Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Gutiérrez-García, Gonzalo; Cardesa-Salzmann, Teresa Marta; Climent, Fina; González‐Barca, Eva; Mercadal, Santiago; Mate, José Luís; Sancho, Juan Manuel; Arenillas, Leonor; Serrano, Sergi; Escoda, Lourdes; Martínez, Salomé; Valera, Alexandra; Martı́nez, Antonio; Jares, Pedro; Pinyol, Montserrat; García‐Herrera, Adriana; Martínez‐Trillos, Alejandra; Giné, Eva; Villamor, Neus; Campo, Elı́as; Colomo, Luís; López‐Guillermo, Armando

doi:10.1182/blood-2010-12-322362

Cited by 290 publications

(223 citation statements)

References 39 publications

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“…24 It proposed the use of the same three markers as Hans; however, the guidelines suggest that the cases that are negative for all germinal center markers and those that have one positive germinal center marker and expresses MUM1, should be designated unclassifiable cases. 27 In a series of 157 cases of diffuse large B-cell lymphoma studied by Gutierrez-Garcia et al, 29 the application of Colomo and Hans algorithms was similar-41% of germinal center B-subtype and 59% of non-germinal center B-subtype immunophenotype. In the same study using Choi and Tally's algorithms, the proportion of non-germinal center B subtype assigned was significantly higher-67% and 63% respectively.…”

Section: Discussionmentioning

confidence: 92%

“…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%

“…LMO2 expression in diffuse large B-cell lymphoma ranges in frequency from 40 to 55%. 23,29,30 In the current study, we introduced HGAL/GCET2 in addition to the other previously described markers. HGAL/ GCET2 protein is specifically expressed in lymphocytes within the germinal center in normal lymphoid tissue revealing cytoplasmic expression by immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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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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“…However, treatments still fail in 30-40% of patients, especially in the non-germinal center group. 4 Patients may benefit from novel strategies of targeted therapybased on the better understanding of diffuse large B-cell lymphoma.…”

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confidence: 99%

Activity and complexes of mTOR in diffuse large B-cell lymphomas—a tissue microarray study

et al. 2012

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Diffuse large B-cell lymphoma is a heterogeneous group of diseases with different responses to therapy. Targeting mTOR (mammalian target of rapamycin) offers a new approach to improve the treatment. mTOR inhibitors are being developed and are in clinical use in mantle cell lymphoma therapy and clinical trials are ongoing in other high-grade lymphomas as well. However, there is limited data about mTOR activity and the expression of its different complexes in diffuse large B-cell lymphomas. Tissue microarray blocks were constructed from paraffin-embedded biopsy specimens. More than 700 immunohistochemical stainings (mTOR signaling-related proteins and phosphoproteins, markers for lymphoma classification) were evaluated from 68 diffuse large B-cell lymphoma biopsies from conventionally treated and followed patients. Approximately 30% of cases were characterized as germinal center-derived diffuse large B-cell lymphomas, which showed virtually no mTOR activity, as determined by phospho-ribosomal S6 expression, the most sensitive marker of mTOR activity. In about 80% of non-germinal center-derived diffuse large B-cell lymphoma cases, positivity of mTOR-related phosphoproteins was observed, denoting mTOR activity. Moreover, Rictor (a characteristic protein of the mTOR complex2) was overexpressed in 43% of all diffuse large B-cell lymphomas and in 63% of mTOR-active nongerminal center diffuse large B-cell lymphoma samples. Rictor overexpression with mTOR activity indicated significantly worse survival for patients than mTOR inactivity or mTOR activity with low Rictor expression. These results suggest that mTOR activity is characteristic in most non-germinal center-derived diffuse large B-cell lymphomas with potentially variable mTOR-inhibitor sensitivity. Taken together, mTOR inhibitors may be useful in addition to regular therapy in diffuse large B-cell lymphomas, however, patient and inhibitor selection criteria must be carefully considered.

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Mature B‐ and T‐cell neoplasms and Hodgkin lymphoma

and

Aukema

2015

Cancer Cytogenetics

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Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Cited by 290 publications

References 39 publications

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

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

Activity and complexes of mTOR in diffuse large B-cell lymphomas—a tissue microarray study

Mature B‐ and T‐cell neoplasms and Hodgkin lymphoma

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