Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas

Montes‐Moreno, Santiago; Roncador, Giovanna; Maestre, Lorena; Martínez, Nerea; Sánchez-Verde, Lydia; Camacho, Francisca I.; Cannata, Jimena; Martı́nez-Torrecuadrada, Jorge L.; Shen, Yulei; Chan, Wing C.; Piris, Miguel Á.

doi:10.1182/blood-2007-06-094151

Cited by 72 publications

(57 citation statements)

References 29 publications

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“…KLHL6 is a BTB-kelch protein involved in germinal-center B-cell maturation, 10 whereas GCET1 (germinal-center B cell-expressed transcript-1) is thought to be expressed exclusively by neoplasms that arrested at the germinal-center stage of differentiation. 11 These markers were positive in most of the nodular lymphocyte-predominant Hodgkin's lymphoma cases, which is evidence of a germinal-center stage of differentiation in lymphocytic and/or histiocytic Reed-Sternberg cell variants. 12 Interestingly, mononuclear Hodgkin's cells and multinucleated ReedSternberg cells in lymphocyte-rich classical Hodgkin's lymphoma commonly express KLHL6 (69%, 11 of 16), a molecule that has been implicated in BCR signal transduction and in the formation of the full germinal-center response.…”

Section: Discussionmentioning

confidence: 80%

Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers

et al. 2009

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The existence, diagnostic features, and the biological and clinical relevance of lymphocyte-rich classical Hodgkin's lymphoma remain controversial. A comparative marker analysis of lymphocyte-rich classical Hodgkin's lymphoma, nodular lymphocyte-predominance Hodgkin's lymphoma, and of other subtypes of classical Hodgkin's lymphoma was carried out. Markers were selected focusing on B-cell lineage and transcription program (OCT.1, OCT.2, BOB.1, BCL6, PAX-5, GCET1, KLHL6, and BLIMP1), the NF-jB signaling pathway (REL-B, C-REL, TRAF-1, p-50, and MUM-1) and the T-cell microenvironment (CD3, CD57, PD-1, CXCL-13, and CD10, BCL-6, CD23). Lymphocyte-rich classical Hodgkin's lymphoma cases displayed features intermediate between those of classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma. The expression of B-cell transcription factors such as OCT.1, OCT.2, BOB.1, and BCL6 was more frequent in lymphocyte-rich classical Hodgkin's lymphoma than in classical Hodgkin's lymphoma. A follicular T-cell microenvironment was also identified in 50% of lymphocyte-rich classical Hodgkin's lymphoma cases. NF-kB markers were expressed at frequencies comparable with those observed in classical Hodgkin's lymphoma. The neoplastic cell immunophenotype and microenvironment in lymphocyte-rich classical Hodgkin's lymphoma closely mimic that which are observed in the outer zone of the germinal center, where B-cell blasts with germinal-center markers co-express CD30 and the B-cell transcription program, surrounded by follicular T-cell rosettes. Lymphocyte-rich classical Hodgkin's lymphoma seems to be characterized by a stronger expression of the B-cell transcription program by the neoplastic cells and by a follicular T-cell background, occupying an intermediate position between classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma.

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Section: Discussionmentioning

confidence: 80%

Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers

et al. 2009

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“…25,26 GCET-1 is highly restricted to germinal center B-cell and to germinal center B cell-derived cell lines and lymphomas. 27,28 Its expression has been observed in variable proportions of diffuse large B-cell lymphoma (20-50%) in different studies, most likely due to differences in scoring criteria. 28,29 In addition, we also assessed the expression of LMO2, which was incorporated into the Tally algorithm.…”

Section: Discussionmentioning

confidence: 99%

“…27,28 Its expression has been observed in variable proportions of diffuse large B-cell lymphoma (20-50%) in different studies, most likely due to differences in scoring criteria. 28,29 In addition, we also assessed the expression of LMO2, which was incorporated into the Tally algorithm. LMO2 expression in diffuse large B-cell lymphoma ranges in frequency from 40 to 55%.…”

Section: Discussionmentioning

confidence: 99%

The contribution of HGAL/GCET2 in immunohistological algorithms: a comparative study in 424 cases of nodal diffuse large B-cell lymphoma

et al. 2012

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Diffuse large B-cell lymphoma can be subclassified into at least two molecular subgroups by gene expression profiling: germinal center B-cell like and activated B-cell like diffuse large B-cell lymphoma. Several immunohistological algorithms have been proposed as surrogates to gene expression profiling at the level of protein expression, but their reliability has been an issue of controversy. Furthermore, the proportion of misclassified cases of germinal center B-cell subgroup by immunohistochemistry, in all reported algorithms, is higher compared with germinal center B-cell cases defined by gene expression profiling. We analyzed 424 cases of nodal diffuse large B-cell lymphoma with the panel of markers included in the three previously described algorithms: Hans, Choi, and Tally. To test whether the sensitivity of detecting germinal center B-cell cases could be improved, the germinal center B-cell marker HGAL/GCET2 was also added to all three algorithms. Our results show that the inclusion of HGAL/GCET2 significantly increased the detection of germinal center B-cell cases in all three algorithms (Po0.001). The proportions of germinal center B-cell cases in the original algorithms were 27%, 34%, and 19% for Hans, Choi, and Tally, respectively. In the modified algorithms, with the inclusion of HGAL/GCET2, the frequencies of germinal center B-cell cases were increased to 38%, 48%, and 35%, respectively. Therefore, HGAL/GCET2 protein expression may function as a marker for germinal center B-cell type diffuse large B-cell lymphoma. Consideration should be given to the inclusion of HGAL/GCET2 analysis in algorithms to better predict the cell of origin. These findings bear further validation, from comparison to gene expression profiles and from clinical/therapeutic data.

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“…Several studies have shown that these newer markers are also positive in the majority of cases of FL (470% for LMO2 and 490% for HGAL and GCET1) [14][15][16][17] . In routine practice, the diagnosis of FL can typically be established using CD10 and BCL6 as GC markers, but these newer GC-associated markers may also be helpful in selected cases, such as CD10-negative FL.…”

Section: Follicular Lymphomamentioning

confidence: 99%

Nodal and leukemic small B-cell neoplasms

Cook

2013

Modern Pathology

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The small B-cell neoplasms represent some of the most frequently encountered lymphoproliferative disorders in routine surgical pathology practice. This report reviews the current diagnostic criteria for classifying small B-cell neoplasms and distinguishing them from newly recognized precursor conditions that do not appear to represent overt lymphomas. Newly available immunohistochemical stains and molecular studies that may assist in the diagnosis and classification of these neoplasms are also discussed.

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Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas

Cited by 72 publications

References 29 publications

Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers

Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers

The contribution of HGAL/GCET2 in immunohistological algorithms: a comparative study in 424 cases of nodal diffuse large B-cell lymphoma

Nodal and leukemic small B-cell neoplasms

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