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Biomedical subjects

Claudio Agostinelli

Publications and source records attributed to Claudio Agostinelli.

9 recordsLinked to original sources

Construction and validation of a bone marrow tissue microarray.

BACKGROUND: The use of tissue microarrays (TMAs) is now a generally accepted method for the investigation of solid tumours. However, little is known about the applicability of the TMA technique for analysis of patients with acute leukaemia. A bone marrow (BM)-TMA analysis with 15 different immunohistochemical markers was performed. The TMA was validated by comparison with the corresponding full tissue sections. MATERIALS AND METHODS: A BM-TMA comprising 148 cases of acute leukaemia, including 115 acute myeloid leukaemia (AML) and 33 acute lymphoblastic leukaemia (ALL) cases, was constructed. Expression of CD3, CD10, CD15, CD20, CD34, CD61, CD68, CD79a, CD99, CD117, CD138, myeloperoxidase, haemoglobin A1, glycophorin and terminal deoxynucleotidyl transferase was immunohistochemically analysed. 50 cases of the TMA were directly compared with the corresponding full tissue section to validate the results. RESULTS: Morphologically and immunohistochemically, 6 (4%) of 148 cases and 765 (11%) cores of 6912 individual analyses were not evaluable. A direct comparison of TMA cases with conventional full sections showed a concordance of the results of 100%. CONCLUSIONS: The small size of bone-marrow biopsies and the presence of bony trabeculae do not preclude construction and analysis of acute leukaemia TMAs. Acute leukaemia cases on TMA displayed the characteristic phenotypic profiles expected in different AML and ALL subtypes. Therefore, the TMA technique is also a promising method for high-throughput analysis of combined marker expression and clinicopathological correlations in patients with leukaemia.

Acute Disease↗

Marker expression in peripheral T-cell lymphoma: a proposed clinical-pathologic prognostic score.

PURPOSE: Although peripheral T-cell lymphoma, unspecified (PTCL/U), is the most common T-cell tumor in Western countries, no study to date has been based on the application of a wide panel of markers to a large series of patients and assessed the impact of phenotype on survival. We evaluated the expression of 19 markers in 148 PTCLs/U and 45 PTCLs of the angioimmunoblastic type (AILD). PATIENTS AND METHODS: The analysis was performed on tissue microarrays by immunohistochemistry and in situ hybridization. Clinical data were available in 93 PTCL/U patients, most of whom had been included in a previous study proposing a prognostic index (PIT). RESULTS: An aberrant phenotype with frequent loss of CD5 and/or CD7 was typical for PTCLs, irrespective of whether they were U or AILD. Aberrantly expressed proteins rarely included CD20, CD15, and CD30. Positivity for Epstein-Barr virus-associated small RNAs and CD15 expression emerged as adverse prognostic factors. Among PTCLs/U, the proliferation-associated protein Ki-67 turned out to be prognostically relevant and was integrated in a new predictive score, incorporating age (> 60 years), high lactate dehydrogenase, poor performance status, and Ki-67 > or = 80%. This score was associated with the patient outcome (P < .0001) and was found to be more robust than PIT (P = .0043) in the present series. CONCLUSION: Our retrospective analysis shows a wide range of protein expression in PTCLs and proposes a new prognostic index. The latter represents one of the first examples of mixed score (including patient- and tumor-specific factors) applied to malignant lymphomas and may be the basis for future prospective therapeutic trials.

Adult↗

Successful treatment of disseminated Fusariosis after allogeneic hematopoietic stem cell transplantation with the combination of voriconazole and liposomal amphotericin B.

Fusarium is an opportunistic fungal pathogen which is emerging as a significant cause of morbidity and mortality in the immunocompromised host [Fleming RV, Walsh TJ, Anaissie EJ. Emerging and less common fungal pathogens. Infect Dis Clin North Am 2002;16:915-34]. This disease can be localized, focally invasive or disseminated, when two or more noncontiguous sites are involved. Therapeutic options are scarce and mortality reaches 80-90% in patients subjected to allogeneic hematopoietic stem cell transplant (allo-SCT) [Nucci M, Marr KA, Queiroz-Telles F, Martins CA, Trabasso P, Costa S, et al. Fusarium infection in hematopoietic stem cell transplant recipient. Clin Infect Dis 2004;1237-42]. We report a case of disseminated Fusariosis in a severe immunocompromised patient after allo-SCT that responded to treatment with the early combination of intravenous voriconazole and liposomal amphotericin B.

Adult↗

Potential pathogenetic implications of cyclooxygenase-2 overexpression in B chronic lymphoid leukemia cells.

Evidence suggests that cyclooxygenase-2 (COX-2) increases tumorigenic potential by promoting resistance to apoptosis. Because B chronic lymphoid leukemia (B-CLL) cells exhibit a defective apoptotic response, we analyzed CD19(+) B lymphocytes purified from the peripheral blood of B-CLL patients. Microarray analysis showed a variable (up to 38-fold) increase in the steady-state mRNA levels of COX-2 in B-CLL lymphocytes compared with normal CD19(+) B lymphocytes. The up-regulation of COX-2 in B-CLL cells was confirmed by reverse transcriptase-polymerase chain reaction and Western blot analyses. Moreover, immunohistochemical analysis of B-CLL bone marrow infiltrates confirmed clear expression of COX-2 in leukemic cells. Ex vivo treatment with the COX-2 inhibitor NS-398 significantly decreased the survival of leukemic cells by increasing the rate of spontaneous apoptosis in 13 of 16 B-CLL samples examined, but it did not affect the survival of normal lymphocytes. Pretreatment with NS-398 significantly potentiated the cytotoxicity induced by chlorambucil in 8 of 16 B-CLL samples examined. Moreover, although recombinant tumor necrosis factor-related apoptosis inducing ligand (TRAIL)/Apo2L showed little cytotoxic effect in most B-CLL samples examined, pretreatment with NS-398 sensitized 8 of 16 B-CLL samples to TRAIL-induced apoptosis. Taken together, our data indicate that COX-2 overexpression likely represents an additional mechanism of resistance to apoptosis in B-CLL and that pharmacological suppression of COX-2 might enhance chemotherapy-mediated apoptosis.

Aged↗

Histopathology of B-cell chronic lymphocytic leukemia.

Histologic and immunohistologic findings of B-cell chronic lymphocytic leukemia/small lymphocytic leukemia are revised in the light of the more recent knowledge on the pathobiology of the disease. The guidelines for the optimal handling of the bioptic samples are provided. The relevance of the examination of trephines and surgical specimens is outlined with special reference to the identification of risk factors in individual patients.

Biopsy↗