Cyclin D1-negative Blastoid Mantle Cell Lymphoma Identified by SOX11 Expression
SOX11 expression has been recently shown to be useful in the diagnosis of mantle cell lymphoma (MCL), including cyclin D1-negative MCL with typical morphology. We evaluated SOX11 expression pattern in B-cell non-Hodgkin lymphoma (B-NHL) subtypes to confirm specificity and used it as a feature to identify the first reported cases of cyclin D1-negative blastoid MCL. SOX11 expression was evaluated by immunohistochemistry in 140 cases of mature B-NHL, including 4 cases of suspected blastoid MCL that lacked cyclin D1 expression and 8 cases of CD5-positive diffuse large B-cell lymphoma (DLBL). In addition, 5 cases of B or T lymphoblastic lymphoma were included. Nuclear expression of SOX11 was found in cyclin D1-positive MCL (30/30, 100%) and in a case of cyclin D1-negative MCL with typical morphology. SOX11 was also expressed in Burkitt lymphoma (1/5, 20%) and lymphoblastic lymphoma (2/3 T-LBLs, 2/2 B-LBLs, overall 4/5, 80%), whereas all cases of DLBL (including CD5 DLBL) and other small B-NHL were negative. The 4 suspected cases of blastoid MCL were also SOX11. These cases had a complex karyotype that included 12p abnormalities. We confirmed prior reports that stated that SOX11 nuclear expression was a specific marker for MCL, including cyclin D1-negative MCL with typical morphology. To our knowledge, this is the first report regarding its use in identifying cases of cyclin D1-negative blastoid MCL. Routine use of SOX11 in cases of suspected CD5 DLBL might help identify additional cases of cyclin D1-negative blastoid MCL.
Available from: Ying Qu
- "Immunohistochemistry (IHC) staining was performed using a highly sensitive streptavidin-biotin-peroxidase detection system with gastric cancer tissue microarrays. Mouse monoclonal anti-SOX11 at a dilution of 1:100 (Cell Marque, CA, USA) was used as previously reported (14). Mayer’s haematoxylin was used for counterstain. "
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ABSTRACT: SOX11 is involved in gastrulation and in malignant diseases. The aim of this study was to investigate the role of SOX11 in gastric cancer and its expression pattern and clinical significance. SOX11 overexpression cell model was used to examine in vitro and in vivo the role of SOX11 in cell growth and metastasis. Cell cycle analysis and Annexin V/PI double staining were used to investigate the effect of SOX11 on cell cycle progression and apoptosis. The expression of SOX11 in human gastric cancer was examined by immunohistochemistry. The correlation of SOX11 expression with clinicopathological characteristics and survival of patients was analyzed by Pearson's χ2 and Kaplan-Meier analyses, respectively. Cox's proportional hazard model was employed in multivariate analysis. SOX11 overexpression did not inhibit cell growth but strongly suppressed cell migration/invasion in vitro and in vivo. We found a significant correlation between high SOX11 protein levels and Lauren's classification (intestinal type), differentiation status (high and medium), and early TNM stage. SOX11 is an independent prognostic factor for improved survival in gastric cancer patients. SOX11 was a potential tumor-suppressor and an independent positive prognostic factor in gastric cancer patients with less advanced clinicopathological features.
Available from: Ulrika Andréasson
- "We show, using the monoclonal SOX11-C1 antibody, that 100% of the MCL cases (TMA) tested presented nuclear staining of SOX11, suggesting a disease-defining property. This is in accordance with recent reports, in which SOX11 also was shown to identify rare cases of cyclin D1-negative MCLs with either typical
 or blastoid
 morphology. However, the rare occurrence of SOX11 negative cases, was confirmed in a single MCL case, defined by 11;14 translocation and immunophenotyping. "
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The transcription factor SOX11 is of diagnostic and prognostic importance in mantle cell lymphoma (MCL) and epithelial ovarian cancer (EOC), respectively. Thus, there is an unmet clinical and experimental need for SOX11-targeting assays with low background, high specificity and robust performance in multiple applications, including immunohistochemistry (IHC-P) and flow cytometry, which until now has been lacking.
We have developed SOX11-C1, a monoclonal mouse antibody targeting SOX11, and successfully evaluated its performance in western blots (WB), IHC-P, fluorescence microscopy and flow cytometry.
We confirm the importance of SOX11 as a diagnostic antigen in MCL as 100% of tissue micro array (TMA) cases show bright nuclear staining, using the SOX11-C1 antibody in IHC-P. We also show that previous reports of weak SOX11 immunostaining in a fraction of hairy cell leukemias (HCL) are not confirmed using SOX11-C1, which is consistent with the lack of transcription. Thus, high sensitivity and improved specificity are demonstrated using the monoclonal SOX11-C1 antibody. Furthermore, we show for the first time that flow cytometry can be used to separate SOX11 positive and negative cell lines and primary tumors. Of note, SOX11-C1 shows no nonspecific binding to primary B or T cells in blood and thus, can be used for analysis of B and T cell lymphomas from complex clinical samples. Dilution experiments showed that low frequencies of malignant cells (~1%) are detectable above background using SOX11 as a discriminant antigen in flow cytometry.
The novel monoclonal SOX11-specific antibody offers high sensitivity and improved specificity in IHC-P based detection of MCL and its expanded use in flow cytometry analysis of blood and tissue samples may allow a convenient approach to early diagnosis and follow-up of MCL patients.
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ABSTRACT: This chapter provides information about immunohistochemical (IHC) studies used in diagnosing specific hematolymphoid neoplasms
in an up-to-date and easy-to-use format for the busy pathologist. It lists the most useful IHC markers of lymphoid and histiocytic/dendritic
neoplasms based on new WHO classification of tumors of hematopoietic and lymphoid tissue (2008). Most recent general information
about IHC markers used in hematopoietic neoplasms is listed in Table 1. When a lymph node biopsy is suspected to have a hematopoietic
neoplasm, the frequently used markers are presented in Table 2. Tables 3 to 5 illustrate the IHC markers used for the differential
diagnoses of mature B-cell lymphomas, mature T-cell lymphomas and lymphoid neoplasms with blastic morphology. IHC markers
helpful in lymphomas may also be expressed in non-hematopoietic neoplasms; these are explained in Table 6. Other tables focus
on the IHC markers used for specific lymphoid or histiocytic/dendritic neoplasms. We hope that this chapter will be useful
in diagnosing and the differential of hematopoietic neoplasms.
KeywordsB-cell lymphoma-T-cell lymphoma-NK-cell lymphoma-Histiocytic and dendritic cell neoplasm-Immunodeficiency-associated lymphoproliferative disorders
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