostic value in relation to the onset of locoregional tumor recurrence. A total of 396 patients were studied. The tumor site distribution can be summarized as follows: 267 laryngohypopharyngeal, 74 oropharyngeal, 55 oral cavity. Variables regarding patient, tumor and histology were evaluated for the purpose of analysis. Multivariate analysis of these prognostic factors was performed using PLR software by BMDP. Mean tumor recurrence time was 19 months. Seventeen of the 29 variables analysed did not influence the probability of tumor recurrence. Two variables reduced the risk of tumor recurrence: age > 61 years and abundant and prevalently lymphocytic intra-and peritumoral infiltrate. The study of tumor recurrence onset mechanisms is justified by its impact on the evolution of disease. The use of multivariate analysis in this study showed that some clinical and pathological characteristics of squamous cell carcinoma of the head and neck have a statistically significant impact on tumor recurrence.

Adult↗
PubMed1995

Biological heterogeneity of diffuse mixed small and large cell non-Hodgkin's lymphomas assessed by DNA flow cytometry and Ki67.

The cell proliferative activity of the clinico-pathologically heterogeneous non-Hodgkin's lymphomas (NHL) included in the intermediate grade F category of the Working Formulation (WF) was investigated. S-phase fraction with flow cytometry on cell suspensions, and Ki67 on frozen tissue sections were performed in 42 F NHL. An avidin-biotin immunocomplex method was used and 1000 cells from 10 representative fields were counted. DNA content, S-phase and Ki67 were also detected in 194 NHL covering the whole spectrum of the WF. DNA content anomalies were found in 52 of 194 NHL. Their incidence, like that of S-phase fraction and Ki67 positive cells, progressively increased from low- to high-grade. A linear correlation was found between Ki67 and S-phase (r = .59). Using the median value of proliferating cells obtained with both procedures as a cut off, two very different groups of lymphomas could be distinguished within a series of 42 F-intermediate NHL: with low and high proliferative cell activity (p < .0001) that were termed F(low) and F(high), respectively. A intermediate group was placed between them. It differed significantly from the others if Ki67 was used but only from the F(high) group if the S-phase fraction analysis was applied. No significant differences were seen when comparing F(low) with the single categories of low-grade NHL and F(high) with H high-grade NHL; no significant differences were found between F(high) and G, and between G and H categories. The existence of distinct groups of NHL in the F category, as defined by biological parameters assessing the cell proliferative activity, indicates that this category includes biologically heterogeneous lymphoma subtypes with different grades of aggressiveness. The results also indicate that the G intermediate category displays proliferation indices similar to those of H high grade category.

Aneuploidy↗
PubMed1995

Primary gastric lymphomas (MALTomas): a nuclear image analysis comparison with lymph node monocytoid B-cells and marginal zones of spleen and Peyer's patches.

Centrocyte-like cells of marginal zones of follicles of gastrointestinal lymphoid tissue, which have their analogous in marginal zone of splenic white pulp and in lymph node monocytoid B-lymphocytes, are thought to be the normal counterpart of lymphomas of MALT (MALTomas). However, the cell population of MALTomas is often polymorphic and also contains cells morphologically different from centrocytes. Since conventional morphologic analysis may not be accurate enough and the phenotype may change in different stages of B-cell lineage, the marginal zone of Peyer's patches (PMZ) and splenic white pulp (SMZ), the lymph node monocytoid B-lymphocytes (ML), 3 nodal monocytoid B-cell lymphomas (L) and 16 gastric MALTomas (M) were studied by means of automated nuclear image analysis for area, irregularity, and chromatin texture assessment. Immunophenotyping on paraffin sections and polymerase chain reaction (PCR) for detecting monoclonality and t(14-18) chromosome breakpoints at DNA levels, on paraffin section extractions, were also done. In 14 MALTomas, clonal Ig heavy chain rearrangement was detected and in none of these were found t(14-18) chromosome breakpoints. The nuclei of the control group (PMZ, SMZ and ML) showed the same morphologic characteristics, ie. size, irregularity, chromatin texture. MALTomas and nodal lymphomas were distributed into 3 clusters: (1) with larger nuclei, light chromatin (euchromatin-richer) (5 MALTomas, 2 nodal lymphomas together with the control group); (2) nuclei with the same area size, but darker (eterochromatin-richer) (6 MALTomas and 1 nodal lymphoma); (3) with smaller and darker nuclei (5 MALTomas). Chromatin textural differences were maintained in the same nuclear size class in the 3 clusters. Only a few MALTomas had nuclear features not significantly different from controls, inter-case and intra-case variability being evident.

B-Lymphocytes↗
PubMed1995

[Prognostic factors in the radio-surgical treatment of laryngeal carcinoma].

We examined a homogeneous group of 116 patients with laryngeal and hypopharyngeal carcinomas, treated with surgery followed by radiotherapy according to the conventional procedure. The tumors occurred in the larynx in 88 cases (75.86%) and in the hypopharynx in 28 (24.14%); correlations between overall survival and disease-free survival on the one hand, and clinical and histological parameters on the other hand were established with a multivariate analysis using the Cox method. After 5 years 75.86% of the patients were alive. This variable was negatively influenced by pN (pN0 89.8%, pN1 76.2%, pN2 69%); pT (pT3 82.5%, pT4 62.5%), by vascular embolization (90% of patients alive with no vascular embolization versus 69.7% with vascular embolization), by the grade of peritumoral inflammation (64.3% of patients alive with slight peritumoral inflammation, 69.2% with medium-grade inflammation and 87.3% with strong inflammation), and finally by a great number of plasma cells and few granulocytes; 78.44% of these patients remained disease-free. This variable was negatively affected by pN (pN0 91.8%, pN1 76.2%, pN2 60%), patients' age and extracapsular spread (85.5% of disease-free patients with no extracapsular spread, vs. 51.55% with extracapsular spread); and positively influenced by basal cell differentiation (95% of disease-free patients versus 71.8%). Overall and disease-free survival rates which differed at the beginning, coincided after two years because of local recurrences. On the basis of these results we conclude that the correct assessment of morphologic variables should be considered as a useful tool for treatment planning.

Adult↗
PubMed1994

Immunohistochemical evaluation of P-glycoprotein in human malignancies by monoclonal antibody MC57.

P-glycoprotein expression was analyzed on 137 formalin-fixed, paraffin-embedded human tumours by monoclonal antibody (MAb) MC57. This MAb recognizes an extracellular human specific P-glycoprotein epitope and defines their multidrug resistance (MDR) phenotype by its binding on cells. Immunohistochemistry indicated that this MAb reacted in human cells and tissues in the same pattern as that found with other MAbs to P-glycoprotein. However, the present extensive study demonstrated that MAb MC57 is a highly specific reagent for the evaluation of an extracellular P-glycoprotein epitope preserved after fixation procedures and that this MAb is available to assess P-glycoprotein expression in routinely processed human tumour specimens.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Evidence for a glycidic-lipidic matrix in human neuromelanin, potentially responsible for the enhanced iron sequestering ability of substantia nigra.

The high-resolution solid-state 13C-NMR spectrum of a neuromelanin specimen (from patients dying from nonneurological diseases) is compared with that obtained from enzymatically prepared dopamine-melanin. The main differences between the two spectra suggest the occurrence in neuromelanin of a glycidic/lipidic matrix tightly associated with the melanin macromolecule. Atomic emission spectroscopy revealed high iron content (1.5%) in the neuromelanin specimen, in full agreement with previous reports. These observations support the view that neuromelanin acts as a strong chelating (and insolubilizing) system for iron ions and further suggest that the attack to this compact composite substrate may be an important step to allow the release of iron ions responsible for the increased lipid peroxidation reported in the pathogenesis of Parkinson's disease.

Carbon Isotopes↗
PubMed1994

Epstein-Barr virus detection by in situ hybridization in fine-needle aspiration biopsies.

Metastasis to neck lymph nodes is often the presenting symptom of occult head and neck tumors, including undifferentiated nasopharyngeal carcinoma (UNPC). The diagnosis of the primary site of the tumor by conventional cytological analysis of tissue obtained by fine-needle aspiration (FNA) may be difficult. As Epstein-Barr virus (EBV) infection is consistently associated with UNPC, we evaluated the diagnostic significance of EBV detection using a nonradioisotopic in situ hybridization assay. The data obtained by FNA from metastatic head and neck tumors was correlated with the histology of the corresponding surgical specimens. In a series of 25 FNA specimens of cervical lymph node metastases of tumors of unknown origin, EBV was found expressed in all seven metastases of UNPC but in none of 18 metastases of tumors of different types. Therefore, detection of EBV in cervical metastatic adenopathy may be successfully used to identify the presence of occult UNPC.

Adult↗
PubMed1994

Infection by Epstein-Barr virus in Hodgkin's disease is not restricted to the Reed-Sternberg cells.

The presence of Epstein-Barr virus (EBV) DNA was analysed by a non-radioisotopic in situ hybridization procedure within eight Hodgkin's disease tissues. Seven specimens contained EBV DNA, that was found not only within the Reed-Sternberg tumour cells, but also, to a varying degree, within the surrounding lymphocytes. The staining was more diffuse in the nodular sclerosis and interfollicular types, whereas it involved only a minority of lymphocytes in cases with mixed cellularity. Appropriate controls established the specificity of these findings. The widespread expression of EBV DNA within Hodgkin's disease tissue heavily underscores the involvement of EBV in the pathogenesis of this illness.

DNA, Viral↗
PubMed1994

B-cell chronic lymphocytic leukaemia stage 0. An immunophenotypic study of 66 cases and comparison with B small cell lymphomas.

The cells of 66 B-CLL stage 0 patients were analyzed using a large panel of monoclonal antibodies in order to better define the immunophenotype of B-CLL. The data were compared with the immunophenotypes of lymph node cells from 51 patients with diffuse B small cell lymphoma or leukaemia with lymph node enlargement. The most frequent immunophenotype of B-CLL stage 0 was SIgM(D)+ EmR+ CD5+ CD9+ CD21+ CD23+ CD35- CD38-. Among the lymphomas, EmR-positive and EmR-negative cases were identified. The vast majority of the EmR-positive cases usually showed the leukaemic pattern, immunophenotype and lymph node histology of B-CLL. The EmR-negative cases usually had immunophenotypes quite different from those of B-CLL and the histology of indented cell lymphoma (centrocytic or intermediate) or features of lymphoplasmacytoid/cytic lymphoma. More than 20% of EmR-positive cells proved to be the most important marker to distinguish B-CLL from other lymphocytic lymphomas. Indeed this was a sign of better prognosis. Lymphoplasmacytoid/cytic lymphomas were EmR-positive with the immunophenotype of B-CLL or EmR-negative with a definitely different immunological profile. This suggests two morphologically similar but biologically different subgroups of these diseases.

Antigens, CD↗
PubMed1994

MIB-1, Ki67, and PCNA scores and DNA flow cytometry in intermediate grade malignant lymphomas.

AIMS: To verify the correlation between MIB-1, Ki67, and proliferating cell nuclear antigen (PCNA-PC10) scores and S-phase fraction in intermediate grade non-Hodgkin's lymphomas (Working Formulation F); and their reliability in differently processed tissues. METHODS: Forty one non-Hodgkin's lymphomas were classified as (F) intermediate grade malignant lymphomas according to the Working Formulation; mitotic counts and percentage of large cells were assessed for each case. Sections from formalin fixed, paraffin wax embedded tissues were stained with anti MIB-1 monoclonal antibody, after microwave oven processing, and anti-PCNA (PC10) monoclonal antibody using an avidin-biotin immunoperoxidase (ABC) method. One thousand cells from 10 representative fields were scored. Frozen sections from surgical specimens were stained with Ki67 monoclonal antibody using the ABC method; the fraction of Ki67 positive cells was calculated scoring 1000 cells. Flow cytometry analysis (FCM) was performed on cell suspensions from fresh tissues. Correlations between data were estimated using linear regression. RESULTS: A linear correlation was found between MIB-1 and Ki67 scores (r = 0.92; p < 0.00001); between MIB-1 and PCNA scores (r = 0.79; p < 0.00001); and between MIB-1 score and S-phase fraction (r = 0.51; p = 0.0006). A linear correlation was also found between Ki67 and PCNA scores (r = 0.85; p < 0.00001); between Ki67 score and S-phase fraction (r = 0.6; p = 0.0002); and between PCNA score and S-phase fraction (r = 0.74; p < 0.00001). A correlation was found between mitotic counts and MIB-1 (r = 0.56; p = 0.0001), PCNA (r = 0.51; p = 0.0007), or Ki67 scores (r = 0.47; p = 0.002); between the percentage of large cells and MIB-1 (r = 0.49; p = 0.0009), PCNA (r = 0.6; p = 0.00003), and Ki67 scores (r = 0.53; p = 0.0003) and S-phase fraction (r = 0.55; p = 0.0002). CONCLUSION: MIB-1, Ki67, and PCNA (PC10) scores and S-phase fraction are highly correlated and equally well represent the proliferative activity of intermediate grade non-Hodgkin's lymphomas in differently processed material. MIB-1 and PCNA stains can be applied even on small biopsy specimens. MIB-1 produces homogenous staining without background; it also strongly stains mitotic figures. It can be performed on routinely processed tissues, permitting the simultaneous evaluation of the morphology and tumour cell kinetics. The wide standard deviations of the proliferative indices found for intermediate grade NHL suggest that this category probably includes various degrees of malignancy.

Antibodies, Monoclonal↗
PubMed1994

Can Ki67 immunostaining predict response to radiotherapy in oral squamous cell carcinoma?

AIMS: To determine whether immunohistochemical evaluation of the abatement of proliferating cells after a first course of radiotherapy could predict the final response to treatment in oral squamous cell carcinoma (SCC). METHODS: Frozen sections from 31 cases of histologically confirmed oral SCC were stained with the monoclonal antibody Ki67 at diagnosis and after 10 Gy of radiotherapy. The percentage difference of Ki67 positive cells among the biopsy specimens taken at the beginning and after 10 Gy was correlated with the clinical response obtained at the end of the treatment and its significance determined. RESULTS: The percentage of Ki67 positive cells at diagnosis had no significant correlation with the final therapeutic result of radiotherapy. By contrast, the 32% difference of proliferating cells after 10 Gy of radiotherapy significantly differentiated responders from non-responders (p < 0.05). Furthermore, the abatement of the growth fraction after 10 Gy of radiotherapy was significantly correlated with the complete response (p < 0.01). CONCLUSIONS: These data show that the immunohistochemical evaluation of the abatement of Ki67 positive cells after 10 Gy of radiotherapy provides an independent variable of responsiveness to radiotherapy, allowing a reliable prediction of the final therapeutic result to be made.

Antigens, Neoplasm↗