With the substantial increase in the incidence of breast carcinoma, more and more women are suffering from breast cancer. Breast carcinoma is a highly heterogeneous disease and constitutes different molecular subtypes, which are HER2, luminal A, luminal B, claudin-low, and basal-like types. Most of TNBCs were included in the basal-like subtype. Moreover, the different molecular types of breast cancer exhibit distinct molecular mechanisms and act as biologically distinct entities that require different therapeutic management. Besides, survival analysis revealed a poor prognosis in patients diagnosed with basal-like type while the two ER + groups showed a variable outcome.
If we encounter TNBC with a high grade of tumors without ductal carcinoma in situ, particularly metastatic TNBC, and is often difficult to diagnose. Therefore, apart from recognizing the clinical course, some specific immunohistochemical markers are needed to further confirm the diagnosis. Presently, ER, GCDFP15 and MGB are the most commonly used markers in the diagnosis of breast carcinoma. However, recently, an increasing number of studies have considered GATA-3 as a useful marker in breast carcinoma [12–17]. FOXA1 is known for molecular subtyping of breast carcinoma and its expression is associated with good clinical outcomes and is also considered as a molecular marker for breast carcinoma diagnostics . More recently, Sox10 with more than 20 SOX family transcription factors has been characterized by HMG DNA binding domain sequence and recognized to play a crucial role in the development of the nervous system, immune system, and skeletal system .
Existing studies suggested that Sox10 plays an important role in assisting the diagnosis of melanoma, peripheral nerve-derived tumor, and salivary gland myoepithelial tumors. Notably, Sox10 is a sensitive lineage marker for both primary and metastatic TNBC; however, the diagnostic value of Sox10 in TNBC remains to be elucidated. Notch signaling pathway plays a central link in maintaining stem cell characteristics and regulating cell differentiation in breast tissue . Notch gene is usually activated in glandular precursor cells of breast lobules . In vitro studies on mouse mammary epithelial cells revealed that Notch4-PBP mediated cell proliferation required the involvement of Sox10, however, the other roles of Sox10 in the differentiation and development of mammary epithelial cells remain elusive . Studies showed that Sox10 was only expressed in myoepithelial cells of normal breast tissue by IHC method, but not in other cells . In this study, we also found that Sox10 was only expressed in the myoepithelial cells around the lobules and ducts in normal breast tissue, but not in the other lumen cells. Consistently, it was also localized in the nucleus, as reported previously. Myoepithelial cells exist not only in the breast but also in many tissues, including soft tissue, salivary gland. Sox10 expression was detected in salivary gland myoepithelial tumors such as acinar cell carcinoma, adenoid cystic carcinoma, myoepithelial carcinoma, and epithelial-myoepithelial carcinoma; however, not in mucoepidermoid carcinoma and ductal carcinoma from the non-myoepithelial origin [28, 29]. Miettinen et al  also suggested that Sox10 was not only a diagnostic marker for schwannoma and malignant melanoma, but also expressed in myoepithelial tumors in soft tissue. Considering the results from these studies, we can conclude that Sox10 is a good diagnostic marker for myoepithelial tumors, and the expression of Sox10 may suggest that the tumors may originate from myoepithelium.
Furthermore, Cimino-Mathews A , Ivanov SV  and others have found that Sox10 can be expressed in primary breast carcinoma, predominantly in basal-like breast carcinoma and unclassified TNBC. Recently, an IHC based study has been demonstrated Sox10 as an additional marker in TNBC, especially for basal-like and metaplastic subtype. Similarly, we also found a significantly higher positive rate of Sox10 in primary and metastatic TNBC than in other two types (P < 0.001, P < 0.001, respectively), which was consistent with the findings of the previously reported literature. TNBC is considered to be a malignant tumor originating from breast myoepithelial cells, which explains why Sox10 is more positive in TNBC than in other types of breast carcinoma. The characteristic of TNBC is that ER, PR, and Her2 are not expressed and the heterogeneity is very high. TNBC has been characterized as exhibiting a negative profile for the three markers, therefore, treatment of this molecular sub-type remains highly challenging. Consequently, a large number of studies on TNBC mainly focused on deciphering novel therapeutic targets and strategies. Pathological diagnosis of TNBC remains the gold standard for pathological diagnosis. Since ER, PR, and Her2 are not expressed in TNBC, these three markers cannot be used to differentiate them from metastatic adenocarcinoma. In addition, through literature reviews and from this study, we demonstrated that besides GATA-3, FOXA1, GCDFP15, and MGB, which are most extensively used markers for routine diagnosis of breast carcinoma, exhibit low sensitivity, and specificity in distinguishing primary TNBC and metastatic TNBC. Thus, by comparing the sensitivity and specificity of expression of Sox10 with that of GATA-3, FOXA1, GCDFP15, MGB in TNBC, this study revealed that the sensitivity and specificity of Sox10 were significantly higher than those of the other three markers (P < 0.001, P = 0.0004, P = 0.0064, P = 0.0229, respectively) for both primary and metastatic TNBC. Therefore, this indicated that the sensitivity and specificity of Sox10 for TNBC were remarkably high. In routine immunohistopathology, expression of Sox10 combined with GATA-3 may serve as a promising putative immunohistochemical marker for the diagnosis of TNBC, particularly, for metastatic TNBC.
Accumulating studies have suggested that Soxl0 plays an important role in the occurrence and development of various tumors, and participates in the proliferation, migration, and invasion of tumor cells [32, 33, 34]. Owing to differences in the expression level of Sox10 in a variety of tumors, its effect on cell function is also differently attributable to differences in mechanisms. Sox10 is overexpressed in nasopharyngeal carcinoma  and bladder cancer , which promotes the growth and metastasis of tumors and plays an oncogenic role. However, in many digestive tract tumors, the expression of Sox10 is low and plays the role of tumor suppressor . However, presently there are limited clinical studies on the role of Sox10 in the occurrence and development of primary TNBC. By analyzing the correlation between the expression of Sox10 protein and clinicopathological characteristics in 71 cases of primary TNBC, the present study revealed that the positive rate of Sox10 protein was significantly correlated with pathological grade, clinical stage and a number of lymph node metastasis. The positive rate of Sox10 expression was higher in high-grade TNBC compared to low-grade TNBC (P = 0.0145), the positive rate of Sox10 expression in late-stage TNBC was remarkably higher than that of early-stage TNBC (P = 0.0105), and the positive rate of Sox10 expression was significantly higher in cases with less number of lymph node metastasis than that of more number of lymph node metastasis (P = 0.0249). Based on these findings, we speculated that Sox10 also plays an oncogenic role in the occurrence and development of TNBC. The prognosis of tumors is related to many factors, including the stage of tumors, the number of lymph node metastases, pathological grading, and tumor size. The later the stage, the worse the prognosis of the tumors; the higher the pathological grade, the worse the prognosis; similarly, a higher number of lymph node metastasis is also considerably associated with the prognosis of TNBC. There is a growing body of evidence which demonstrates that more the involvement of the lymph node, the more prone the tumors to metastasis and recurrence. Since the expression of Sox10 protein is correlated with tumor stage, number of lymph node metastasis and pathological grade of primary TNBC in this study, the present study indicated that the expression of Sox10 protein is highly associated with the adverse prognosis of primary TNBC, and may serve a novel putative biomarker for predicting the prognosis and metastasis of primary TNBC and potential target genes for the treatment of TNBC. Further follow-up of the patients with primary TNBC revealed that the 5-year disease-free survival period of the patients with Sox10 protein-positive was significantly lower than that with the negative expression (P = 0.00008). This finding further confirmed our hypothesis that the high expression of Sox10 can be used as an index to predict the prognosis of patients with TNBC. Conceivably, the high expression of Sox10 was an independent predictor of TNBC. Thus, identifying the expression of Sox10 through IHC technique can be used as a supplementary diagnostic marker for risk prediction.
In conclusion, the findings of this preliminary study suggested that Sox10 expression is a novel prognostic biomarker for TNBC and highlight the clinical significance of targeting Sox10 as a promising potential therapeutic target gene for TNBC therapy. Further studies on larger sample size are warranted at RNA levels to establish these findings.