The B-Cell Transcription Factors BSAP, Oct-2, and BOB.1 and the Pan–B-Cell Markers CD20, CD22, and CD79a Are Useful in the Differential Diagnosis of Classic Hodgkin Lymphoma

Browne, Patrick; Petrosyan, Karen; Hernández, A.M.; Chan, Joel A.

doi:10.1309/ych8dwuffqbkgpvb

Cited by 104 publications

(85 citation statements)

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“…Similarly, OCT.1, OCT.2, and BOB.1 We did not find any significant association between OCT.1, OCT.2 and BOB.1 expression and the histological subtype, although the higher incidence of positivity of these markers in the lymphocyte-rich cases is notorious. This finding corroborates what previous studies have suggested about the fact that lymphocyte-rich classical Hodgkin's lymphoma might be more closely related to lymphocyte-predominant Hodgkin's lymphoma 30 than to the other classical subtypes or that it could be in between classical and lymphocyte-predominant Hodgkin's lymphoma. 33 From the 325 analysed cases, only a low percentage of them, less than expected, expressed CD20 and CD79a.…”

Section: Discussionsupporting

confidence: 92%

“…4,7,8,[28][29][30] In order to assess what previous studies have suggested about the lack of expression of transcription factors in classical Hodgkin's lymphoma, we performed an immunohistochemical analysis of OCT.1, OCT.2 and BOB.1 in 325 cases, using the tissue microarray technique and correlating the results to the histological subtype, B-cell marker expression, and Epstein-Barr virus presence. We decided to study the transcription factors on the neoplastic cells at Transcription factors in Hodgkin's lymphoma M García-Cosío et al the protein level because it might be more representative of their function than at the molecular level 28,31 and because there are few immunohistochemical studies including a large series of cases.…”

Section: Discussionmentioning

confidence: 99%

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Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

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Hodgkin's lymphoma can be considered in most cases a B-cell lymphoma due to the presence of potentially functional immunoglobulin (Ig) gene rearrangements in the neoplastic cells. In contrast to lymphocytepredominant Hodgkin's lymphoma, Hodgkin/Reed-Sternberg (HRS) cells from classical Hodgkin's lymphoma have low frequency of B-cell marker expression and lack Ig light and Ig heavy messenger RNA. Recent studies have shown transcription machinery deficiency in Hodgkin's lymphoma caused by an absence of the transcription factors OCT.1, OCT.2 and/or BOB.1. By using the tissue microarray technique, we have performed an immunohistochemical study of OCT.1, OCT.2 and BOB.1 in 325 classical Hodgkin's lymphoma cases. The results have been correlated with the expression of the B-cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the presence of Epstein-Barr virus and the histological subtype. The percentage of CD20 and CD79a positivity was low (18 and 18%, respectively), whereas MUM.1 and BSAP were positive in the majority of cases. Considering the positive cases with independence of the intensity of staining, 62% of them expressed OCT.2, 59% OCT.1 and 37% BOB.1. Nevertheless, when we considered only the strongly positive cases, the results were similar to those previously described by others. No statistical association was found between the transcription factor expression, histological subtype and Epstein-Barr virus presence. To our knowledge, this is the largest series of classical Hodgkin's lymphoma cases in which the expression of transcription factors has been studied. We have found a notorious percentage of cases displaying weak positivity for OCT.2 and BOB.1 factors in HRS cells. We propose that other mechanisms different from the absence of transcription factors OCT.2 and BOB.1 might be involved in the control of Ig transcription and B lineage in classical Hodgkin's lymphoma.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

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“…There is variation in the expression of these transcription factors reported in the literature due to small number of cases studied and/or to differences in immunohistochemical methods used. 9,10,22,23 We found a significant positive correlation between OCT.2 and CD79a expression (p=0.026), suggesting the existence of a common B-cell lineage down-regulating factor in H/RS cells. The latter observation was also made by Garcia-Cosio M et al 10 However, we did not find an association between BOB.1 and CD79a in our series.…”

Section: 1015mentioning

confidence: 63%

“…In the present study we analyzed the CD79a/ BCL6/MUM1 B-cell differentiation immunophenotypes and the B-cell transcription factors BOB.1/OCT.2 in H/RS cells in 107 cases of CHL aiming to elucidate the histogenesis of CHL and correlate the pattern of expression of these markers with clinical and laboratory characteristics and the patients' outcome. Most previous studies [8][9][10][11][12][13]22 have shown a variety of results regarding the expression of all these markers and furthermore their clinical significance is not clear.…”

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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“…Typically, CHL shows weaker PAX5 expression in Hodgkin cells than in background B lymphocytes. 7,25,26 Several researchers have described a drastic loss of the B-cell-specific gene expression program in Hodgkin/Reed-Sternberg cells that may be related to downregulation of PAX5 mRNA. 27,28 This downregulation of gene expression most likely corresponds at the phenotypic level to decreased PAX5 protein expression and to less intense staining in tissue biopsies.…”

Section: Pax5 In Undifferentiated Neoplasmsmentioning

confidence: 99%

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

et al. 2007

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PAX5 is a B-cell transcription factor whose expression at the protein level is reliably detected by immunohistochemistry in routine biopsies. The purpose of this study was to investigate whether PAX5 immunohistochemistry has diagnostic benefit as a B-cell marker in the work-up of undifferentiated malignant neoplasms. Twenty-five cases previously diagnosed as undifferentiated malignant neoplasms were selected. In addition, 59 hematolymphoid and 884 non-hematolymphoid malignancies were studied such that the specificity of PAX5 immunohistochemistry could be addressed. Two of the 25 (8%) undifferentiated neoplasms showed diffuse staining for PAX5, which indicated a B-cell derivation for these neoplasms that was not appreciated at the time of initial diagnosis. PAX5 staining was detected in the vast majority of hematolymphoid tumors of Bcell derivation but only in 5 of 884 (less than 1%) non-hematolymphoid tumors. Our results further show that PAX5 may be the only detectable marker of B lineage in lymphomas that lack or show equivocal CD45RB and CD20 expression. We conclude that the addition of PAX5 to a panel of immunohistologic markers used in the interrogation of undifferentiated neoplasms is of diagnostic benefit. Its expression can also facilitate the diagnosis of classical and nodular lymphocyte-predominant Hodgkin lymphoma with atypical morphologic and immunohistologic features. Lastly, we have shown that the lack of its expression at the protein level in many epithelial and mesenchymal neoplasms renders PAX5 expression an extremely specific marker of the B lineage. Keywords: PAX5; B cell; non-Hodgkin lymphoma; Hodgkin lymphoma; undifferentiated neoplasm PAX5 (B-cell-specific activator protein, BSAP) is a member of the paired box domain gene family that encodes nuclear transcription factors important in development, differentiation, cell migration and proliferation. 1,2 PAX5 protein is expressed as a nuclear marker in B-lineage cells that span the differentiation spectrum from precursor B cells to early plasma cells. 3,4 The expression of PAX5 protein is also a useful lineage-specific marker in hematopoietic neoplasms arising from B cells. [5][6][7][8] Staining for PAX5 has additional utility in the diagnosis of B-cell malignancies that lack expression of commonly used pan-B-cell markers such as CD20 and CD79a. 9 In addition to its expression in B cells, PAX5 protein and/or mRNA has been reported to be expressed in normal and neoplastic cell types in the central nervous system, testis and bladder. 3,[10][11][12][13][14][15] B-cell malignancies may express PAX5 in the absence of expression of other pan-B-cell markers, suggesting that the inclusion of PAX5 in a panel of antibodies to assess undifferentiated malignant neoplasms may have diagnostic benefit. To address this possibility, we studied examples previously diagnosed as undifferentiated malignant neoplasms for PAX5 expression by immunohistologic methods. Hodgkin and non-Hodgkin lymphomas (NHLs) that lacked or showed equivocal staining for CD20 were also i...

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The B-Cell Transcription Factors BSAP, Oct-2, and BOB.1 and the Pan–B-Cell Markers CD20, CD22, and CD79a Are Useful in the Differential Diagnosis of Classic Hodgkin Lymphoma

Cited by 104 publications

References 38 publications

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

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

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

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