The importance of the decline of BSAP levels in the germinal center B cells remains to be determined. Finally, the absence of BSAP in immunoblasts and plasma cells is consistent with its known downregulation in Ig-secreting cells. The neoplastic B cells also displayed varying levels of BSAP that to some extent paralleled the levels found in the corresponding normal cells.
Strong BSAP expression was observed in mantle cell lymphomas. This may reflect the derivation of this lymphoma from the strongly positive mantle zone B cells. Whether the high level of BSAP in these tumors contributes to their unfavorable clinical course in comparison with other low grade lymphomas remains to be determined.
Weaker immunoreactivity of prolymphocytes and paraimmunoblasts than of small lymphoma cells was a characteristic finding. In some cases, BSAP immunoreactivity even spared the proliferation centers. Because prolymphocytes and paraimmunoblasts have a higher proliferative activity compared with the surrounding tumor cells, 42 their lower BSAP levels contrasts with the positive correlation between BSAP levels and B-cell proliferation.
In many cases, these levels approximated the high levels seen in normal mantle cells, in contrast to the low to moderate levels seen in their corresponding nonneoplastic counterpart, reactive follicle center B cells. In contrast to follicular lymphoma, the majority of monocytoid B cells in toxoplasma lymphadenitis, as well as in tumor cells of marginal zone lymphomas composed of monocytoid cells , displayed no or low levels of BSAP expression.
Among lymphomas, this phenomenon was most apparent in primary monocytoid B-cell MALT-type lymphomas of the parotid gland. Monocytoid and marginal zone B cells are considered to be memory B cells. We did not find nuclear BSAP expression in either normal or neoplastic plasma cells. Consistent with our results, a recent study on PAX-5 mRNA expression in human multiple myeloma cell lines and primary myeloma cells also reported the failure to detect PAX-5 expression in these cells. Most LBCLs are thought to arise from peripheral antigen stimulated B cells; however, the clinical, pathological, and molecular heterogeneity of these lymphomas suggests their derivation from B cells of various stages of differentiation, and this heterogeneity was reflected in their BSAP expression.
The strong BSAP expression may be part of their malignant phenotype, representing overexpression of the protein. The nonrandom chromosomal translocation t 9;14 p13;q32 has been reported in cases of the lymphoplasmacytoid lymphoma subtype of NHL.
Lymphoplasmacytoid lymphomas are relatively rare; in the current study, none was included. BSAP was detected in cell lines corresponding to precursor and mature B-cell stages, but not in terminally differentiated plasma cell, T-cell, or other hematopoietic cell lines Table 2 and Fig 3. A similar, although less prominent band was also found in lysates from the pre-B—cell line Nalm Distinct Pax-5 isoforms generated by alternative splicing have been described in murine neural, B-lymphoid, and testicular tissues.
The strong expression of PAX-5 found in B-cell lymphomas may possibly indicate a role for this paired box protein in some lymphomas. On the other hand, because BSAP is strongly expressed normally during some stages of normal B-cell differentiation eg, mantle cells , we can only infer involvement of BSAP in those lymphomas for which the intensity of expression exceeded the expression level of the putative normal cellular counterpart deregulated expression.
We conclude that BSAP expression is unique to the B-cell lineage among hematopoietic cells and tumors. BSAP levels vary among B-cell subsets and among subtypes of B-cell lymphoma, with the highest levels detected in normal and neoplastic mantle cells, in some FLs, and in a proportion of LBCL, including all mediastinal large B-cell lymphomas studied.
We also thank Cynthia A. Harris and Sarah E. Delay-Brown for their expert technical assistance and Ralph L.
Isenberg for his photographic assistance. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" is accordance with 18 U. Sign In or Create an Account. Sign In. Skip Nav Destination Content Menu. Close Abstract. Article Navigation.
This Site. Google Scholar. Andreas W. Himmelmann , Andreas W. Thierry Fest , Thierry Fest. Agostino Riva , Agostino Riva. Axel Wellmann , Axel Wellmann. Eniko Bagdi , Eniko Bagdi. John H. Kehrl , John H. Elaine S. Jaffe , Elaine S. Mark Raffeld Mark Raffeld.
Blood 92 4 : — Article history Submitted:. Cite Icon Cite. This is a US government work. There are no restrictions on its use. View large Download PPT. Table 1. BSAP Positivity. Overall Positivity. F Focal nucleolar staining.
View Large. Table 2. Cell Line. BSAP Expression. Supported in part by a grant from the Swiss National Foundation to A. A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. Search ADS. Properties of B cell stage specific and ubiquitous nuclear factors binding to immunoglobulin heavy chain gene switch regions.
LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer. PAX-genes expression during human embryonic development, a preliminary report. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Structural characterization of the FKHR gene and its rearrangement in alveolar rhabdomyosarcoma.
Expression of Pax-2 in human renal cell carcinoma and growth inhibition by antisense oligonucleotides. Mechanism for transcriptional gain of function resulting from chromosomal translocation in alveolar rhabdomyosarcoma. Pax5 expression correlates with increasing malignancy in human astrocytomas. The t 9;14 p13;q32 chromosomal translocation associated with lymphoplasmocytoid lymphoma involves the PAX-5 gene.
Loss of tumor marker-immunostaining intensity on stored paraffin slides of breast cancer. B cell differentiation and isotype switching is related to division cycle number.
We have also observed nuclear reactivity in splenic endothelial cells and histiocytes, and we have seen cytoplasmic reactivity with PAX-5 in basal layers of the epidermis as well as in metaplastic respiratory epithelium. PAX-5 is a pan-B-cell marker that is very useful in the evaluation of lymphoid lesions, particularly in small biopsies and in cases where CD20 is negative. Although unusual in epithelial malignancies, PAX-5 is expressed in a subset of neuroendocrine carcinomas.
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