Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas

Abstract

Summary The transcription factor Sox10 mediates the differentiation of neural crest–derived cells, and Sox10 labeling by immunohistochemistry (IHC) is used clinically primarily to support the diagnosis of melanoma. Sox10 expression by IHC has been previously documented in benign breast myoepithelial cells but not in breast carcinomas. Here, we report the first systematic study of Sox10 expression in invasive ductal carcinomas subclassified by IHC-defined molecular subtype (100 cases), as well as in 24 cases of ductal carcinoma in situ and 44 mammary fibroepithelial neoplasms. Tissue microarrays containing 168 primary breast tumors were subjected to IHC for Sox10. The extent of nuclear Sox10 labeling was scored by percentage labeling as follows: 0 (0%), 1+ (1%–25%), 2+ (25%–50%), 3+ (50%–75%), and 4+ (>75%). Overall, 40 (40%) of 100 invasive breast carcinomas demonstrated Sox10 immunoreactivity, which was seen primarily in the basal-like, unclassified triple-negative, and metaplastic carcinomas. Sox10 labeling was seen in 66% (38/58) of the basal-like, unclassified triple-negative, and metaplastic carcinomas as compared with 5% (2/42) of the luminal A, luminal B, and Her-2 carcinomas (P < .00001). Sox10 labeling was seen in 1 (4%) of 24 cases of ductal carcinoma in situ, which was negative for estrogen receptor/progesterone receptor. No labeling was seen in the stromal component of phyllodes tumors or fibroadenomas. These findings show that breast carcinoma must be considered in the differential diagnosis of melanoma for an S100-positive, Sox10-positive metastatic malignant neoplasm. Sox10 expression in the basal-like, unclassified triple-negative, and metaplastic carcinomas types supports the concept that these neoplasms show myoepithelial differentiation.

Signaling Pathways in the Development of Infantile Hemangioma

“…activate an endogenous autoregulatory network in adult stem cells and reconstitute an entire mammary gland (Guo et al 2012). Meanwhile, showing stem cell characteristics such as self-renewal and multi-potency, Sox10 is one of the most studied Sox family genes, mainly because of their role in the survival of neural crest cells and compilation into neural-crest-derived melanocytes and glia (Cimino-Mathews et al 2013;Ivanov et al 2013). Invasive breast carcinomas, especially those with triple negative hormone expression and metastases seem to be supportive for myoepithelial differentiation (CiminoMathews et al 2013;Ivanov et al 2013).…”

“…Sox9, Sox10 and Slug were shown to be associated with poor overall survival in breast cancer (Cimino-Mathews et al 2013;Guo et al 2012).…”

“…Recently Sox10 labeling has been documented in myoepithelial differentiated cells in salivary gland neoplasms and also in metaplastic triple negative breast cancers (Cimino-Mathews et al 2013;Ivanov et al 2013).…”

Novel uses of immunohistochemistry in the diagnosis and classification of soft tissue tumors

“…22,24 Reactivity for SOX10 is also observed in astrocytomas, myoepithelial tumors, selected other types of salivary gland neoplasms, and a subset of breast carcinomas, particularly basal-like, 'triple-negative, ' and metaplastic carcinomas. 21,25,26 The most recent addition to this group of markers is SATB2 (special AT-rich sequence-binding protein 2).…”

Diagnostic utility of SOX10 to distinguish malignant peripheral nerve sheath tumor from synovial sarcoma, including intraneural synovial sarcoma

“…18,19 Previous studies have shown that the expression of this nuclear transcription factor, detected by immunohistochemistry, is sensitive for a variety of Schwannian and melanocytic neoplasms, [20][21][22] benign myoepithelial cells and rarely other tumor types. 23 However, data specifically comparing genetically confirmed synovial sarcoma, including intraneural synovial sarcoma, with malignant peripheral nerve sheath tumor with respect to SOX10 expression is limited. In the present study, we evaluate the utility of SOX10 immunohistochemistry in differentiating malignant peripheral nerve sheath tumor from synovial sarcoma.…”