SOX11: a potentially useful marker in surgical pathology: a systematic analysis of <scp>SOX</scp>11 expression in epithelial and non‐epithelial tumours

Xu, Sanpeng; Dong, Yuting; Huo, Zitian; Yu, Lu; Xue, Jing; Wang, Guoping; Duan, Yaqi

doi:10.1111/his.13757

Cited by 10 publications

(7 citation statements)

References 42 publications

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“…48 However, SOX11 expression has only been detected in 1 of 339 DLBCLs investigated in 5 previous studies. [49][50][51][52][53] Therefore, the very rare expression of SOX11 in DLBCL and the common expression of SOX11 in MCL together with the classic or blastoid MCL morphology, CD5 expression, and the aggressive clinical course in our cases favor the closer relationship of these CCNE 1 cases with MCL rather than DLBCL. Further studies are needed to confirm the most appropriate taxonomy of these uncommon cases.…”

Section: Discussionmentioning

confidence: 97%

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

Martín‐Garcia

Navarro

Valdés-Mas

et al. 2019

Blood

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Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation resulting in overexpression of cyclin D1. However, a small subset of cyclin D1− MCL has been recognized, and approximately one-half of them harbor CCND2 translocations while the primary event in cyclin D1−/D2− MCL remains elusive. To identify other potential mechanisms driving MCL pathogenesis, we investigated 56 cyclin D1−/SOX11+ MCL by fluorescence in situ hybridization (FISH), whole-genome/exome sequencing, and gene-expression and copy-number arrays. FISH with break-apart probes identified CCND2 rearrangements in 39 cases (70%) but not CCND3 rearrangements. We analyzed 3 of these negative cases by whole-genome/exome sequencing and identified IGK (n = 2) and IGL (n = 1) enhancer hijackings near CCND3 that were associated with cyclin D3 overexpression. By specific FISH probes, including the IGK enhancer region, we detected 10 additional cryptic IGK juxtapositions to CCND3 (6 cases) and CCND2 (4 cases) in MCL that overexpressed, respectively, these cyclins. A minor subset of 4 cyclin D1− MCL cases lacked cyclin D rearrangements and showed upregulation of CCNE1 and CCNE2. These cases had blastoid morphology, high genomic complexity, and CDKN2A and RB1 deletions. Both genomic and gene-expression profiles of cyclin D1− MCL cases were indistinguishable from cyclin D1+ MCL. In conclusion, virtually all cyclin D1− MCLs carry CCND2/CCND3 rearrangements with immunoglobulin genes, including a novel IGK/L enhancer hijacking mechanism. A subset of cyclin D1−/D2−/D3− MCL with aggressive features has cyclin E dysregulation. Specific FISH probes may allow the molecular identification and diagnosis of cyclin D1− MCL.

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Section: Discussionmentioning

confidence: 97%

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

Martín‐Garcia

Navarro

Valdés-Mas

et al. 2019

Blood

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“…A previous study found a significant expression of SOX11 in SCLC (68%) [ 19 ]. SOX11 appears to be a valuable diagnostic and prognostic marker for aggressive neuroendocrine tumors [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Expression and Clinicopathological Significance of SOX11 in Small-Cell Lung Cancer

Wang

Baoqi

et al. 2022

BioMed Research International

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Objective. This study aims to investigate the expression of neuronal transcription factor SOX11 in small-cell lung cancer (SCLC) and compare it with the expression of CD56 (nerve cell adhesion molecule), synaptophysin (Syn), chromogranin A (CgA), and thyroid transcription factor-1 (TTF-1) to explore the application value of SOX11 in the pathological diagnosis of SCLC. Methods. Immunohistochemical methods were used to detect the expression of SOX11, TTF-1, CD56, Syn, and CgA in 120 lung tumor tissues, and experimental results were analyzed using SPSS23.0 statistical software. Results. Immunohistochemical results showed that in the 120 lung tumor samples, SOX11 was highly expressed in SCLC and localized to the nucleus, with low or no expression in control carcinoid/lung neuroendocrine tumors, lung adenocarcinomas, and lung squamous cell carcinomas. Statistical analysis results revealed the following points. First, the expression of SOX11 was closely related to the tumor histological type. The expression of SOX11 in SCLC (positive rate of 63.33%) was significantly higher than that in carcinoid/neuroendocrine tumors (positive rate of 12.50%), lung adenocarcinoma (positive rate of 0%), and lung squamous cell carcinoma (positive rate of 0%). Second, immunohistochemical investigation of 60 SCLC cases revealed that the highest positive rates of CD56, TTF-1, and Syn, respectively, were 93.33 percent, 95 percent, and 86.67 percent. SOX11 also exhibited high sensitivity (0.633) and specificity (0.875) in SCLC. The positive rates of SOX11 and CgA were 63.33% and 50.00%, respectively. Statistical results revealed that the positive rate of CgA had no significant difference ( P > 0.05 ). Lastly, the combined use of antibodies SOX11, CgA, CD56, Syn, and TTF-1 was more beneficial to improving the diagnosis rate of SCLC than the single use of one or two antibodies. Conclusion. The expression of SOX11 in different histological types of lung tumors differs considerably. SOX11 is highly expressed in SCLC. SOX11 can be used as a beneficial supplement to the combination of classical neuroendocrine markers and in combination with CgA, CD56, Syn, and TTF-1 to assist in the diagnosis of SCLC.

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“…Thus, continued studies are needed to identify additional NE biomarkers. Our previous publication revealed that transcriptional factor SOX11 downstream of ASCL1 is expressed in high percentages of HG-NECs, particularly SCLCs [ 20 ]. In this study, we further compared SOX11 expression with other NE markers in different kinds of pulmonary carcinomas to access its diagnostic value, and found that SOX11 is a sensitive and more specific NE marker and can be a complement for diagnosis of HG-NECs.…”

Section: Discussionmentioning

confidence: 99%

“…One recent study revealed that SOX11 mRNA expression is significantly upregulated in SCLC and LCNEC and absent expression of SOX11 is correlated with prolonged survival [ 19 ]. In our recent publication we have already found that a high percentage of HG-NECs, particularly SCLCs, were immunopositive for SOX11 [ 20 ]. However, no extensive study comparing the expression of SOX11 with other common NE markers in pulmonary tumors has been reported so far.…”

Section: Introductionmentioning

confidence: 99%

SOX11 is a sensitive and specific marker for pulmonary high-grade neuroendocrine tumors

Dong

Xue

et al. 2022

Diagn Pathol

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Background Synaptophysin (SYN), chromogranin A (CGA), CD56 and insulinoma-associated protein 1 (INSM1) are proposed neuroendocrine (NE) markers used for diagnosis of pulmonary NE tumors. These NE markers have been identified in subsets of non-NE tumors requiring differential diagnosis, thus we sought to explore new NE markers. Methods We evaluated the immunohistochemical expression of SOX11, a transcription factor involved in neurogenesis, in pulmonary NE tumors and large cell carcinomas (LCCs). Results We found that SOX11 showed a sensitivity similar to INSM1 and CGA, and less than SYN and CD56 in small cell lung carcinomas (SCLCs) and large cell neuroendocrine carcinomas (LCNECs). While SOX11 is more specific than the other four markers for diagnosis of high-grade neuroendocrine carcinomas (HG-NECs) because 1) None of LCCs (0/63), the most challenging non-NE tumor type for differential diagnosis due to overlapped morphology with LCNECs displayed SOX11 positivity. While expression of at least one of SYN, CGA, CD56 or INSM1 was identified in approximately 60% (18/30) of LCCs. 2) SOX11 was only expressed in 1 of 37 carcinoid tumors in contrast to diffuse expression of SYN, CGA, CD56 and INSM1. In HG-NECs, we noticed that SOX11 was a good complementary marker for SCLC diagnosis as it was positive in 7 of 18 SYN−/CGA−/CD56− SCLCs and 3 of 8 SYN−/CGA−/CD56−/INSM1− SCLCs, and SOX11 positivity in 4 of 6 SYN−/CGA−/CD56− cases previously diagnosed as LCCs with NE morphology provides additional evidence of NE differentiation for reclassification into LCNECs, which was further confirmed by electromicroscopical identification of neurosecretory granules. We also found SOX11 expression cannot predict the prognosis in patients with HG-NECs. Conclusions Therefore, SOX11 is a useful complementary transcriptional NE marker for diagnosis and differential diagnosis of SCLC and LCNEC.

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SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non‐epithelial tumours

Abstract: SOX11 showed prominent expression in neuroectodermal tumours with neural differentiation, high grade-NEC, SDC, rhabdomyosarcoma and MRCL. The high sensitivity and specificity of SOX11 in SDC and MRCL make it a useful diagnostic marker.

Cited by 10 publications

References 42 publications

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

CCND2 and CCND3 hijack immunoglobulin light-chain enhancers in cyclin D1− mantle cell lymphoma

Expression and Clinicopathological Significance of SOX11 in Small-Cell Lung Cancer

SOX11 is a sensitive and specific marker for pulmonary high-grade neuroendocrine tumors

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