Pax-5 immunoexpression in various types of benign and malignant tumours: a high-throughput tissue microarray analysis

Mhawech‐Fauceglia, Paulette; Saxena, Rhakee; Zhang, Shaozeng; Terracciano, Luigi; Sauter, Guido; Chadhuri, Arundhuti; Herrmann, Françoís; Penetrante, Remedios

doi:10.1136/jcp.2006.039917

Cited by 71 publications

(73 citation statements)

References 21 publications

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“…This is supported by expression data from the gene expression database Oncomine, which indicated that PAX5 expression is positively correlated with breast cancer metastasis in three studies (28,30,31). In contrast, an immunohistochemical study conducted by MhawechFauceglia et al (52) detected PAX5 in only one case out of 164 benign and malignant tumor samples. However, Mhawech-Fauceglia et al also failed to observe expression of PAX5 in cases of astrocytomas, medulloblastomas, and neuroblastomas, whereas several other studies have shown expression of PAX5 mRNA in these three pathologies (14)(15)(16).…”

Section: Discussionmentioning

confidence: 61%

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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Section: Discussionmentioning

confidence: 61%

PAX5α Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells

Vidal

Perry

Vouyovitch

et al. 2010

Molecular Cancer Research

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“…Previous studies have identified that the PAX5 gene, which is located on chromosome 19p13 (Stapleton et al, 1993;Kovac et al, 2000), is associated frequently with chromosomal translocations (Busslinger et al, 1996). Aberrant PAX5 expression has been reported in several tumors (Baumann Kubetzko et al, 2004;Meza et al, 2006;Mhawech-Fauceglia et al, 2007;Lazzi et al, 2009), thus dysregulated expression of PAX5 is likely to be involved in carcinogenesis and the malignant progression of human cancers. A recent study demonstrated that the lack of expression of PAX5 in lymphoid neoplasms is associated with promoter hypermethylation, and cases with PAX5 silence were characterized by poor clinical outcome (Lazzi et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic inactivation of paired box gene 5, a novel tumor suppressor gene, through direct upregulation of p53 is associated with prognosis in gastric cancer patients

Cheung

et al. 2011

Oncogene

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Using genome-wide methylation screening, we identified that paired box gene 5 (PAX5) is involved in human cancer development. However, the function of PAX5 in gastric cancer (GC) development is largely unclear. We analyzed its epigenetic inactivation, biological functions and clinical application in GC. PAX5 was silenced in seven out of eight GC cell lines. A significant downregulation was also detected in paired gastric tumors compared with adjacent non-cancerous tissues. The downregulation of PAX5 was closely linked to the promoter hypermethylation status and could be restored with demethylation treatment. Ectopic expression of PAX5 in silenced GC cell lines (AGS and BGC823) inhibited colony formation and cell viability, arrested cell cycle, induced apoptosis, suppressed cell migration and invasion and repressed tumorigenicity in nude mice. Consistent with the induction of apoptosis by PAX5 in vitro, terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) staining showed significantly enhanced apoptotic cells in PAX5-expressed tumors compared with the vector control tumors. On the other hand, knockdown of PAX5 by PAX5-short hairpin RNA increased the cell viability and proliferation. The antitumorigenic function of PAX5 was revealed to be mediated by upregulating downstream targets of tumor protein 53 (p53), p21, BCL2-associated X protein, metastasis suppressor 1 and tissue inhibitors of metalloproteinase 1, and downregulating BCL2, cyclin D1, mesenchymal-epithelial transition factor (MET) and matrix metalloproteinase 1. Immunoprecipitation assay demonstrated that PAX5 directly bound to the promoters of p53 and MET. Moreover, PAX5 hypermethylation was detected in 77% (144 of 187) of primary GCs compared with 10.5% (2/19) of normal gastric tissues (Po0.0001).GC patients with PAX5 methylation had a significant poor survival compared with the unmethylated cases as demonstrated by Cox regression model and log-rank test.In conclusion, PAX5 is a novel functional tumor suppressor in gastric carcinogenesis. Detection of methylated PAX5 can be utilized as an independent prognostic factor in GC.

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“…Eventually 763 cases of cutaneous Merkel cell carcinoma were retrieved from the English literature and included in our review. 15,[18][19][20][21][22][23][24][25][26][27][28][29] …”

Section: Case Selectionmentioning

confidence: 99%

“…We also studied expression of PAX5 and TdT in our cases; both markers have been detected in the majority of cutaneous Merkel cell carcinomas. [18][19][20][21][22] …”

mentioning

confidence: 99%

Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart

Pan

Chen

et al. 2014

Modern Pathology

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Rare cases of Merkel cell carcinoma have been encountered in lymph nodes with unknown extranodal primary, which exhibit similar morphologic and immunophenotypic features to those in primary cutaneous Merkel cell carcinomas. However, it is uncertain whether the nodal Merkel cell carcinoma is a primary tumor of the lymph node or represents a metastasis from an occult or regressed extranodal lesion. To establish an accurate diagnosis of the nodal Merkel cell carcinoma can be challenging because of significant morphologic mimics, including lymphoblastic lymphoma and metastatic small cell carcinoma. Moreover, there is no consensus for a diagnostic term, and many different terms have been used, which can be confusing and may not fully reflect the nature of nodal Merkel cell carcinoma. In this study, we investigated the detailed clinicopathologic features of 22 nodal Merkel cell carcinomas, with comparison to 763 primary cutaneous cases retrieved from the literature. Overall, the nodal and cutaneous Merkel cell carcinomas shared similar clinical presentations, morphologic spectrum, and immunophenotype; both were mostly seen in elderly male with a typical neuroendocrine morphology. Most of cases expressed CK20, synaptophysin, and chromogranin A; and PAX5 and TdT were also positive in majority of cases. However, nodal Merkel cell carcinomas had a significantly lower association with Merkel cell polyomavirus than cutaneous cases (31% vs 76%, P ¼ 0.001). Therefore, these two entities may arise from overlapping but not identical biological pathways. We also recommend the use of the diagnostic term 'Merkel cell carcinoma of lymph node' to replace many other names used.

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Pax-5 immunoexpression in various types of benign and malignant tumours: a high-throughput tissue microarray analysis

Abstract: Despite its expression in a small subset of malignancies of epithelial origin, Pax-5 is still a good and reliable immunomarker in diagnosing B-NHL, HL and neuroendocrine carcinomas.

Cited by 71 publications

References 21 publications

PAX5α Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells

PAX5α Enhances the Epithelial Behavior of Human Mammary Carcinoma Cells

Epigenetic inactivation of paired box gene 5, a novel tumor suppressor gene, through direct upregulation of p53 is associated with prognosis in gastric cancer patients

Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart

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