Pax-5 Expression in Nonhematopoietic Tissues

Torlakovic, Emina; Slipicevic, Ana; Robinson, Chris; DeCoteau, John F.; Alfsen, G. Cecilie; Vyberg, Mogens; Chibbar, Richa; Flørenes, Viví Ann

doi:10.1309/xec7-jmw9-yrm7-4rno

Cited by 48 publications

(28 citation statements)

References 26 publications

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“…The observed frequency of PAX5 staining in Merkel cell carcinoma in this series (3/17 cases, or 18%) is less than that previously reported by Dong et al 33 (29 of 31 cases) and Torlakovic et al 34 (two of two cases). PAX5 staining was not detected in seven additional neuroendocrine tumors from various sites.…”

Section: Pax5 In Undifferentiated Neoplasmscontrasting

confidence: 73%

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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Section: Pax5 In Undifferentiated Neoplasmscontrasting

confidence: 73%

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

et al. 2007

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“…However, differential regulation of p53 by PAX5, as reported in the literature, may result from cell or tissue specificity. Torlakovic et al (9) previously proposed that transcription factors exhibit their effect with regard to the environment they are expressed in, and therefore the interpretation of their effects requires prudence, in particular in a genetically unstable environment such as neoplasms. Such functional variability may also be the result of PAX5 alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

“…However, PAX5 expression is absent in terminally differentiated plasma cells (7). PAX5 mRNA expression has also been reported in the developing central nervous system and adult mouse testis (8) as well as in human adult brain tissue and some tissues of the male and female genital tract (9).…”

Section: Introductionmentioning

confidence: 99%

PAX5α Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells

Vidal

Perry

Vouyovitch

et al. 2010

Molecular Cancer Research

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Deregulated PAX5 expression has been associated with metastatic mammary carcinoma, although the precise role of PAX5 in cancer progression is unclear. Stable forced expression of PAX5α in the mammary carcinoma cell lines MCF-7 and MDA-MB-231 reduced cell cycle progression, cell survival, and anchorage-independent cell growth. In xenograft studies, forced expression of PAX5α was associated with a significant reduction in tumor volume. Furthermore, forced expression of PAX5α in mammary carcinoma cells resulted in altered cell morphology with resultant enhancement of epithelial cell characteristics. Morphologic changes were associated with localization of β-CATENIN at cell-cell junctions and with altered mRNA expression of mesenchymal markers in mammary carcinoma cells. In addition, forced expression of PAX5α in MCF-7 and MDA-MB-231 cells significantly reduced cell migration and invasion. Concomitantly, small interfering RNA-mediated depletion of PAX5α increased MCF-7 total cell number, cell motility, migration, and invasion. These studies show that PAX5α enhances the epithelial characteristics of mammary carcinoma cells, reminiscent of mesenchymal to epithelial transition. Mol Cancer Res; 8(3); 444-56. ©2010 AACR.

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“…Endocervical glands Not specified Not specified Not specified Not specified Multiple steps of genital tract development Not specified (Torlakovic et al, 2006) Hematopoietic System…”

Section: Pag Of Midbrain Medulla Oblongata Caudal Nucleus Smooth Muscmentioning

confidence: 99%

Perplexing Pax: From puzzle to paradigm

Blake

Thomas

Thompson

et al. 2008

Developmental Dynamics

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Pax transcription factors are critical for the development of the central nervous system (CNS) where they have a biphasic role, initially dictating CNS regionalization, while later orchestrating differentiation of specific cell subtypes. While a plethora of expression, misexpression, and mutation studies lend support for this argument and clarify the importance of Pax genes in CNS development, less well understood, and more perplexing, is the continued Pax expression in the adult CNS. In this article we explore the mechanism of action of Pax genes in general, and while being cognizant of existing developmental data, we also draw evidence from (1)

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Pax-5 Expression in Nonhematopoietic Tissues

Cited by 48 publications

References 26 publications

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

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

PAX5α Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells

Perplexing Pax: From puzzle to paradigm

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