TrkC signaling is activated in adenoid cystic carcinoma and requires NT-3 to stimulate invasive behavior.
Oncogene
Treatment options for adenoid cystic carcinoma (ACC) of the salivary gland, a slowly growing tumor with propensity for neuroinvasion and late recurrence, are limited to surgery and radiotherapy. Based on expression analysis performed on clinical specimens of salivary cancers, we identified in ACC expression of the neurotrophin-3 receptor TrkC/NTRK3, neural crest marker SOX10, and other neurologic genes. Here, we characterize TrkC as a novel ACC marker, which was highly expressed in 17 out of 18 ACC primary-tumor specimens, but not in mucoepidermoid salivary carcinomas or head and neck squamous cell carcinoma. Expression of the TrkC ligand NT-3 and Tyr-phosphorylation of TrkC detected in our study suggested the existence of an autocrine signaling loop in ACC with potential therapeutic significance. NT-3 stimulation of U2OS cells with ectopic TrkC expression triggered TrkC phosphorylation and resulted in Ras, Erk 1/2 and Akt activation, as well as VEGFR1 phosphorylation. Without NT-3, TrkC remained unphosphorylated, stimulated accumulation of phospho-p53 and had opposite effects on p-Akt and p-Erk 1/2. NT-3 promoted motility, migration, invasion, soft-agar colony growth and cytoskeleton restructuring in TrkC-expressing U2OS cells. Immunohistochemical analysis demonstrated that TrkC-positive ACC specimens also show high expression of Bcl2, a Trk target regulated via Erk 1/2, in agreement with activation of the TrkC pathway in real tumors. In normal salivary gland tissue, both TrkC and Bcl2 were expressed in myoepithelial cells, suggesting a principal role for this cell lineage in the ACC origin and progression. Sub-micromolar concentrations of a novel potent Trk inhibitor AZD7451 completely blocked TrkC activation and associated tumorigenic behaviors. Pre-clinical studies on ACC tumors engrafted in mice showed efficacy and low toxicity of AZD7451, validating our in vitro data and stimulating more research into its clinical application. In summary, we describe in ACC a previously unrecognized pro-survival neurotrophin signaling pathway and link it with cancer progression.
10.1038/onc.2012.377
RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway.
Alonso-Curbelo Direna,Riveiro-Falkenbach Erica,Pérez-Guijarro Eva,Cifdaloz Metehan,Karras Panagiotis,Osterloh Lisa,Megías Diego,Cañón Estela,Calvo Tonantzin G,Olmeda David,Gómez-López Gonzalo,Graña Osvaldo,Sánchez-Arévalo Lobo Víctor Javier,Pisano David G,Wang Hao-Wei,Ortiz-Romero Pablo,Tormo Damià,Hoek Keith,Rodríguez-Peralto José L,Joyce Johanna A,Soengas María S
Cancer cell
Although common cancer hallmarks are well established, lineage-restricted oncogenes remain less understood. Here, we report an inherent dependency of melanoma cells on the small GTPase RAB7, identified within a lysosomal gene cluster that distinguishes this malignancy from over 35 tumor types. Analyses in human cells, clinical specimens, and mouse models demonstrated that RAB7 is an early-induced melanoma driver whose levels can be tuned to favor tumor invasion, ultimately defining metastatic risk. Importantly, RAB7 levels and function were independent of MITF, the best-characterized melanocyte lineage-specific transcription factor. Instead, we describe the neuroectodermal master modulator SOX10 and the oncogene MYC as RAB7 regulators. These results reveal a unique wiring of the lysosomal pathway that melanomas exploit to foster tumor progression.
10.1016/j.ccr.2014.04.030
SOX10-positive salivary gland tumors: a growing list, including mammary analogue secretory carcinoma of the salivary gland, sialoblastoma, low-grade salivary duct carcinoma, basal cell adenoma/adenocarcinoma, and a subgroup of mucoepidermoid carcinoma.
Hsieh Min-Shu,Lee Yi-Hsuan,Chang Yih-Leong
Human pathology
Transcription factor SRY-related HMG-box 10 (SOX10) is an important marker for melanocytic, schwannian, myoepithelial, and some salivary gland tumors. The aim of this study was to investigate SOX10 expression more thoroughly in the salivary gland neoplasms, including mammary analogue secretory carcinoma and hyalinizing clear cell carcinoma harboring specific genetic rearrangements. A new rabbit monoclonal anti-SOX10 antibody (clone EP268) was used to examine SOX10 expression in 14 different types of salivary gland tumors. We found that acinic cell carcinoma (AciCC), adenoid cystic carcinoma, mammary analogue secretory carcinoma (MASC), epithelial-myoepithelial carcinoma, low-grade salivary duct carcinoma, sialoblastoma, basal cell adenocarcinoma, basal cell adenoma, and pleomorphic adenoma were SOX10 positive. Salivary duct carcinoma, lymphoepithelial carcinoma, hyalinizing clear cell carcinoma, and oncocytoma were SOX10 negative. Earlier, mucoepidermoid carcinoma (MEC) was considered a SOX10-negative tumor. This study identified a subgroup of SOX10-positive MEC cases with characteristic polygonal epithelial cells, pale-to-eosinophilic cytoplasm, and colloid-like dense eosinophilic material. Our data show SOX10 expression can be observed in salivary gland tumors with either one of the 4 cell types: acinic cells, cuboidal ductal cells with low-grade cytologic features, basaloid cells, and myoepithelial cells. In this article we thoroughly evaluated SOX10 expression in salivary gland tumors. SOX10 is useful in the differential diagnosis between myoepithelial carcinoma with clear cell features and hyalinizing clear cell carcinoma. It can also be used to discriminate low-grade salivary duct carcinoma from high-grade ones. Pathologists should be cautious with the interpretation of SOX10 positivity in salivary gland tumors, and correlation with histologic feature is mandatory.
10.1016/j.humpath.2016.05.021
Publisher Correction: ERK-mediated phosphorylation regulates SOX10 sumoylation and targets expression in mutant BRAF melanoma.
Han Shujun,Ren Yibo,He Wangxiao,Liu Huadong,Zhi Zhe,Zhu Xinliang,Yang Tielin,Rong Yu,Ma Bohan,Purwin Timothy J,Ouyang Zhenlin,Li Caixia,Wang Xun,Wang Xueqiang,Yang Huizi,Zheng Yan,Aplin Andrew E,Liu Jiankang,Shao Yongping
Nature communications
In the original version of this Article, financial support was not fully acknowledged. The PDF and HTML versions of the Article have now been corrected to include the following: The National Basic Research Program (2015CB553602 to J.L.), the National Natural Science Foundation of China (31570777, 91649106, 31770917 to J.L.) and Tianjin Applied Basic and Frontier Tech Major Project (12JCZDJC34400 to J.L.) and Tianjin Higher Education Sci-Tech Development Project (20112D05 to J.L.).
10.1038/s41467-018-03710-1
Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma.
Shakhova Olga,Zingg Daniel,Schaefer Simon M,Hari Lisette,Civenni Gianluca,Blunschi Jacqueline,Claudinot Stéphanie,Okoniewski Michal,Beermann Friedrich,Mihic-Probst Daniela,Moch Holger,Wegner Michael,Dummer Reinhard,Barrandon Yann,Cinelli Paolo,Sommer Lukas
Nature cell biology
Giant congenital naevi are pigmented childhood lesions that frequently lead to melanoma, the most aggressive skin cancer. The mechanisms underlying this malignancy are largely unknown, and there are no effective therapies. Here we describe a mouse model for giant congenital naevi and show that naevi and melanoma prominently express Sox10, a transcription factor crucial for the formation of melanocytes from the neural crest. Strikingly, Sox10 haploinsufficiency counteracts Nras(Q61K)-driven congenital naevus and melanoma formation without affecting the physiological functions of neural crest derivatives in the skin. Moreover, Sox10 is also crucial for the maintenance of neoplastic cells in vivo. In human patients, virtually all congenital naevi and melanomas are SOX10 positive. Furthermore, SOX10 silencing in human melanoma cells suppresses neural crest stem cell properties, counteracts proliferation and cell survival, and completely abolishes in vivo tumour formation. Thus, SOX10 represents a promising target for the treatment of congenital naevi and melanoma in human patients.
10.1038/ncb2535
NOTCH1 and SOX10 are Essential for Proliferation and Radiation Resistance of Cancer Stem-Like Cells in Adenoid Cystic Carcinoma.
Panaccione Alex,Chang Michael T,Carbone Beatrice E,Guo Yan,Moskaluk Christopher A,Virk Renu K,Chiriboga Luis,Prasad Manju L,Judson Benjamin,Mehra Saral,Yarbrough Wendell G,Ivanov Sergey V
Clinical cancer research : an official journal of the American Association for Cancer Research
PURPOSE:Although the existence of cancer stem cells (CSC) in adenoid cystic carcinoma (ACC) has been proposed, lack of assays for their propagation and uncertainty about molecular markers prevented their characterization. Our objective was to isolate CSC from ACC and provide insight into signaling pathways that support their propagation. EXPERIMENTAL DESIGN:To isolate CSC from ACC and characterize them, we used ROCK inhibitor-supplemented cell culture, immunomagnetic cell sorting, andin vitro/in vivoassays for CSC viability and tumorigenicity. RESULTS:We identified in ACC CD133-positive CSC that expressed NOTCH1 and SOX10, formed spheroids, and initiated tumors in nude mice. CD133(+)ACC cells produced activated NOTCH1 (N1ICD) and generated CD133(-)cells that expressed JAG1 as well as neural differentiation factors NR2F1, NR2F2, and p27Kip1. Knockdowns ofNOTCH1, SOX10, and their common effectorFABP7had negative effects on each other, inhibited spheroidogenesis, and induced cell death pointing at their essential roles in CSC maintenance. Downstream effects ofFABP7knockdown included suppression of a broad spectrum of genes involved in proliferation, ribosome biogenesis, and metabolism. Among proliferation-linked NOTCH1/FABP7 targets, we identified SKP2 and its substrate p27Kip1. A γ-secretase inhibitor, DAPT, selectively depleted CD133(+)cells, suppressed N1ICD and SKP2, induced p27Kip1, inhibited ACC growthin vivo, and sensitized CD133(+)cells to radiation. CONCLUSIONS:These results establish in the majority of ACC the presence of a previously uncharacterized population of CD133(+)cells with neural stem properties, which are driven by SOX10, NOTCH1, and FABP7. Sensitivity of these cells to Notch inhibition and their dependence on SKP2 offer new opportunities for targeted ACC therapies.
10.1158/1078-0432.CCR-15-2208
Linking SOX10 to a slow-growth resistance phenotype.
Zhang Gao,Herlyn Meenhard
Cell research
Slow-cycling BRAF melanoma cells are notoriously resistant to standard chemotherapy or targeted therapy but the underlying mechanism remains elusive. Now a new study unlocks this mystery and offers novel insights into developing more effective therapeutic interventions.
10.1038/cr.2014.67
miR145 targets the SOX9/ADAM17 axis to inhibit tumor-initiating cells and IL-6-mediated paracrine effects in head and neck cancer.
Yu Cheng-Chia,Tsai Lo-Lin,Wang Mong-Lien,Yu Chuan-Hang,Lo Wen-Liang,Chang Yun-Ching,Chiou Guang-Yuh,Chou Ming-Yung,Chiou Shih-Hwa
Cancer research
ALDH1(+)CD44(+) cells are putative tumor-initiating cells (TIC) in head and neck squamous cell carcinomas (HNC). miR-145 regulates tumorigenicity in various cancers but the breadth of its mechanistic contributions and potential therapeutic applications are not completely known. Here, we report that ALDH1(+)CD44(+)-HNC cells express reduced levels of miR145. SPONGE-mediated inhibition of miR-145 (Spg-miR145) was sufficient to drive tumor-initiating characteristics in non-TICs/ALDH1(-)CD44-negative HNC cells. Mechanistic analyses identified SOX9 and ADAM17 as two novel miR145 targets relevant to this process. miR-145 expression repressed TICs in HNC in a manner associated with SOX9 interaction with the ADAM17 promoter, thereby activating ADAM17 expression. Notably, the SOX9/ADAM17 axis dominated the TIC-inducing activity of miR-145. Either miR-145 suppression or ADAM17 overexpression in non-TICs/ALDH1(-)CD44(-)-HNC cells increased expression and secretion of interleukin (IL)-6 and soluble-IL-6 receptor (sIL-6R). Conversely, conditioned medium from Spg-miR145-transfected non-TICs/ALDH1(-)CD44(-)-HNC cells was sufficient to confer tumor-initiating properties in non-TICs/ALDH1(-)CD44(-)-HNC and this effect could be abrogated by an IL-6-neutralizing antibody. We found that curcumin administration increased miR-145 promoter activity, thereby decreasing SOX9/ADAM17 expression and eliminating TICs in HNC cell populations. Delivery of lentivral-miR145 or orally administered curcumin blocked tumor progression in HNC-TICs in murine xenotransplant assays. Finally, immunohistochemical analyses of patient specimens confirmed that an miR-145(low)/SOX9(high)/ADAM17(high) phenotype correlated with poor survival. Collectively, our results show how miR-145 targets the SOX9/ADAM17 axis to regulate TIC properties in HNC, and how altering this pathway may partly explain the anticancer effects of curcumin. By inhibiting IL-6 and sIL-6R as downstream effector cytokines in this pathway, miR-145 seems to suppress a paracrine signaling pathway in the tumor microenvironment that is vital to maintain TICs in HNC.
10.1158/0008-5472.CAN-12-3840
Gene Expression Profiling of Head and Neck Tumors Identifies FOXP1 and SOX10 Expression as Useful for Distinguishing Ameloblastoma From Basaloid Salivary Gland Tumors.
The American journal of surgical pathology
Odontogenic tumors show considerable morphologic heterogeneity and at times the diagnosis can be challenging. Ameloblastoma, the most common odontogenic tumor, can have morphologic similarity to some salivary gland tumors and therefore we sought to identify biomarkers that might aid in the diagnosis by performing transcriptome wide gene expression profiling of 80 odontogenic and salivary gland neoplasms. These data identified the FOXP1/SOX10 expression profile as characteristic of many odontogenic tumors including ameloblastoma but largely absent in salivary gland tumors. We then assessed 173 salivary gland tumors and 108 odontogenic tumors by immunohistochemistry for FOXP1 and SOX10 expression and found that 34/35 (97%) cases of ameloblastomas were diffusely positive for FOXP1 but completely negative for SOX10. None of the basaloid salivary neoplasms (basal cell adenoma, adenoid cystic carcinoma, polymorphous adenocarcinoma, and myoepitheloma) demonstrated FOXP1/SOX10 expression pattern. Taken together, the results of this study suggest that the FOXP1/SOX10 immunophenotype is common in odontogenic tumors including ameloblastoma and might be useful distinguishing these from similar appearing basaloid salivary gland tumors.
10.1097/PAS.0000000000001421
Expression of Sox10 and c-kit in sinonasal mucosal melanomas arising in the Chinese population.
Liu Hong Gang,Kong Max Xiangtian,Yao Qian,Wang Shu Yi,Shibata Robert,Yee Herman,Martiniuk Frank,Wang Beverly Y
Head and neck pathology
Sinonasal mucosal melanomas (SNMM) of the head and neck regions are rare and aggressive malignancies. Although they can affect patients of any ethnicity, they are more numerous in Chinese patients. The diagnosis and treatment of these tumors can be challenging. Recent studies have reported that Sox10 is a sensitive melanocytic marker for cutaneous melanoma (Nonaka et al. in Am J Surg Pathol 32:1291-1298, 2008). In addition, a CD117 (c-kit) gene mutation has been identified in cutaneous melanomas, indicating that there may be potential therapeutic benefits of tyrosine kinase inhibitors, such as Imatinib. The purpose of this study was to detect and test the immunohistochemical expression of Sox10 and c-kit in mucosal melanomas (MM) arising in the nasal cavities of Chinese patients. Twenty eight patients with mucosal melanomas of the nasal cavity were treated in two major hospitals in China. All cases had been locally diagnosed as primary SNMM. We confirmed all diagnoses with positive immunohistochemical stains for S100 and HMB-45. Additionally, automated immunohistochemistry was performed using a goat polyclonal Sox10 antibody and a monoclonal c-kit antibody counterstained using a standard avidin-biotin complex method. Immunohistochemical positive expression of Sox10 was defined by nuclear stain; and positivity for c-kit resulted in a distinct membranous staining. The extent of nuclear positivity for Sox10 and membranous stain for c-kit was graded by 4 board certified pathologists as follows: 1+, 1-25 % of positive tumor cells; 2+, 25-50 %; 3+, 50-75 %; and 4+, ≥75 %. Sox10 nuclear expression was found in all cases (100 %), with 4+ staining in 26 out of 28 cases (92.8 %) and 3+ staining in two cases with (7.1 %). The overall positivity for S100 staining was 23 out of 28 (82.1 %), with 1+ staining in 10 cases, 2+ staining in 6 cases, 3+ staining in 7 cases, and no staining in 5 cases. The sensitivity and intensity of Sox10 immunohistochemistry were both higher than with S100 immunohistochemistry. Immunopositivity of membranous stain for c-kit (CD117) was seen in 24 out of 28 cases (85.7 %), including 6 tumors that were 4+, eight that were 3+, six that were 2+, and four that showed 1+ staining. Our results demonstrate that Sox10 is a sensitive marker for SNMM and it may possess diagnostic value in addition to that of S100 protein. The expression of c-kit in the majority of MMs suggests that it may be useful in the assessment of these tumors for potential treatment with tyrosine kinase inhibitors.
10.1007/s12105-012-0375-2
Rare variants of head and neck squamous cell carcinoma -differential immunohistochemical profiles.
Allon Irit,Vered Marilena,Kaplan Ilana,Nahlieli Oded,Yahalom Ran,Shalmon Bruria,Srouji Samer,Livoff Alejandro
Acta histochemica
We aimed to immunohistochemically characterize the pattern of expression of epithelial markers in rare head and neck squamous cell carcinoma (HNSCC) variants: carcinoma cuniculatum (CC) and adenosquamous carcinoma (ASC). We also present an additional variant of HNSCC with concomitant basaloid and squamous components that has overlapping morphological features with odontogenic and non-odontogenic tumors, which we termed basalo-squamous carcinoma (BSC). The selected markers included CK5/6, p40, CK19, BerEP4, p16 and SOX10. All tumors were CK5/6 and p40 positive. CK19 and BerEP4 were positive in BSC and focally in ASC but negative in CC. p16 was positive in 3 (60%) of the CCs, focally positive in ASC and negative in BSC. SOX10 was negative in all three variants. Our results highlight the plasticity of the lining epithelium revealing differential profiles of immuno-expression of the selected molecular markers, possibly reflecting their diverse histopathogenesis.
10.1016/j.acthis.2019.151444
Sox10--a marker for not only schwannian and melanocytic neoplasms but also myoepithelial cell tumors of soft tissue: a systematic analysis of 5134 tumors.
Miettinen Markku,McCue Peter A,Sarlomo-Rikala Maarit,Biernat Wojciech,Czapiewski Piotr,Kopczynski Janusz,Thompson Lester D,Lasota Jerzy,Wang Zengfeng,Fetsch John F
The American journal of surgical pathology
Sox10 transcription factor is expressed in schwannian and melanocytic lineages and is important in their development and can be used as a marker for corresponding tumors. In addition, it has been reported in subsets of myoepithelial/basal cell epithelial neoplasms, but its expression remains incompletely characterized. In this study, we examined Sox10 expression in 5134 human neoplasms spanning a wide spectrum of neuroectodermal, mesenchymal, lymphoid, and epithelial tumors. A new rabbit monoclonal antibody (clone EP268) and Leica Bond Max automation were used on multitumor block libraries containing 30 to 70 cases per slide. Sox10 was consistently expressed in benign Schwann cell tumors of soft tissue and the gastrointestinal tract and in metastatic melanoma and was variably present in malignant peripheral nerve sheath tumors. In contrast, Sox10 was absent in many potential mimics of nerve sheath tumors such as cellular neurothekeoma, meningioma, gastrointestinal stromal tumors, perivascular epithelioid cell tumor and a variety of fibroblastic-myofibroblastic tumors. Sox10 was virtually absent in mesenchymal tumors but occasionally seen in alveolar rhabdomyosarcoma. In epithelial tumors of soft tissue, Sox10 was expressed only in myoepitheliomas, although often absent in malignant variants. Carcinomas, other than basal cell-type breast cancers, were only rarely positive but included 6% of squamous carcinomas of head and neck and 7% of pulmonary small cell carcinomas. Furthermore, Sox10 was often focally expressed in embryonal carcinoma reflecting a primitive Sox10-positive phenotype or neuroectodermal differentiation. Expression of Sox10 in entrapped non-neoplastic Schwann cells or melanocytes in various neoplasms has to be considered in diagnosing Sox10-positive tumors. The Sox10 antibody belongs in a modern immunohistochemical panel for the diagnosis of soft tissue and epithelial tumors.
10.1097/PAS.0000000000000398
SOX9 promotes nasopharyngeal carcinoma cell proliferation, migration and invasion through BMP2 and mTOR signaling.
Xiao Bin,Zhang Weiyun,Kuang Zhenzhan,Lu Jingrun,Li Weiwei,Deng Chun,He Yongyin,Lei Ting,Hao Wenbo,Sun Zhaohui,Li Linhai
Gene
SRY-related high-mobility-group box 9 (SOX9) is a member of the SOX family of transcription factors. Accumulating evidence has shown that SOX9 plays a significant role in various malignancies. However, the role of SOX9 in nasopharyngeal carcinoma (NPC) remains unknown. In the present study, up-regulation of SOX9 was observed in both NPC tissues and different NPC cells. Overexpression of SOX9 promoted NPC cell proliferation, migration and invasion. Conversely, knock down of SOX9 inhibited NPC proliferation, colony formation, migration and invasion. Mechanistically, SOX9 bound directly to the promoter region of BMP2 and increased BMP2 expression. In addition, overexpression of SOX9 activated the mTOR pathway partly through BMP2. Collectively, these results identify a novel role for SOX9 as a potential therapeutic marker for the prevention and treatment of NPC.
10.1016/j.gene.2019.144017
High expression of Sox10 correlates with tumor aggressiveness and poor prognosis in human nasopharyngeal carcinoma.
Zhao Yu,Liu Zhi-Gang,Tang Jiao,Zou Ren-Fang,Chen Xiao-Yan,Jiang Guan-Min,Qiu Yan-Fang,Wang Hui
OncoTargets and therapy
PURPOSE:The aim of the study was to detect the expression of Sox10 in human nasopharyngeal carcinoma (NPC) and investigate the relationship between its expression and the clinicopathological characteristics of NPC patients. PATIENTS AND METHODS:Tumor specimens (n=105) were retrospectively collected from patients with NPC diagnosed between 2004 and 2005 who presented at Hunan Cancer Hospital. Immunohistochemistry analyses were performed to characterize the expression of Sox10 in NPC. Kaplan-Meier survival and Cox regression analyses were employed to evaluate the prognosis of 105 NPC patients. RESULTS:The results showed that Sox10 was markedly overexpressed in human NPC tissues. Analysis of clinicopathological parameters showed that high Sox10 expression was significantly correlated with the clinical stage (P=0.032), T classification (P=0.034), and lymph node metastasis (P=0.03). Cox regression analyses further showed that Sox10 expression was an independent prognostic factor for overall survival (P=0.005). This is the first time Sox10 has shown its importance in predicting NPC progressiveness and survival outcomes. CONCLUSION:Sox10 serves as a potential biomarker for NPC patients. It may hopefully become a novel therapeutic target for NPC patients.
10.2147/OTT.S101344
Sox10: a pan-schwannian and melanocytic marker.
Nonaka Daisuke,Chiriboga Luis,Rubin Brian P
The American journal of surgical pathology
S100 protein is a sensitive marker for melanomas and peripheral nerve sheath tumors. It is, however, expressed by other mesenchymal and epithelial tumors. Despite its low specificity, S100 protein is valuable for the diagnosis of desmoplastic melanomas and peripheral nerve sheath tumors, for which no specific marker is available. Sox10 is a neural crest transcription factor crucial for specification, maturation, and maintenance of Schwann cells and melanocytes. Anti-Sox10 antibody was applied to a variety of neural crest-derived tumors, mesenchymal and epithelial neoplasms, and normal tissues. Sox10 nuclear expression was found in 76 of 78 melanomas (97%) and 38 of 77 malignant peripheral nerve sheath tumors (49%) whereas S100 protein was expressed in 71 melanomas (91%) and 23 malignant peripheral nerve sheath tumors (30%). Sox10 was diffusely expressed in schwannomas and neurofibromas. Sox10 reaction was seen only in sustentacular cells of pheochromocytomas/paragangliomas, and occasionally carcinoid tumors from various organs, but it was not seen in the tumor cells. In normal tissues, Sox10 was expressed in Schwann cells, melanocytes, and myoepithelial cells of salivary, bronchial, and mammary glands. Sox10 reaction was not identified in any other mesenchymal and epithelial tumors except for myoepitheliomas and diffuse astrocytomas. Sox10 was expressed by metastatic melanomas and nodal capsular nevus in sentinel lymph nodes, but not by other lymph node components such as dendritic cells. Our results indicate that Sox10 will serve as a more sensitive and specific marker for the diagnosis of melanocytic and schwannian tumors than S100 protein.
10.1097/PAS.0b013e3181658c14
[CK7, CK20, SOX10 and CDX2: expressions and diagnostic values in primary adenocarcinoma of the sinonasal tract].
Yue Changli,Piao Yingshi,Bai Yuping,Liu Honggang,Zhang Luo
Zhonghua yi xue za zhi
OBJECTIVE:To explore the expressions of the cytokeratin 7 (CK7), cytokeratin 20 (CK20), SOX10 and cadual type homeobox transcription factor 2 (CDX2) in primary adenocarcinoma of the sinonasal tract, and evaluate their diagnostic values. METHODS:A total of 41 paraffin-embeded specimens of primary adenocarcinoma of the sinonasal tract treated in Beijing Tongren Hospital of Capital Medical University were selected from May 2002 to January 2015. All cases were confirmed by histology and clinical data, including 12 cases of non-intestinal sinonasal adenocarcinomas (non-ITACs), 10 cases of intestinal sinonasal adenocarcinomas (ITACs) and 19 cases of salivary gland-type adenocarcinomas (including 12 cases of adenoid cystic carcinomas, 3 cases of polymorphous low grade adenocarcinomas, 2 cases of mucinous adenocarcinomas and 2 cases of acinar cell carcinomas). Expressions of CK7, CK20, SOX10 and CDX2 were assessed by immunohistochemistry staining method. RESULTS:Nuclear staining for CDX2 was identified in all the ITACs,including diffuse nuclear staining in 8 cases and partial nuclear staining in 2 cases. Cytoplasmic staining for CK20 was identified in 9 cases of ITACs, and partial cytoplasmic staining was found in 1 case of non-ITACs, while CK20 was negative in all other adenocarcinomas.Seven cases of ITACs were negative for CK7, while CK7 was positive in all other adenocarcinomas. CK7, but not CDX2 and CK20, was expressed in normal sinonasal epithelium. SOX10 was negative in 10 cases of ITACs and 2 cases of non-ITACs, and positive in all other adenocarcinomas. The sensitivity of CK7-, CK20+, SOX10- and CDX2+ in primary ITACs of the sinonasal tract were 70.0%, 90.0%, 100%, 100%, respectively, and the specificity were 100%, 96.8%, 93.5%, 100%, respectively. CONCLUSIONS:Expressions of CK7-, CK20+, SOX10- and CDX2+ have high sensitivity and specificity in ITACs and can be used as a reliable diagnostic marker for primary intestinal-type adenocarcinoma of the sinonasal tract. Additionally, diagnostic value of CDX2 in primary intestinal-type adenocarcinoma of the sinonasal tract is superior to CK20, CK7 and SOX10.