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M Boiocchi

Publications and source records attributed to M Boiocchi.

At least 127 records · Page 7Linked to original sources

Can a specifically-aimed pathologic classification overcome the difficulties in defining HIV-associated lymphomas?

High grade B-cell systemic lymphomas in HIV-infected patients exhibit pleomorphic features as well as some overlap between established histologic subtypes thus highlighting the difficulties in defining them precisely by making use of the classifications for non-Hodgkin's lymphomas (NHL) proposed before the AIDS epidemic. A series of HIV-associated systemic lymphomas including 114 NHL and 25 Hodgkin's disease (HD) cases were morphologically and immunopheno-genotypically investigated at the Centro di Riferimento Oncologico, Aviano, Italy during a period of nine years. The International Working Formulation (WF) for NHL, the updated Kiel Classification and, later, morphologic variants of high grade B-cell NHL have been adopted in order to obtain a more detailed and specific histopathologic description of HIV-associated lymphomas. As a consequence of morphologic data, and considering also pathogenetic aspects as derived from literature, we have attempted a pathological categorization of HIV-associated systemic lymphomas based on the recognition of two main groups: the "blastic" cell group and the "anaplastic" one, both including specific cytomorphologic subtypes with, possibly, aggressive HD subtypes within one of them. This categorization uses the WF, the updated Kiel system, and the morphologic variants of high-grade lymphomas, and provides a provisional category for cases with intermediate morphologic features. Thus other histologic subtypes, such as small noncleaved cell (Burkitt) and immunoblastic lymphomas, can be defined in a more accurate way. The clear-cut placement of "anaplastic" cell lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas and possibly a proportion of HD cases, emphasizes the need for their diagnostic differentiation from polymorphic "blastic"' cell lymphomas, immunoblastic ones in particular.

Humans↗

Local cytokine expression in the progression toward B cell malignancy in Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) has been indicated as an ideal human model to investigate B cell lymphomagenesis. Our aim was to investigate similarities or differences in cytokine expression in both prelymphomatous and frank B cell lymphomatous SS lesions, as well as in SS related lesions versus SS unrelated malignant B cell non-Hodgkin's lymphomas. METHODS: The mRNA expression of interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-6, IL-6R, IL-9, IL-10, IL-12, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) was analyzed by a sensitive reverse transcriptase polymerase chain reaction technique in 10 SS tissue samples from 10 consecutive patients [7 nonmalignant parotid myoepithelial sialadenitis (MESA) lesions with evidence of B cell clonal expansion, and 3 B cell non-Hodgkin's lymphomas] as well as a series of 11 SS unrelated B cell non-Hodgkin's lymphomas. RESULTS: IL-1, IL-2, IL-3, IL-6, IL-6R, IL-10, IL-12, IFN-gamma, TNF-alpha, and TGF-beta mRNA was expressed in all or in the vast majority of the samples analyzed. IL-4 mRNA was detected in 2/3 SS related and in 3/11 SS unrelated non-Hodgkin's lymphomas, while SS related MESA samples were characterized by an IL-4 negative pattern and lacked IL-3 or IFN-gamma expression in 3/7 cases and in 2/7 cases, respectively. CONCLUSION: Many cytokines may be involved in the evolution of prelymphomatous to definite B cell malignant lesions in SS, as well as in the development of SS unrelated B cell non-Hodgkin's lymphomas. A putative pathobiological role of the IL-12/IL-4 balance, in the presence of cytokines that may sustain B cell proliferation (i.e., IL-3, IL-6, IL-10), may represent a major point for future research. Finally, our data reinforce the view of SS as a human model of B cell lymphomagenesis.

Adult↗

Diagnostic and biological determinants in undifferentiated and poorly differentiated ovarian carcinomas.

Six ovarian undifferentiated carcinomas (UCs) and 19 poorly differentiated serous (14 cases) and endometrioid (5 cases) carcinomas with areas of solid diffuse carcinomas have been considered for the study. Pathological findings were analyzed in conjunction with molecular analysis concerning the structure and expression of nm23-H1 gene. Differences in the frequency of loss of heterozigosity (LOH) of this gene have been observed between the two groups, UCs displaying lower percentage of LOH (1/5) as compared to poorly differentiated tumors (17/17). The remaining 3 cases (1 UC and 2 poorly differentiated carcinomas) were homozygotes, i.e., noninformative. UCs might occur as a consequence of cellular dedifferentiation, being at the end of the differentiation spectrum of epithelial ovarian tumors. Nevertheless, this study suggests that, in a fraction of cases, UCs could represent a distinct entity not involved in the malignant progression, associated with peculiar DNA anomalies, one possibly being that of the nm23-H1 deletion. In other words, a noticeable subset of UCs, not harboring nm23-H1 alterations, may be histologically uncommitted "ab initio". Moreover, nm23-H1 LOHs could be considered early events in the ovarian carcinogenesis, because similar molecular patterns were found both in primary and metastatic sites of the same tumor.

Biomarkers, Tumor↗

Comparison of mechanisms responsible for resistance to idarubicin and daunorubicin in multidrug resistant LoVo cell lines.

Two human colon carcinoma drug resistant clones (LoVo-IDA-1 and LoVo-IDA-2) were selected by continuous pressure of LoVo parent cell lines to idarubicin (IDA). Both cell sublines exhibited a typical multidrug resistance (MDR) phenotype but, despite IDA selection, the resistance index (RIext) was higher for daunorubicin (DAU) (RIext = 101-112) than for IDA (RIext = 20-23). A similar pattern of cross-resistance was also observed in two (DOX) doxorubicin-selected LoVo cell lines (LoVo-DOX-1 and LoVo-DOX-2). All the MDR cell lines exhibited decreased drug accumulation and increased intracellular drug tolerance as evidenced by the greater intracellular amount of drug required to cause a 50% growth inhibition (IC50int) compared to their parent cell line. The differences between DAU and IDA RIext exhibited by MDR cells were a function of intracellular resistance. DAU IC50int was 13.9 and 14.9 times higher in LoVo-IDA-1,2 and 6.4 and 6.2 in LoVo-DOX-1,2 cell lines, respectively, than in LoVo-sensitive cells, whereas IDA IC50int was only 3.6 and 3.2 times higher in LoVo-IDA-1,2 and 2.2 and 2.3 in LoVo-DOX-1,2 cell lines, respectively. Conversely, variations in IDA accumulation between resistant and sensitive cells were similar to those observed for DAU [the ratios between DAU uptake in sensitive and resistant cells were almost identical (P = NS) to those observed for IDA]. Differences between IDA and DAU intracellular distribution accounted for the relatively higher DAU intracellular resistance. In fact nuclear/cytoplasmic (N/C) DAU fluorescence ratio was higher (P < 0.01) in sensitive (N/C = 3.4 +/- 2.7) than in MDR cells (N/C ranging from 0.31 +/- 0.2 to 0.41 +/- 0.1). In contrast, no significant (P = NS) differences were observed in IDA N/C ratios between sensitive and MDR cells (N/C ranging from 0.16 +/- 0.1 to 0.20 +/- 0.1). In MDR cells, 1-hr VER (10 microM) treatment partially reverted both DAU N/C ratios and intracellular DAU resistance but neither changes in IDA N/C ratios nor variation in intracellular IDA resistance were observed following VER exposure. In conclusion, the greater intracellular drug tolerance that MDR cells show for DAU compared to IDA makes IDA more effective than DAU in MDR cells overexpressing P-glycoprotein (P-gp).

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Molecular mechanisms possibly affecting WT1 function in human ovarian tumors.

The frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WT1 gene, a proposed tumor-suppressor gene located on chromosome 11p13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WT1 gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WT1 gene functions as a classical tumor-suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be "exposed" by the observed 11p13 allelic deletions. Expression analysis showed that the WT1 gene was transcriptionally active in all the tumors tested, but considerable variations in the mRNA levels were found. This apparent variability, which should be confirmed at the cellular level in the tumor specimens, was also observed in the ovarian tumor-cell lines. Finally, WT1 expression data were evaluated in conjunction with immunohistochemical data on p53. The possible functional effects of altered WT1 mRNA expression in ovarian tumors are discussed, taking into account the potential WT1/p53 protein interaction.

Adenocarcinoma↗

p53 protein over-expression and p53 gene abnormalities in HIV-1-related non-Hodgkin's lymphomas.

Alteration of the p53 tumor-suppressor gene was studied in non-Hodgkin's lymphomas (NHLs) from HIV-1-infected patients. p53 protein was over-expressed in 10 out of the 45 (22%) cases analyzed, mainly clustering in the small-non-cleaved-cell (SNC) (5/19) and Ki-1+ anaplastic large-cell (ALC) (3/8) sub-types, according to previous findings on HIV-1-unrelated NHLs. p53-positive small-non-cleaved-cell lymphomas presented a diffuse or clustered pattern of p53-positive neoplastic cells consequent upon p53-gene mutations. In contrast, in Ki-1+ ALC lymphomas p53 immunohistochemical reactivity was limited to scattered tumor cells, and no p53-gene alterations could be detected. These results suggest that p53-gene alterations play a role in the lymphomagenetic process of a fraction of HIV-1-related SNC NHLs, however with a frequency no different from that observed in HIV-1-unrelated NHLs of the same sub-type. In HIV-1-related Ki-1+ ALC lymphomas, mechanisms different from gene alterations might be implicated in over-expression of p53 protein.

Base Sequence↗

In vivo phenotypic characteristics of AKR T-cell lymphomas with different leukemic potential: possible role of alpha 4 beta 7 integrin in the progression towards the leukemic phenotype.

The present study was undertaken in order to determine whether the expression of specific surface molecules which mediate immune recognition as well as cell-cell and cell-matrix interactions is associated with the leukemic evolution of T-cell lymphomas. To this end, we have investigated the in vivo phenotypic characteristics and the in vitro natural-killer(NK)-cell susceptibility of a group of MCF-247-induced AKR/J T-cell lymphomas with different leukemic potential. We found that in the AKR/J model, the biological aggressiveness of leukemic cells is not dependent upon an escape from host immune surveillance as a consequence of an in vivo down-regulation of H2-Kk determinants or a resistance to NK lysis. Moreover, NK susceptibility of AKR/J lymphomas does not seem to correlate with the level of H2-antigen expression. No obvious correlation was found between the leukemic phenotype and the amount of MEL-14, LFA-1, ICAM-1, Pgp-1/CD44 and THAM/CD26 antigen expression. An in vivo coordinated up-regulation of alpha 4 and beta 7 integrin chains, with the highest levels of expression detected in secondary sites of leukemic infiltration, was observed in the highly leukemic lymphoma NQ22 and, albeit to a lesser extent, in lymphomas with moderate leukemic potential. Conversely, non-leukemic lymphomas were repeatedly alpha 4- and beta 7-negative. These findings suggest that in the AKR/J system the expression of alpha 4 beta 7 integrin may contribute to leukemic spreading of T-cell lymphomas.

Animals↗

High frequency of Epstein-Barr virus latent membrane protein-1 expression in acquired immunodeficiency syndrome-related Ki-1 (CD30)-positive anaplastic large-cell lymphomas. Italian Cooperative Group on AIDS and Tumors.

Immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-1 (LMP-1) was used to identify EBV-associated Ki-1-positive anaplastic large-cell (ALC) lymphomas occurring in 11 patients with and 29 patients without human immunodeficiency virus (HIV) infection. In addition, 18 representative cases of other acquired immunodeficiency syndrome (AIDS)-related lymphomas and 66 cases of Hodgkin's disease, including 14 patients with HIV infection, were investigated. In patients with HIV infection, LMP-1 was found more frequently in Ki-1-positive ALC lymphomas than in other histotypes, although the difference in EBV association between Ki-1-positive ALC and other lymphomas was not significant. In these patients, the percentage of LMP-1 expressing Ki-1-positive ALC lymphomas was significantly higher than that found in patients without HIV infection (72.7% vs. 24.1%; P < .01), thus suggesting an etiologic role for EBV in a large proportion of AIDS-related Ki-1-positive ALC lymphomas. Moreover, the frequency of LMP-1 expression in Hodgkin's disease cases (71.4% in patients with and 21.1% in patients without HIV infection) was close to that found in Ki-1-positive ALC lymphoma cases, supporting the view that the higher frequency of EBV association with both entities detected in patients with HIV infection may be AIDS-related.

Humans↗

Human herpesvirus 6: a survey of presence and variant distribution in normal peripheral lymphocytes and lymphoproliferative disorders.

The presence and distribution of human herpesvirus 6 (HHV-6) variants was investigated by polymerase chain reaction in samples from healthy donors and biopsies from non-Hodgkin's lymphomas and Hodgkin's disease. HHV-6 DNA was present in peripheral blood lymphocytes of 17% of healthy donors, variant B three times more frequently than A. HHV-6 was not present in 35 non-Hodgkin's lymphomas of B cell origin and was in only 1 of 10 non-Hodgkin's lymphomas in AIDS patients. HHV-6 DNA was present in 29% of Hodgkin's disease samples; variant B was more frequent than A. Epstein-Barr virus DNA was detected in 38% of Hodgkin's disease biopsies and did not correlate with HHV-6. Thus, the two HHV-6 variants are differently distributed in the healthy population, and the virus probably has no direct role in the development of B cell non-Hodgkin's lymphoma. The detection of HHV-6 DNA in about one-third of Hodgkin's disease biopsies suggests that HHV-6 might be associated with a subset of this disorder.

DNA, Viral↗

P53 overexpression in human soft tissue sarcomas: relation to biological aggressiveness.

BACKGROUND: The tumor suppressor protein p53 is overexpressed in a large fraction of human tumors. It has been supposed that p53 abnormalities may be an early event that contributes to the neoplastic transformation; alternatively, p53 overexpression might be related to progression toward more aggressive tumor phenotypes. The aim of the present work was to better clarify the role of p53 overexpression in human soft tissue sarcomas (IISTS). DESIGN: p53 immunohistochemistry analysis using the Pab 1801 was performed in frozen samples of HSTS obtained from 61 patients. Tumors were classified according to the WHO criteria, histologic grading was based on the criteria of Enzinger and Weiss, and DNA ploidy and S-phase determination was performed by flow cytometrical analysis. RESULTS: Of all the HSTS we analyzed, p53 protein over-expression occurred more frequently in G3 grade tumors (p < 0.01), HSTS of III A-B stage (p = 0.02) and in aneuploid tumors (p < 0.01). CONCLUSIONS: The association of p53 overexpression with parameters of biological aggressiveness suggests an involvement of p53 in the neoplastic progression of HSTS. This assumption is supported by the findings that in tumors with a mixed diploid/aneuploid neoplastic cell population p53 protein expression was significantly (p < 0.01) higher in the aneuploid cell subpopulation. In conclusion, our study suggests that overexpression of p53 is present mainly in the most biologically aggressive forms of HSTS and may therefore represent a neoplastic progression index possibly useful for prognostic purposes.

DNA, Neoplasm↗

The polymerase chain reaction detects B cell clonalities in patients with Sjögren's syndrome and suspected malignant lymphoma.

OBJECTIVE: To investigate the usefulness of the polymerase chain reaction (PCR) to detect B cell clonal expansions in tissues where lymphoproliferative disease was suspected in the course of Sjögren's syndrome (SS). METHODS: Tissue samples from 7 patients with definite (5 cases) or probable (2 cases) SS were subjected to routine histopathologic studies, immunophenotyping, and genotypic analysis, including Southern blotting and PCR amplification of immunoglobulin heavy chain (IgH) variable-diversity-joining (VDJ) region gene rearrangements. RESULTS: Malignant lymphoma was detected in 3 cases, and myoepithelial sialadenitis in the remaining 4. B cell clonal expansion was detected in 7/7 cases by PCR, 5/7 by Southern blotting, and in no case of myoepithelial sialadenitis by kappa/lambda light chain immunophenotyping. CONCLUSION: PCR may represent a quick and powerful tool to detect B cell clonalities in SS. Such information may provide new insights into the pathogenesis of the disease and may improve the clinical approach to the patients.

Adult↗

Ultraviolet-induced p53 mutations in atypical fibroxanthoma.

Atypical fibroxanthoma (AFX) is an uncommon neoplasm of the superficial soft tissue occurring in actinically damaged skin of elderly patients. Sun-exposed skin also represents the main site of squamous and basal cell carcinomas and malignant melanoma, and a key role for ultraviolet (UV) radiation in their pathogenesis has long been suspected. UV-related mutations of the p53 gene have been identified in human skin cancers. To verify whether the pathogenesis of AFX is related to the effect of sunlight, p53 protein and gene status have been investigated in a series of 10 cases of AFX. Seven of 10 showed p53 immunoreactivity in most of the neoplastic cells. Molecular analysis of the p53 gene revealed an abnormal single strand conformation polymorphism pattern in all the p53 positive cases. Polymerase chain reaction direct sequencing revealed that all the mutations involved cytosine bases. Four cases showed C to T transitions (including two CC-TT double base substitutions) and two cases showed C to G transversion. All but one mutation took place at dipyrimidine sites. These findings provide the first objective evidence for the central role of UV radiation in the development of AFX and also represent the first in vivo demonstration of solar UV-induced mutations in a human mesenchymal neoplasm.

Base Sequence↗

Three discrete regions of deletion at 3p in head and neck cancers.

Alteration of the short arm of chromosome 3 is one of the most consistent cytogenetic abnormalities found in human head and neck cancers. These alterations, composed of translocations and deletions, have been associated with the presence of a tumor suppressor gene(s), but no clear evidence of the location of this presumptive gene(s) was available. We performed a molecular analysis of the 3p region using a polymerase chain reaction-based approach. Twenty-eight of the 38 cases analyzed (74%) showed the presence of single or multiple areas of allelic loss. Three commonly deleted regions, tentatively mapped to 3p24-ter, 3p21.3, and 3p14--cen, were identified. Our results suggest that at least three oncosuppressor genes mapping on 3p may be involved in head and neck cancer development and support a common oncogenic pathway with squamous cell lung cancer, for which a similar pattern of 3p deletion has been described recently.

Base Sequence↗

Subtypes of Epstein-Barr virus in HIV-1-associated and HIV-1-unrelated Hodgkin's disease cases.

Epstein-Barr virus (EBV) type 2 is considered to be a much less potent transformer of lymphocytes than type 1. However, type-2 EBV may be involved in the pathogenesis of non-Hodgkin's lymphomas (NHLs) arising in immunocompromised patients, i.e., subjects with malaria or HIV-1 infection. To determine whether type-2 EBV may also play a role in Hodgkin's disease (HD) developing in immunocompromised patients, we characterized EBV subtypes in EBV-positive HD samples from 10 HIV-1-positive patients as well as from a control population of 24 HIV-1-negative patients. Type-2 EBV was detected in 5/10 HD samples from the HIV-1-positive group (1 case showed concomitant type-1 EBV positivity), but only in 1/20 HD samples from the HIV-1-negative group, indicating that, during HIV-1-induced immunodepression, type-2 EBV may be pathogenetically involved also in HD, as previously reported for HIV-associated NHLs.

Base Sequence↗

High incidence of monoclonal EBV episomes in Hodgkin's disease and anaplastic large-cell KI-1-positive lymphomas in HIV-1-positive patients.

A series of selected lymphoid malignancies (LMs) occurring in Italian HIV-1-infected (HIV+) patients, principally intravenous drug users, was investigated. In addition to small non-cleaved-cell (SNCC) and large-cell immunoblastic (LCI) non-Hodgkin's lymphomas (NHLs), a relatively high occurrence of anaplastic large-cell Ki-I-positive (ALC Ki-I+) lymphomas and Hodgkin's disease (HD) was observed, at variance with other reported series of HIV+ patients. Combined results of in situ hybridization and Southern-blot analyses, in conjunction with immunohistochemical detection of Epstein-Barr virus (EBV)-encoded latent membrane protein-I (LMP-I), showed an almost complete association of ALC Ki-I+ lymphomas and HD cases with EBV. The neoplastic cells of both these LMs also showed common immunophenotypic features such as frequent absence of B- and T-cell differentiation markers and expression of the Ki-I activation marker, while SNCC and LCI lymphomas were mainly of mature B-cell origin and Ki-I-. The concomitant high incidence of ALC Ki-I+ lymphomas and HD in a specific group of HIV+ patients, their almost complete association with EBV in clonal and episomal form and the great similarity in differentiation, activation and virological markers which they display suggest that these LMs are pathological variants of a continuous spectrum of HIV-I-associated disorders etiopathologically linked to EBV.

Antigens, CD↗