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Lluís Colomo

Publications and source records attributed to Lluís Colomo.

10 recordsLinked to original sources
PubMed2006

Unbalanced expression of licensing DNA replication factors occurs in a subset of mantle cell lymphomas with genomic instability.

DNA licensing is a crucial process for chromosome replication control. Deregulation of the licensing factors Cdt1, Cdc6 and the licensing inhibitor geminin has been associated with DNA replication defects and chromosomal instability. We examined the expression of these factors, in mantle cell lymphoma (MCL) and non-neoplastic lymphoid samples, and analysed the potential role of their deregulation in genomic instability. Geminin, Cdt1 and Cdc6 were coordinately expressed in non-neoplastic tissues and most MCL in relationship to the proliferative activity of the cells. However, 6 (18%) tumours showed an unbalanced "licensing signature" characterized by a higher expression of Cdt1 and Cdc6 than the negative regulator geminin. Tumours with this unbalanced signature and p53/p14(ARF) alterations had significantly higher number of chromosome abnormalities than lymphomas with p53/p14(ARF) alterations but with a normal licensing signature. No aberrations of Cdct1, Cdc6, and geminin genes were detected in cases with unbalanced licensing. However, tumours with p53/ARF inactivation and unbalanced licensing signature had significantly higher cyclin D1 levels than tumours with normal licensing signature. These results suggest that an unbalanced mRNA expression of licensing regulatory genes may play a role in the pathogenesis of the chromosomal instability of a subset of MCL with inactivation of the p53/p14(ARF) pathway.

Cell Cycle Proteins↗
PubMed2006

Transesophageal ultrasound-guided fine needle aspiration improves mediastinal staging in patients with non-small cell lung cancer and normal mediastinum on computed tomography.

The aim of the current study was to prospectively assess the value of transesophageal ultrasound-guided fine needle aspiration (EUS-FNA) in the mediastinal staging of patients with non-small cell lung cancer (NSCLC) and CT negative for lymph node (LN) metastases, candidates for surgical resection. EUS-FNA was performed using the standard technique and LNs with at least one morphological feature suggestive of malignancy were sampled. Pathological exam of surgical specimens or tumor positive cytology was used as gold standard. Forty seven patients were included, 21% of whom had advanced disease (pN2) undetected by CT. EUS-FNA demonstrated LN metastases in 50% of them (11% of the whole series), and there were no false positives, resulting in a sensitivity, specificity, positive and negative predictive values and accuracy of 50%, 100%, 100%, 88% and 89%, respectively. In conclusion, EUS-FNA improves mediastinal staging in patients with NSCLC and CT negative for mediastinal nodes. Therefore, EUS-FNA should be considered in any patient with NSCLC and no distant metastases before any therapeutic decision is taken.

Aged↗
PubMed2006

Translocation t(9;14)(p13;q32) in cases of splenic marginal zone lymphoma.

Translocation t(9;14)(p13;q32) involving PAX5 and IGH genes was first described in lymphoplasmacytic lymphoma. New data suggest that this translocation is not restricted to a specific morphologic subtype but occurs in other B-cell lymphomas. We present three cases with a diagnosis of splenic marginal zone lymphoma and t(9;14) confirmed by fluorescent in situ hybridization.

Aged↗
PubMed2005

Immunohistochemical analysis of ZAP-70 expression in B-cell lymphoid neoplasms.

ZAP-70 is a tyrosine kinase that participates in early B-cell differentiation and is a prognostic factor in chronic lymphocytic leukaemia (CLL), where it is associated with an unmutated configuration of the IgV(H) genes. In this study ZAP-70 expression was studied by immunohistochemistry in a spectrum of B-cell lymphoid neoplasms; this staining method was compared with flow cytometry, and the relationship of ZAP-70 expression to mutational status and prognosis was assessed. 242 tissue samples from 225 patients with B-cell lymphoid neoplasms arising at different maturational stages were included. Flow cytometry was performed in all CLL cases (n = 52). IgV(H) mutational status was determined in 25 CLL and 12 mantle cell lymphoma (MCL) patients. ZAP-70 was positive in 34/52 (65%) CLL, 9/31 (31%) Burkitt's lymphoma, 2/7 (29%) lymphoblastic lymphomas, 3/36 (8%) MCL, 1/23 (4%) marginal zone lymphoma, and 1/45 (2%) diffuse large B-cell lymphomas, but in none of the 19 follicular lymphomas or the 14 Hodgkin lymphomas. An identical ZAP-70 pattern was obtained in six patients with simultaneous biopsies from different sites and in 12 patients with sequential biopsies. Immunohistochemistry and flow cytometry gave identical results in 48 the 52 CLLs. All but one ZAP-70-positive CLL had IgV(H) gene in an unmutated configuration, whereas all but one ZAP-70-negative CLL had somatically hypermutated IgV(H). The 12 MCLs analysed were ZAP-70 negative regardless of IgV(H) mutational status (4 mutated, 8 unmutated). ZAP-70 positive CLL was associated with a shorter overall survival (median time 103 months vs. 293 months, p = 0.01) and a shorter time to disease progression (median time 26 months vs. 60 months, p = 0.01). In conclusion, ZAP-70 is expressed in several types of B-cell neoplasm and is easily detected by immunohistochemistry, providing a useful prognostic marker in patients with CLL from whom no other material is available or when other techniques for its assessment cannot be performed.

Adult↗
PubMed2004

Clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-cell lymphomas.

PURPOSE: To determine the clinicopathologic significance and prognostic value of chromosomal imbalances in diffuse large B-cell lymphomas (DLBCL). PATIENTS AND METHODS: We have examined 64 tumors at diagnosis using comparative genomic hybridization and real-time quantitative polymerase chain reaction (PCR), single-stranded conformational polymorphism, and DNA sequencing for the analysis of several potential target genes. RESULTS: The most recurrent alterations were gains of 18q (20%), Xq (15%), 2p, 7q, and 12p (14%), and losses of 6q and 17p (14%). Frequent high-level DNA amplifications were detected at 2p13-p16 and 18q21 loci. Real-time quantitative PCR detected REL and BCL11A gene amplifications in the nine patients with gains at 2p13-p16 and only in one additional patient with normal chromosome 2. Similarly, the BCL-2 gene was amplified in the 12 tumors with gains of 18q21 but in none of 39 patients with normal 18q profile. p53 gene inactivation was detected in nine of 58 (16%) tumors and was commonly associated with 17p losses. Tumors with 18q gains were significantly associated with a high number of chromosomal imbalances, primary nodal presentation, high serum lactate dehydrogenase levels, high International Prognostic Index, shorter cause-specific survival, and a high risk of relapse. Losses of 17p and p53 gene alterations were associated with an absence of complete response achievement. CONCLUSION: These results suggest that DLBCLs have a characteristic pattern of genomic alterations; 18q gains or amplifications and 17p losses are associated with particular clinicopathological features and aggressive clinical behavior. Additional studies are needed to confirm these observations in larger series of patients.

Chromosome Aberrations↗
PubMed2004

Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities.

Plasmablastic lymphoma was initially described as a variant of diffuse large B-cell lymphoma (DLBCL) involving the oral cavity of HIV+ patients and characterized by immunoblastic morphology and a plasma cell phenotype. However, other lymphomas may exhibit similar morphologic and immunophenotypic features. To determine the significance of plasmablastic differentiation in DLBCL and examine the heterogeneity of lymphomas with these characteristics, we examined 50 DLBCLs with low/absent CD20/CD79a and an immunophenotype indicative of terminal B-cell differentiation (MUM1/CD38/CD138/EMA-positive). We were able to define several distinct subgroups. Twenty-three tumors were classified as plasmablastic lymphoma of the oral mucosa type and showed a monomorphic population of immunoblasts with no or minimal plasmacytic differentiation. Most patients were HIV+ and EBV was positive in 74%. Eleven (48%) cases presented in the oral mucosa, but the remaining presented in other extranodal (39%) or nodal (13%) sites. Sixteen cases were classified as plasmablastic lymphoma with plasmacytic differentiation. These were composed predominantly of immunoblasts and plasmablasts, but in addition exhibited more differentiation to mature plasma cells. Only 33% were HIV+, EBV was detected in 62%, and 44% had nodal presentation. Nine cases, morphologically indistinguishable from the previous group, were secondary extramedullary plasmablastic tumors occurring in patients with prior or synchronous plasma cell neoplasms, classified as multiple myeloma in 7 of the 9. Two additional neoplasms were an HHV-8+ extracavitary variant of primary effusion lymphoma and an ALK+ DLBCL. HHV-8 was examined in 39 additional cases, and was negative in all. In conclusion, DLBCLs with plasmablastic differentiation are a heterogeneous group of neoplasms with different clinicopathological characteristics that may correspond to different entities.

Adult↗
PubMed2002

Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma.

To analyze the relationship between immunophenotyping profile and main clinicopathological features and outcome in diffuse large B-cell lymphoma (DLBCL), we studied 128 patients (59 men, 69 women; median age 65 years) consecutively diagnosed with de novo DLBCL in a single institution. Cells from each patient were immunostained with CD20, CD79a, CD5, CD10, bcl-6, MUM1, CD138, bcl-2, p53, p27, and Ki-67 antibodies. Four immunophenotyping profiles were distinguished according to the pattern of differentiation: germinal center-CD10(+) (GC-CD10(+); CD10(+)/Bcl-6(+)/MUM1(-)/CD138(-)), germinal center-CD10(-) (GC-CD10(-); CD10(-)/Bcl-6(+)/ MUM1(-)/CD138(-)), post-germinal center (pGC; CD10(-)/bcl-6(+/-)/ MUM1(+)/CD138(-)), and plasmablastic (CD10(-)/bcl-6(-)/MUM1(+)/CD138(+)). Rearrangement of bcl-2 was studied by polymerase chain reaction (PCR) in 57 patients. Single-antigen expression was as follows: CD5, 2%; CD10, 21%; bcl-6, 72%; MUM1, 54%; CD138, 2%; bcl-2, 59%; p53, 28%; p27, 40%. Distribution according to differentiation profiles was as follows: GC-CD10(+), 24 patients, GC-CD10-, 30 patients; pGC, 60 patients; plasmablastic, 2 patients; other patterns, 12 patients. The pGC profile was associated with primary nodal presentation and immunoblastic morphology, whereas GC-CD10(+) tumors showed disseminated disease, centroblastic morphology, bcl-2 rearrangement, and lower Ki-67 proliferative index. GC-CD10(-) patients more often presented with primary extranodal origin, early stage, normal lactic acid dehydrogenase (LDH) levels, and low or low/intermediate International Prognostic Index (IPI) scores than the others. However, no significant difference was found in terms of response or overall survival (OS) according to these profiles. Expression of bcl-2 was associated with advanced stage, high or high-intermediate IPI, and poor OS. Expression of bcl-2 maintained predictive value in multivariate analysis, with stage and LDH. In conclusion, differentiation profile was associated with particular clinicopathological features but was not essential to predicting outcome in DLBCL patients.

Adult↗