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Biomedical subjects

Erica Travaglino

Publications and source records attributed to Erica Travaglino.

15 recordsLinked to original sources
PubMed2026

Comprehensive Clinicopathologic, Immunohistochemical, and Genomic Profiling of Sporadic Ampullary Somatostatin-producing D-cell Neuroendocrine Tumors Identifies Recurrent HRAS Hotspot Mutations.

Ampullary somatostatin-producing D-cell neuroendocrine tumors are rare neoplasms that may be associated with type 1 neurofibromatosis. The molecular features of sporadic ampullary somatostatin-producing D-cell neuroendocrine tumors (SAMSOM-NETs) remain poorly characterized. We performed an integrated morphological, immunohistochemical, and genomic analysis of a multicenter series of SAMSOM-NETs. Eleven cases were included (73% male; median age: 63 years). All six patients who underwent lymphadenectomy were staged as pN1, and liver metastases were found in three cases; however, no tumor-related deaths occurred (median follow-up: 104 months). Common histologic features that can pose diagnostic challenges in the differential diagnosis with adenocarcinoma included a tubulo-glandular architecture (100%), periodic Acid-Schiff (PAS)-positive intraluminal mucin (73%), MUC1 expression (100%), and carcinoembryonic antigen (45%) expression. All tumors exhibited dot-like cytoplasmic reactivity for cytokeratins (CK) CAM5.2 or CK AE1/AE3, and 82% were CK7-positive. ISL1 and PDX1 were diffusely expressed in all cases, while CDX2 was positive in 54% and ARX showed only focal expression in four tumors. Genomic profiling revealed microsatellite stability and low tumor mutational burden. Alterations in the RAS pathway, including HRAS mutations (4 cases, 36%), a KRAS mutation (1 case), and NF1 alterations (one case), were identified in 54% of cases and in all tumors with liver metastases. Additional molecular findings included a CDK12 splice-site alteration and an NTRK3::PRDM4 fusion. Potentially actionable alterations affecting kinase-related pathways were detected in 64% of tumors. Our findings support SAMSOM-NET as a peculiar neuroendocrine tumor subtype showing distinctive histologic and molecular characteristics with potential diagnostic and therapeutic implications.

Humans↗
PubMed2006

Survivin expression, apoptosis and proliferation in chronic myelomonocytic leukemia.

We analyzed the expression of the inhibitor of apoptosis survivin by immunocytochemistry in bone marrow cells from patients with chronic myelomonocytic leukemia (CMML) to evaluate possible abnormalities in comparison with other myelodysplastic (MDS) and myeloproliferative syndromes, and to investigate a possible correlation between survivin expression and altered apoptosis or proliferation, or relevant laboratory and clinical findings. Thirty-four patients with CMML [18 MDS-CMML and 16 myeloproliferative disorder (MPD)-CMML], 90 with MDS, 41 with acute myeloid leukemia (AML), 19 with chronic MPD and 25 control subjects were studied. In normal samples survivin was never detectable. In CMML survivin levels higher than in MDS and AML (P < 0.0001), but similar to those found in MPD were observed. In CMML and MDS apoptosis was significantly higher compared to normal controls and all other subtypes of leukemias (P < 0.0001). Proliferation did not differ significantly in normal controls, MDS and CMML; the lowest levels were observed in AML and MPD (P < 0.0001). In CMML there was no correlation between survivin expression and blast cell percentage, apoptosis or proliferation, FAB or WHO subgroup. Proliferation was higher in MDS-CMML and tended to correlate with overall survival. CMML-2 cases with higher survivin expression showed higher evolution rate and shorter survival. In conclusion, CMML is characterized by high proliferation and apoptosis. Survivin overexpression, by disrupting the balance between cell proliferation/differentiation and apoptosis, may play an important role in its pathophysiology. The detection of survivin-deregulated expression may provide a useful tool for diagnosis, prognosis and a possible target for experimental treatments.

Acute Disease↗
PubMed2005

Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making.

PURPOSE: The aim of this study was to evaluate the prognostic value of the WHO proposal, to assess the role of the main prognostic factors in myelodysplastic syndromes (MDSs) classified into WHO subgroups, and to estimate mortality (standardized mortality ratio [SMR]) and life expectancy in these groups as a basis for clinical decision making. PATIENTS AND METHODS: Four hundred sixty-seven patients who were diagnosed as having de novo MDS at the Division of Hematology, University of Pavia (Pavia, Italy), between 1992 and 2002, were evaluated retrospectively for clinical and hematologic features at diagnosis, overall survival (OS), and progression to leukemia (leukemia-free survival). RESULTS: Significant differences in survival were noted between patients with refractory anemia (RA), refractory cytopenia with multilineage dysplasia, RA with excess blasts, type 1 (RAEB-1), and RAEB-2. The effect of demographic factors on OS was observed in MDS patients without excess blasts (age, P = .001; sex, P = .006), as in the general population. The mortality of RA patients 70 years or older did not differ significantly from that of the general population (SMR, 1.62; P = .06). Cytogenetics was the only International Prognostic Scoring System variable showing a prognostic value in MDS classified into WHO subgroups. Transfusion-dependent patients had a significantly shorter survival than patients who did not require transfusions (P < .001). Developing a secondary iron overload significantly affected the survival of transfusion-dependent patients (P = .003). CONCLUSION: These data show that the WHO classification of MDSs has a relevant prognostic value. This classification, along with cytogenetics, might be useful in decisions regarding transplantation. MDS with isolated erythroid lineage dysplasia identifies a subset of truly low-risk patients, for whom a conservative approach is advisable.

Adult↗
PubMed2005

Aberrant mitochondrial iron distribution and maturation arrest characterize early erythroid precursors in low-risk myelodysplastic syndromes.

Early erythroblasts from patients with refractory anemia (RA) and RA with ringed sideroblasts (RARS) show constitutive mitochondrial release of cytochrome c. Moreover, mature erythroblasts in RARS, but not in RA, display aberrant accumulation of mitochondrial ferritin (MtF). We analyzed cytochrome c release, MtF expression, and gene expression during erythroid differentiation in bone marrow cells from myelodysplastic syndrome (MDS) patients and healthy controls. Whereas none or few cultured erythroid cells from healthy individuals and RA patients expressed MtF, those from RARS patients showed MtF expression at an early stage, when cells were CD34+ and without morphologic signs of erythroid differentiation. The proportion of RARS erythroblasts that were MtF+ increased further upon in vitro maturation. Moreover, a significant overexpression of mRNA encoding cytochrome c, and proapoptotic Bid and Bax, was seen in freshly isolated cells from MDS patients. Genes involved in erythroid differentiation were also dysregulated in MDS cells. Importantly, GATA-1 expression increased during normal erythroid maturation, but remained low in MDS cultures, indicating a block of erythroid maturation at the transcriptional level. In conclusion, aberrant MtF expression in RARS erythroblasts occurs at a very early stage of erythroid differentiation and is paralleled by an up-regulation of genes involved in this process.

Adenosine Triphosphate↗
PubMed2005

Thalidomide treatment reduces apoptosis levels in bone marrow cells from patients with myelodysplastic syndromes.

We treated with thalidomide seven patients with primary MDS and observed reduction of the transfusion requirement in three cases and reduction of bone marrow blasts in one case. The apoptotic rate of bone marrow cells diminished significantly from a mean of 43.8% to a mean of 17.5%, whereas the proliferative activity did not change. Plasma TNF-alpha, bFGF, IL-1beta levels decreased variably, whereas VEGF levels tended to increase. Matrix metalloproteinases 2 and 9 expression decreased in bone marrow cells of responders. A reduction of CD4 cells and an increase of NK cells was observed in the peripheral blood. Thus, thalidomide may produce a fairly good hematological improvement in erythroid series in MDS, with complex biological mechanisms.

Aged↗
PubMed2005

Overexpression of the Doppel protein in acute myeloid leukaemias and myelodysplastic syndromes.

We investigated the expression patterns and distribution of Doppel (Dpl), the product of the prion-like gene PRND, in the leukaemic cell lines HL-60 and K562 and in bone marrow cells from 44 patients with acute myeloid leukaemia (AML) and 63 patients with myelodysplastic syndrome (MDS). Whereas normal samples were negative or showed very weak expression that was restricted to CD34(+) cells, Dpl was detected in both cell lines and in most AML and MDS cases by immunocytochemistry and Western blotting. Quantitative reverse transcription polymerase chain reaction revealed variable mRNA levels in almost all AML and MDS cases, but barely detectable levels in normal bone marrow. These differences were confirmed by in situ hybridization. PRND expression was higher in advanced compared with early MDS (P = 0.01), but Dpl levels did not predict disease progression. In AML there was no correlation between Dpl levels and clinical or laboratory findings. In conclusion, this is the first time that the expression of PRND has been demonstrated in human bone marrow. The molecular mechanism of the observed overexpression is unknown; however, the differential Dpl distribution in AML and MDS versus healthy subjects makes it a possible leukaemia-associated antigen that could be useful for diagnostic and therapeutic purposes.

Acute Disease↗
PubMed2004

Survivin expression in acute leukemias and myelodysplastic syndromes.

We analyzed by immunocytochemistry the expression of survivin in bone marrow cells from 36 acute myeloid leukemia (AML) cases, from 98 patients with myelodysplastic syndrome (MDS), and from 41 non hemopathic subjects. Our aim was to evaluate whether abnormalites in survivin expression were associated with peculiar laboratory and clinical findings, altered apoptosis levels or altered proliferative rate. In normal samples survivin was never detectable. It was detected in almost all AML and MDS cases. In AML and in MDS with more than 5% bone marrow blasts survivin levels higher than in RA and RARS were observed (P=0.04). In MDS a tendential inverse correlation between survivin and TUNEL positivity was identified (P=0.08), whereas survivin expression was independent of the proliferative rate. Survivin levels did not predict disease progression in MDS; among AML patients treated with intensive polichemotherapy, survivin expression was significantly higher in resistant cases (P=0.01). Our findings confirm the high incidence of survivin expression in AML. Its abnormal expression also in MDS may play a role in promoting aberrantly increased cell viability and contribute to the altered homeostatic balance between cell growth and cell death.

Apoptosis↗
PubMed2003

Apoptosis in relation to CD34 antigen expression in normal and myelodysplastic bone marrow.

An increased bone marrow (BM) apoptosis is one of the mechanisms responsible for the ineffective hematopoiesis of myelodysplastic syndromes (MDS). It is controversial whether the excessive apoptosis in myelodysplasia predominantly involves the subset of progenitor cells or of maturing cells. We investigated the degree of apoptosis in MDS BM and its differences from normal marrow in relation to CD34 antigen expression. A double-labelling technique that combined the Tdt-mediated dUTP nick end labelling (TUNEL) method with immunocytochemistry for CD34 antigen was used on BM slides of 18 MDS patients and 11 controls. The apoptotic rate (AR) appeared significantly higher in CD34-negative than in CD34-positive cell subsets both in myelodysplastic and in normal BM. When MDS and normal CD34-negative cell populations were compared, a greater AR in MDS CD34-negative cells was found, while no statistical difference in AR resulted from the comparison between MDS and normal CD34-positive cell populations. Our results suggest that in myelodysplastic as well as in normal BM the apoptotic phenomenon predominantly involves the maturing cells. The increase in apoptotic levels which can be observed in myelodysplastic compared to normal BM seems to be mainly due to an increase in apoptosis in the differentiated cell population.

Aged↗
PubMed2002

Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia.

The sideroblastic anemias are characterized by ring sideroblasts, that is, red cell precursors with mitochondrial iron accumulation. We therefore studied the expression of mitochondrial ferritin (MtF) in these conditions. Erythroid cells from 13 patients with refractory anemia with ring sideroblasts (RARS) and 3 patients with X-linked sideroblastic anemia (XLSA) were analyzed for the distribution of cytoplasmic H ferritin (HF) and MtF using immunocytochemical methods. We also studied 11 healthy controls, 5 patients with refractory anemia without ring sideroblasts (RA), and 7 patients with RA with excess of blasts (RAEB). About one fourth of normal immature red cells, mostly proerythroblasts and basophilic erythroblasts, showed diffuse cytoplasmic positivity for HF, but very few were positive for MtF (0%-10%). Similar patterns were found in anemic patients without ring sideroblasts. In contrast, many erythroblasts from patients with sideroblastic anemia (82%-90% in XLSA and 36%-84% in RARS) were positive for MtF, which regularly appeared as granules ringing the nucleus. Double immunocytochemical staining confirmed the different cellular distribution of HF and MtF. There was a highly significant relationship between the percentage of MtF(+) erythroblasts and that of ring sideroblasts (Spearman R = 0.90; P <.0001). Reverse transcription-polymerase chain reaction studies demonstrated the presence of MtF mRNA in circulating reticulocytes of 2 patients with XLSA but not in controls. These findings suggest that most of the iron deposited in perinuclear mitochondria of ring sideroblasts is present in the form of MtF and that this latter might be a specific marker of sideroblastic anemia.

5-Aminolevulinate Synthetase↗
PubMed2002

Clinical and biological effects of treatment with amifostine in myelodysplastic syndromes.

We treated six patients with primary myelodysplastic syndrome (MDS) with amifostine (200 mg/m(2) i.v./three times a week for three consecutive weeks). Neutrophil counts were more frequently increased than platelet and reticulocyte counts, but no reduction of the transfusion requirement was observed. Significant reduction of the marrow blasts was observed in one case of refractory anaemia with excess of blasts. In vitro stimulation of haematopoiesis was observed in five cases. The apoptotic rate of marrow cells was significantly diminished even after the first course. Our findings show fairly good clinical and biological response to amifostine in MDS.

Aged↗