Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation

Natkunam, Yasodha; Lossos, Izidore S.; Taidi, Behnaz; Song, Zhao; Xiao, Lu; Ding, Feying; Hammer, Anne; Marafioti, Teresa; Byrne, Gerald E.; Levy, Shoshana; Warnke, Roger A.; Levy, Ronald

doi:10.1182/blood-2004-08-3112

Cited by 108 publications

(117 citation statements)

References 28 publications

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“…These results are in agreement with those recently published indicating that CDKN2A was deleted in 30% of ABC-DLBCL and only in 4% of GCB-DLBCL. 3 Interestingly, LMO2, often considered to be one of the most reliable GCB biomarkers, 31 is also among the most underexpressed genes in DLBCL 9p21del . Conversely, FUT8, which is included in the Wright classifier, is one of the most highly expressed genes in DLBCL 9p21del and ABC subtypes.…”

Section: Discussionmentioning

confidence: 99%

Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study

Jardin

Jaı̈s

Molina

et al. 2010

Blood

122

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Section: Discussionmentioning

confidence: 99%

Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study

Jardin

Jaı̈s

Molina

et al. 2010

Blood

122

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“…It has also been observed in a wide range (40 to 70%) of diffuse large B-cell lymphoma, with variable expression from strong reactivity in the majority of lymphoma cells to localized and even weak reactivity in a subset of the cells. 20,23,29 The Hans classifier 11 was one of the initially proposed algorithms with 87% of concordance with germinal expression profiling results; germinal center B subtype was defined as all cases expressing CD10 and cases that were CD10-negative, BCL6-positive, and MUM1-negative. All cases that were CD10-negative and MUM1-positive, irrespective of the BCL-6 result, were considered to be of nongerminal center-B-subtype origin.…”

Section: Discussionmentioning

confidence: 99%

“…16 HGAL (also know as GCET2) is a B-cell specific marker whose expression is observed in the cytoplasm of normal germinal center B-cells and in lymphomas of germinal center B-cell derivation, including subsets of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma, and Burkitt lymphoma. [19][20][21] In the current study, we incorporated HGAL/GCET2 to the three previously described algorithms across a cohort of 424 nodal diffuse large B-cell lymphoma cases. The aim of the study was to evaluate the potential utility of HGAL/GCET2 in recognizing cases of germinal center B-cell-type diffuse large B-cell lymphoma above and beyond those cases classified as germinal center B-cell-type diffuse large B-cell lymphoma using the three original algorithms.…”

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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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“…It was shown to be expressed in germinal center B lymphocytes and in lymphomas of germinal center derivation, such as Burkitt lymphoma, follicular lymphoma, nodular lymphocyte-predominant Hodgkin lymphoma, and diffuse large B-cell lymphomas. 10 The expression of HGAL is similar to CD10 and BCL6 in diffuse large B-cell lymphoma. However, its expression in primary cutaneous diffuse large B-cell lymphoma has not been studied.…”

mentioning

confidence: 87%

Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma

et al. 2008

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The classification of primary cutaneous large B-cell lymphoma (PCLBCL) is based on standard morphology, immunohistochemistry, and clinical presentation. There are two major subtypes in the current WHO-EORTC classification: follicle center lymphoma and diffuse large B-cell lymphoma, leg-type (DLBCL-LT). The goals of this study were to examine a series of DLBCLs to determine (1) whether the immunohistochemical paradigm of germinal center B-cell and non-germinal center B-cell types of systemic DLBCL could be applied to PCLBCL; (2) whether application of the newly described germinal center B-cell marker, human germinal center-associated lymphoma (HGAL) also discriminates between these types as a further support for germinal center B-cell origin for primary cutaneous center lymphoma; and (3) whether any of these biologic markers were of prognostic significance. To this end, 32 cases of diffuse PCLBCL (22 primary cutaneous follicular center lymphomas and 10 DLBCL-LT) were classified based on the WHO-EORTC criteria and studied for expression of CD20, BCL2, BCL6, CD10, MUM-1, and HGAL by immunohistochemistry. Results were correlated with clinical features. HGAL and BCL6 expression and germinal center B-cell phenotype were associated with primary cutaneous follicular center lymphoma. The combination of HGAL and BCL6 positivity had the highest sensitivity (88%) and specificity (100%) for predicting subtype compared to either marker alone. Both HGAL and BCL6 were associated with the germinal center B-cell phenotype. The correlation of HGAL expression with the germinal center B-cell phenotype demonstrates the role of this marker in the classification of cutaneous large B-cell lymphomas. BCL6 expression was the only immunohistochemical marker associated with overall survival. Characterizing PCLBCLs with markers of B-cell maturation stage is a useful framework for studying, classifying, and clinically stratifying these lymphomas.

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Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation

Cited by 108 publications

References 28 publications

Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study

Diffuse large B-cell lymphomas with CDKN2A deletion have a distinct gene expression signature and a poor prognosis under R-CHOP treatment: a GELA study

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

Expression of HGAL in primary cutaneous large B-cell lymphomas: evidence for germinal center derivation of primary cutaneous follicular lymphoma

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