Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome

Barrans, Sharon; Fenton, James A. L.; Banham, Alison H.; Owen, Roger G.; Jack, Andrew

doi:10.1182/blood-2004-03-1209

Cited by 202 publications

(171 citation statements)

References 16 publications

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“…It has been suggested that FOXP1 expression is an independent prognostic factor in diffuse large B-cell lymphoma patients. 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.…”

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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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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“…The prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in decisions regarding clinical treatment [26,27]. FOXP1 is targeted by recurrent chromosome translocations, and its overexpression confers a poor prognosis in numerous types of lymphomas [28][29][30][31][32], suggesting that it functions as an oncogene. However, FOXP1 localizes to a tumor suppressor locus at 3p14.1 [10], and loss of FOXP1 expression in breast cancer is associated with a worse outcome [12]; this suggests that FOXP1 functions as a tumor suppressor in other tissue types.…”

Section: Discussionmentioning

confidence: 99%

FOXP1, an Estrogen-Inducible Transcription Factor, Modulates Cell Proliferation in Breast Cancer Cells and 5-Year Recurrence-Free Survival of Patients with Tamoxifen-Treated Breast Cancer

et al. 2011

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Breast cancer is primarily a hormone-dependent tumor that can be regulated by the status of steroid hormones, including estrogen and progesterone. Forkhead box P1 (FOXP1) is a member of the forkhead box transcription factor family and has been reported to be associated with various types of tumors. In the present study, we investigated the expression of FOXP1 in 133 human invasive breast cancers, obtained by core biopsy, by immunohistochemical analysis. Nuclear immunoreactivity of FOXP1 was detected in 89 cases (67%) and correlated positively with tumor grade and hormone receptor status, including estrogen receptor alpha (ERα) and progesterone receptor, and negatively with pathological tumor size. In ERα-positive MCF-7 breast cancer cells, we demonstrated that FOXP1 mRNA was upregulated by estrogen and increased ERα recruitment to ER binding sites identified by ChIP-on-chip analysis within the FOXP1 gene region. We also demonstrated that proliferation of MCF-7 cells was increased by exogenously transfected FOXP1 and decreased by FOXP1-specific siRNA. Furthermore, FOXP1 enhanced estrogen response element-driven transcription in MCF-7 cells. Finally, FOXP1 immunoreactivity was sig-

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“…42 Uniform high expression of FoxP1 has been associated with a poor outcome. 45 Although we used a cut-point of 30% for FOXP1, we evaluated all cutpoints for significance using a survival tree method and none were significant. In addition, we specifically compared overall survival of those with 100% FOXP1 expression (28% of cases) to those with less than 100% FOXP1 expression.…”

Section: Discussionmentioning

confidence: 99%

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma

et al. 2005

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We sought to determine whether identification of poor-risk subgroups of diffuse large B-cell lymphoma (DLBCL) using immunohistochemical stains would have practical utility with regard to prognosis and therapeutic decisions. Tissue microarray blocks were created using replicate samples of formalin-fixed, paraffin-embedded tissue from 200 cases of de novo DLBCL. The sections were stained with antibodies to proteins that are expressed by activated or proliferating B cells including MUM1, FOXP1, bcl-2, survivin, protein kinase C-beta (PKC-b), cyclin D2, cyclin D3, and Ki-67. In univariate analysis, tumor expression of cyclin D2 (P ¼ 0.025) or PKC-b (P ¼ 0.015) was associated with a worse overall survival, whereas none of the other markers was predictive of overall survival. Patients with DLBCL that expressed either cyclin D2 or PKC-b had a 5-year overall survival of only 30% as compared to 52% for those who were negative for both markers (P ¼ 0.0019). In multivariate analysis, the expression of cyclin D2 or PKC-b was an independent predictor of poor overall survival (P ¼ 0.035). Cyclin D2 and PKC-b expression will be useful in designing a 'biological prognostic index' for patients with DLBCL.

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Strong expression of FOXP1 identifies a distinct subset of diffuse large B-cell lymphoma (DLBCL) patients with poor outcome

Cited by 202 publications

References 16 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

FOXP1, an Estrogen-Inducible Transcription Factor, Modulates Cell Proliferation in Breast Cancer Cells and 5-Year Recurrence-Free Survival of Patients with Tamoxifen-Treated Breast Cancer

Expression of PKC-beta or cyclin D2 predicts for inferior survival in diffuse large B-cell lymphoma

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