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Biomedical subjects

F Menestrina

Publications and source records attributed to F Menestrina.

At least 37 records · Page 2Linked to original sources

Differential expression of p57kip2, a maternally imprinted cdk inhibitor, in normal human placenta and gestational trophoblastic disease.

Evidence has recently been provided to support a role for genomic imprinting in the regulation of embryonic implantation and development and placental growth, as well as in the pathogenesis of proliferative trophoblastic diseases. The cyclin-dependent kinase inhibitor p57KIP2 has recently been recognized as a maternally imprinted gene. We investigated p57KIP2 expression in first-trimester normal placentas from interrupted pregnancy, spontaneous abortions, and different types of proliferative trophoblastic diseases using single- and double-marker immunohistochemical techniques. In normal placenta, nuclear p57KIP2 expression was observed at high frequency (up to 100%) in extravillous trophoblast, cytotrophoblast, and implantation-site interstitial trophoblast, but was absent in syncytiotrophoblast. p57KIP2 was also expressed in the stromal cells of maternal decidua, which was one of the few adult tissues retaining p57KIP2 expression (most other adult tissues investigated were negative). p57KIP2 expression was either absent or low in all cases of diploid/tetraploid complete moles (20 cases) and in three cases of gestational choriocarcinoma. On the other hand, all spontaneous abortions (12 cases) and triploid partial moles (19 cases) showed p57KIP2 levels comparable to those observed in normal placenta. These findings are in line with the hypothesis that deregulation of genomic imprinting, particularly the loss of cell-cycle inhibitors such as p57KIP2, is involved in the abnormal development of androgenetic trophoblastic proliferations. In addition, this simple immunohistochemical analysis could provide a useful diagnostic marker in difficult cases.

Choriocarcinoma↗

bcl-2 expression in pleural and extrapleural solitary fibrous tumours.

This study evaluated the immunoreactivity for bcl-2, a molecule involved in the control of programmed cell death, in cases of pleural (14) and extrapleural (2) solitary fibrous tumour (SFT), malignant mesotheliomas of different histological types, and a variety of extrapleural CD34-positive and CD34-negative spindle-cell tumours. In all SFTs, strong and diffuse immunostaining was demonstrated with anti-bel-2 antibody, sharply contrasting with the complete lack of staining observed in all mesotheliomas. The specificity of immunodetection of bcl-2 in SFT was confirmed by immunoblot analysis, showing a band consistent with the bcl-2 protein. At extrapleural locations, strong bcl-2 immunoreactivity was observed in Schwannoma (2/3 cases), synovial sarcoma (4/4 cases), and all cases of CD34-positive gastrointestinal stromal tumour (GIST; 10/10 cases). Most sarcomas were bcl-2-negative. Lack of bcl-2 expression was demonstrated in tumours which can pose problems in the differential diagnosis of SFT and can exhibit haemangiopericytoma-like features, including haemangiopericytoma (3 cases), dermatofibrosarcoma protuberans (16 cases), and deep-seated fibrous histiocytoma (3 cases). The constitutive expression of bcl-2 in SFT widens the spectrum of available markers for these tumours, providing a useful adjunct to their differential diagnosis in difficult cases at pleural and extrapleural sites, and contributing to the understanding of their histogenesis and molecular pathogenesis.

Adult↗

p21/WAF1 cyclin-kinase inhibitor expression in non-Hodgkin's lymphomas: a potential marker of p53 tumor-suppressor gene function.

p21WAF1 (wild-type p53-activated fragment 1) is involved in the control of mammalian cell cycle through the binding and inhibition of cyclin-dependent kinases (Cdk). Because the product of WAF1 gene is a potent downstream effector of the p53 tumor-suppressor gene function, its pattern of cellular expression might correlate with nuclear accumulation of p53-encoded protein and/or p53 gene mutations occurring in malignant lymphomas. To investigate this issue, we analyzed immunohistochemically the expression of p53 and p21WAF1 proteins in tissue involved by non-Hodgkin's lymphomas (NHLs;253 cases) of various histologic types. In a proportion of them (80 cases), we also investigated the possible presence of p53 gene mutations using single-strand conformation polymorphism analysis and direct DNA sequencing. The absence of both p21WAF1 and p53 proteins was observed in 147 of 217 cases (67.7%) among CD30-NHL and in only 8 of 36 (22.2%) CD30+cases, which were mostly anaplastic large-cell lymphomas. A consistent number (> 10%) of p21WAF1-expressing cells was shown in 48 of 253 (18.9%) NHL cases, with a higher incidence in CD30+cases (25/36 [69.4%]), which mostly (21/36) coexpressed p53. These latter cases were characterized by a germline configuration of the p53 gene. In 50 of 253 NHL samples (19.7%), 47 of which (21.6%) belong to the CD30-group, neoplastic cells were p53+/p21-. In all of these cases, the p53+cells accounted for more than 50% of neoplastic cells, up to 100%. Point mutations of p53 gene were solely observed in all investigated cases with this latter phenotype. Our findings strongly suggest that the combined immunohistochemical evaluation of p53 and p21WAF1 is a valuable means of assessing the functional status of the p53 tumor-suppressor gene product in NHL with potential application in the monitorage and prognostication of individual cases.

Biomarkers↗

Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease.

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase-polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.

Anaplastic Lymphoma Kinase↗

Carcinoma-like signet-ring cells in gastric mucosa-associated lymphoid tissue (MALT) lymphoma.

We noticed the presence of epithelial signet-ring cells (SRCs) in a proportion of primary gastric B-cell lymphomas, and in some endoscopic biopsies we found it difficult to decide whether they represented an associated carcinoma. To evaluate the frequency and nature of this phenomenon, we reviewed 108 stomachs resected for primary lymphoma, including 70 mucosa-associated lymphoid tissue (MALT) and 38 non-MALT lymphomas. We found SRCs, either isolated or grouped in clusters, in 26 of 70 MALT lymphomas. The SRCs were always localized in the superficial portion of the lamina propria and associated exclusively with lymphomatous areas. Isolated and scarce SRCs were also found in four of 22 cases of polyclonal atypical lymphoid hyperplasia. Our data suggests that SRCs occurring in gastric MALT lymphomas represent a particular type of LEL in which the foveolar cells disaggregated by the lymphomatous infiltration acquire a globoid, signet-ring appearance. These "foveolar" LELs are found in 37% of MALT lymphomas and are usually associated with the more classic and constant "neck" LELs, which are localized between the foveolae and mucopeptic glands. An awareness of the existence of the foveolar LEL may help avoid overdiagnosis of SRC carcinoma on gastric endoscopic biopsies.

Adult↗

[Sarcoidosis].

Explore the source record for details and available documents.

Granuloma↗

Anti-inflammatory potency and gastrointestinal toxicity of a new compound, nitronaproxen.

Naproxen and its derivative nitronaproxen at the doses of 5 and 10 mg kg-1 were compared for their acute anti-inflammatory efficacy in a carrageenan oedema model and gastrointestinal toxicity in rats. Moreover, the effects of the two drugs were evaluated in the adjuvant arthritis, after chronic doses of 4 and 8 mg kg-1 administered orally for 18 days. The oedema reduction was maintained much longer (until 5 h) with nitronaproxen; the inhibition of arthritis was 50% or more with both doses of the examined drugs. From the histological examination of the stomachs, an extensive mucosal vasocongestion and haemorrhagic lesions have been observed in some rats treated with naproxen. The percentages of animals with ulcers were 50, 100 and 10 with naproxen 6 and 18 mg kg-1 and nitronaproxen 54 mg kg-1 respectively. A better gastrointestinal tolerability has been observed in arthritic and oedemic rats treated with nitronaproxen compared to naproxen: this could be due to the presence of nitric oxide that acts in maintaining the tissue perfusion and integrity.

Animals↗

Synchronous primary hepatic lymphoma and epidermoid lung carcinoma treated with chemotherapy and surgery.

While involvement of the liver by non-Hodgkin's lymphoma is a relatively frequent event, primary liver lymphoma is an uncommon disease. We describe a case of synchronous primary hepatic lymphoma and epidermoid lung carcinoma occurring in a 61-year-old male patient. Complete remission of both diseases was achieved with a radical approach, which included combination chemotherapy and surgery. The patient has now been in persisting complete remission for 40 months after surgery.

Antineoplastic Combined Chemotherapy Protocols↗

Routine application of polymerase chain reaction in the diagnosis of monoclonality of B-cell lymphoid proliferations.

We evaluated four polymerase chain reaction (PCR) methods for their efficiency in detecting monoclonality in a well-characterized panel of frozen and paraffin-embedded B-cell lymphoid proliferations. These approaches (referred to as FR3, FR3A, FR2, and FR1) are based on amplification of rearranged immunoglobulin heavy chain genes, using primers recognizing framework regions I, II, or III. FR3, FR3A and FR2 approaches reproducibly detected monoclonality in 51%, 72%, and 67% of DNAs from frozen lymphomas, respectively. No false-positives were observed. The combination of FR2 and FR3A methods raised the figure to 85%. Comparable results were obtained using paraffin-embedded lymphomas. Reproducibility of FR1 approach was unsatisfactory. The efficiency of all PCR approaches varied depending on lymphoma type. The highest detection rate was in small/intermediate cell and the lowest in centro-follicular lymphomas. Limiting dilution assays showed that PCR methods were able to detect monoclonal B-cell DNA representing 5% of nonlymphoid and 20% of polyclonal B-cell DNA. A diagnostic protocol may include quick and cost-effective PCR screening, particularly in cases of undetermined small cell lymphoid proliferations observed in fine needle aspirates or endoscopic biopsies. This would also reduce call-up of patients to obtain unfixed biopsies.

Base Sequence↗

CD30/Ki-1-positive lymphoproliferative disorders of the skin--clinicopathologic correlation and statistical analysis of 86 cases: a multicentric study from the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group.

PURPOSE: Recently, it has been shown that CD30 antigen expression is associated with a relatively favorable prognosis in primary cutaneous large-cell lymphomas (CLCLs). However, prognostic subsets within the CD30+ group have been difficult to identify due to lack of uniform clinicopathologic and immunophenotypic criteria, limited clinical information, and the inclusion of relatively few patients for statistical analysis in prior studies. To address these problems, we formed a multicentric study group of pathologists and dermatologists to classify and evaluate 92 cases of CD30+ cutaneous lymphoproliferative disorders. PATIENTS AND METHODS: An expert panel established consensus diagnoses for 86 CD30+ cutaneous lymphomas. Cases, clinically and histologically classified as lymphomatoid papulosis (LyP), anaplastic large-cell lymphoma (ALCL), nonanaplastic lymphoma, and borderline histology between LyP and ALCL, were then analyzed statistically by univariate, multivariate, and Cox regression model analysis of potential prognostic features. RESULTS: Spontaneous regression and age less than 60 years were associated with a favorable prognosis, while extracutaneous disease and age greater than 60 had a poor prognosis. Patients with LyP had the best prognosis, followed by those with primary CD30+ lymphomas, regardless of cytologic type (anaplastic or nonanaplastic). Borderline cases, morphologically indistinguishable from LyP and CD30+ ALCL, had a favorable prognosis, similar to LyP. CONCLUSION: Our findings indicate that CD30+ cutaneous lymphoproliferative disorders comprise a spectrum of closely related skin lesions, which can be assigned a relatively favorable or unfavorable prognosis by a combined clinical and pathologic analysis.

Adolescent↗

Serum levels of the soluble form of CD30 molecule as a tumor marker in CD30+ anaplastic large-cell lymphoma.

PURPOSE: To determine serum levels of the soluble form of CD30 molecule (sCD30) in patients with Ki-1/CD30+ anaplastic large-cell lymphoma (ALCL), and to evaluate its correlation with clinical features at presentation and its possible role as a tumor marker to monitor response to treatment and subsequent follow-up. PATIENTS AND METHODS: sCD30 serum levels were measured with an improved commercial sandwich enzyme-linked immunosorbent assay (ELISA) test kit in 24 patients with CD30+ ALCL at diagnosis and in 13 after treatment. RESULTS: Increased values (> 20 U/mL) at diagnosis were observed in 23 of 24 cases (median, 842.5 U/mL; range, 16 to 37,250) as compared with controls (P < .0001). These values were greater than those of 60 stage-matched cases of Hodgkin's disease (HD) (P < .0001). The highest median value was observed in patients with T-cell-type ALCL (1,690 U/mL), with a significant overall difference as compared with B- and null-cell types (P = .004). Phenotype maintained its significance when results were corrected for other parameters, such as age, sex, and stage (P = .03). sCD30 values returned to the normal range in complete remission (CR), but remained increased in one patient who only partially responded to treatment. Subsequent increases of sCD30 levels were recorded in four of four patients after relapse. CONCLUSION: sCD30 appears to be a new biologic serum tumor marker of possible use in the clinical setting of CD30+ ALCL.

Adolescent↗

Nodular lymphocyte predominant Hodgkin's disease and anaplastic large-cell (CD30+) lymphoma: distinct entities or nonspecific patterns?

After many years of frustrating discussion concerning the nature of Hodgkin's and Reed-Sternberg cells and their role in the pathogenesis of Hodgkin's disease, interesting new information has recently been gathered through the use of new technologies. In light of these studies, Hodgkin's disease emerges as a heterogeneous disorder in which some separate new entities may be elucidated, such as nodular lymphocyte predominance Hodgkin's disease and anaplastic large-cell CD30+ lymphoma. In this review, we focus on the morphologic, phenotypic, molecular, and clinical features that have served to partially clarify controversial issues.

Biomarkers, Tumor↗

Abnormal expression of the p53-binding protein MDM2 in Hodgkin's disease.

The possible involvement of p53 tumor suppressor gene in the pathogenesis of Hodgkin's disease (HD) is suggested by the frequent finding of abnormal accumulation of p53 protein in the nuclei of Reed-Sternberg cells and their variants (H-RS) in a large proportion of cases. This finding, besides being consistent with the presence of p53 gene mutations, might represent a consequence of the inactivating interaction between p53 and p53-binding proteins such as the product of the MDM2 cellular oncogene. We have examined an unselected series of 77 HD cases of different histologic patterns for the expression of p53 and MDM2 proteins, using specific monoclonal antibodies and sensitive immunohistochemical techniques in single- and double-marker combination. In the large majority of cases (66/77), a variable proportion of H-RS cells expressed MDM2 that was strictly confined to the nuclei. Coexpression of both MDM2 and p53 was common in the same cells. The abnormal nuclear expression of p53 and MDM2 did not seem to correlate with the presence of Epstein-Barr virus infection, as shown by the results of LMP-1 antigen expression and EBER in situ hybridization analysis. Our data suggest that the abnormal accumulation of MDM2 and p53 proteins in HD might reflect a derangement of molecular mechanisms that could play a pathogenetic role in this disease.

Adolescent↗

Primary gastric CD30 (Ki-1)-positive large cell non-Hodgkin's lymphomas. A clinicopathologic analysis of six cases.

BACKGROUND: The CD30/Ki-1 antigen characterizes a series of non-Hodgkin's lymphomas (NHL) predominantly showing anaplastic large cell (ALCL) morphology and frequently involving the skin and other extranodal sites. In cutaneous large cell lymphomas, the CD30 expression was indicated as a favorable prognostic marker independently from cytology, anaplastic versus nonanaplastic. The stomach is the most common site of extranodal lymphomas in the adult population, but primary gastric CD30+ lymphomas have been reported rarely. METHODS: The clinical, morphologic, and immunohistochemical features of six cases with primary CD30/Ki-1+ gastric large cell lymphomas were analyzed. RESULTS: The mean age of patients was 64 years with a prevalence of women (M:F ration = 1:2). Patients were assigned to Stage IE or IIE. Three of them died of disease, whereas the others are still alive (mean follow-up, 18 months). Three of six cases had ALCL morphology, whereas other cases had centroblastic, immunoblastic, and high-grade mucosa-associated lymphoid tissue lymphoma. Immunohistochemistry revealed a B-cell phenotype in three of six cases; a T-cell phenotype in one of six cases; and a null, non-B, non-T phenotype in two of six cases. CONCLUSIONS: Within CD30+ primary gastric large cell lymphomas, cytology, anaplastic versus nonanaplastic, did not affect clinical presentation and/or prognosis. The survival rate of the patients studied is in keeping with literature reports regarding prognosis of primary high-grade gastric NHL. The findings suggest that clinical behavior of this extranodal lymphoma is more closely related to clinical symptoms and initial stage of disease than to CD30 expression.

Adult↗

Common acute lymphoblastic leukaemia-lymphoma expressing cytokeratin: a case report.

This report presents a case of common acute lymphoblastic leukaemia-lymphoma expressing low molecular weight cytokeratin but no leukocyte common antigen (CD45) in a 57-year-old man. The unusual morphology and clinical course together with the aberrant immunohistochemical results suggested a diagnosis of undifferentiated carcinoma. A detailed immunohistochemistry study on frozen and paraffin sections and molecular analysis prevented a diagnostic mistake.

Antibodies, Monoclonal↗

A rapid immunostaining method for frozen sections.

A simple and rapid one-step method for demonstrating immunohistochemical markers (leukocyte common antigen, cytokeratin, etc.) is described, which can help define the nature of poorly differentiated neoplasms for diagnosis using frozen section. Microwave irradiation was used to speed immunohistochemical analysis using "Enhanced Polymer One-step Staining" (EPOS) reagents on cryostat sections from a variety of pathologic samples. Reproducible results were obtained using EPOS reagents for leukocyte common antigen and cytokeratin. The overall procedure takes less than 10 min and can be completed during surgery.

Frozen Sections↗