Influence of Biologic Markers on the Outcome of Hodgkin's Lymphoma: A Study by the Spanish Hodgkin’s Lymphoma Study Group

Montalbán, Carlos; Garcı́a, Juan F.; Abraira, Víctor; González-Camacho, Leocricia; Morente, Manuel; Bello, J.; Conde, Eulogio; Crúz, Miguel A.; García‐Sanz, Ramón; García-Laraña, José; Grande, Carlos; Llanos, Marta; Martínez, Rafael Martínez; Flores, Eduardo; Méndez, Miguel; Ponderós, Concepción; Rayón, Consolación; Sánchez-Godoy, Pedro; Zamora, Javier; Piris, Miguel Á.

doi:10.1200/jco.2004.06.105

Cited by 61 publications

(78 citation statements)

References 49 publications

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“…Several studies have attempted to identify biological parameters that could be helpful in the prognostic evaluation of patients at initial diagnosis and in planning treatment. 3,4 The aims of the present study were to clarify the histogenetic origin of H/RS cells in CHL and identify subgroups with different clinical characteristics and prognoses.…”

mentioning

confidence: 99%

A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4

Valsami¹,

Pappa²,

Rontogianni³

et al. 2007

Haematologica

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confidence: 99%

A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4

Valsami¹,

Pappa²,

Rontogianni³

et al. 2007

Haematologica

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“…[7][8][9][10][11][12] Methods previously employed in the identification of biomarkers have included enzyme-linked immunosorbent assays, immunohistochemistry of tissue microarrays, immunoradiometric assays, reverse transcriptase-polymerase chain reaction, gene and protein expression profiling and mass spectrometry-based methods. [13][14][15] To date, the identification of biomarkers in HL has been limited to known proteins for which there exist antibodies.…”

mentioning

confidence: 99%

Comprehensive identification of proteins in Hodgkin lymphoma-derived Reed–Sternberg cells by LC-MS/MS

Wallentine

Kim

Seiler

et al. 2007

Laboratory Investigation

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Mass spectrometry-based proteomics in conjunction with liquid chromatography and bioinformatics analysis provides a highly sensitive and high-throughput approach for the identification of proteins. Hodgkin lymphoma is a form of malignant lymphoma characterized by the proliferation of Reed-Sternberg cells and background reactive lymphocytes. Comprehensive analysis of proteins expressed and released by Reed-Sternberg cells would assist in the discovery of potential biomarkers and improve our understanding of its pathogenesis. The subcellular proteome of the three cellular compartments from L428 and KMH2 Hodgkin lymphoma-derived cell lines were fractionated, and analyzed by reversephase liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Additionally, proteins released by Hodgkin lymphoma-derived L428 cells were extracted from serum-free culture media and analyzed. Peptide spectra were analyzed using TurboSEQUEST s against the UniProt protein database (5.26.05; 188 712 entries). A subset of the identified proteins was validated by Western blot analysis, immunofluorescence microscopy and immunohistochemistry. A total of 1945 proteins were identified with 785 from the cytosolic fraction, 305 from the membrane fraction, 441 from the nuclear fraction and 414 released proteins using a minimum of two peptide identifications per protein and an error rate of o5.0%. Identification of proteins from diverse functional groups reflected the functional complexity of the Reed-Sternberg proteome. Proteins with previously reported oncogenic function in other cancers and from signaling pathways implicated in Hodgkin lymphoma were identified. Selected proteins without previously demonstrated expression in Hodgkin lymphoma were validated by Western blot analysis (B-RAF, Erb-B3), immunofluorescence microscopy (Axin1, Tenascin-X, Mucin-2) and immunohistochemistry using a tissue microarray (BRAF, PIM1). This study represents the first comprehensive inventory of proteins expressed by Reed-Sternberg cells of Hodgkin lymphoma and demonstrates the utility of combining cellular subfractionation, protein precipitation, tandem mass spectrometry and bioinformatics analysis for comprehensive identification of proteins that may represent potential biomarkers of the disease.

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“…These data have also been reported as negative prognostic factors for survival in HD. 24,32,34,39 The present study was a retrospective analysis, but these findings have led us to attempt to be more specific regarding prognostic factors in this disease. 38 The treatment for HD changed over the admission period for these patients, but the ratios of first CR and OS remained almost the same, because of the high sensitivity of the tumor to chemotherapy.…”

Section: Resultsmentioning

confidence: 99%

“…These data show that, if a larger sample were used, a signifi cant result might be found, as observed by other authors. [17][18][19][33][34][35]39 B symptoms and WBC counts higher than 10x10 9 /µl were unfavorable independent factors for achieving the first CR. Bone marrow tumor infiltration, B symptoms and hemoglobin levels less than 12 g/dl had a negative influence on OS.…”

Section: Resultsmentioning

confidence: 99%

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin’s disease

et al. 2007

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CONTEXT AND OBJECTIVE: Tumor cells in Hodgkin’s disease (HD) express cell proliferation markers that are evaluated according to the oncogenes involved or the expression of their proteins. Correlations between the protein expression grade and clinical data are now important for disease prognosis. DESIGN AND SETTING: This was a retrospective analysis on proliferating cell nuclear antigen (PCNA), p53 and MDM2 (murine double minute-2) expression using immunohistochemistry, on formalin-fixed, paraffin-embedded tissues from diagnostic biopsies on 51 patients with HD. The study was conducted at the Division of Hematology and Transfusion Medicine, Hospital São Paulo, Universidade Federal de São Paulo. METHODS: Antigen expression was evaluated as the proportions of positive Hodgkin and Reed-Sternberg (HRS) cells and reactive lymphocytes (L), which were compared using Spearman correlation coefficients. The Friedman test was used for comparisons between the markers. The Pearson test was used to investigate associations between marker expression and clinical and laboratory parameters, marrow involvement, complete remission (CR) and overall survival (OS) rates. RESULTS: There was overexpression of antigen proteins in HRS, in relation to L (p < 0.001). In HRS, MDM2 was higher than p53 and PCNA (p < 0.003), while the latter two were equivalent. In L, p53 was lower than MDM2 and PCNA (p < 0.001), while the latter two were equivalent. There was no relationship between protein expression and clinical and laboratory variables or outcome. CONCLUSIONS: PCNA, p53 and MDM2 are tumor markers for HD, but showed no clinical or prognostic significance in our analysis.

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Influence of Biologic Markers on the Outcome of Hodgkin's Lymphoma: A Study by the Spanish Hodgkin’s Lymphoma Study Group

Abstract: The data from this exploratory study suggest that the accumulation of molecular events seems to influence the outcome of HL, particularly in the low-IPS group.

Cited by 61 publications

References 49 publications

A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4

A clinicopathological study of B-cell differentiation markers and transcription factors in classical Hodgkin's lymphoma: a potential prognostic role of MUM1/IRF4

Comprehensive identification of proteins in Hodgkin lymphoma-derived Reed–Sternberg cells by LC-MS/MS

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkin’s disease

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