The neural crest transcription factor SOX 10 is preferentially expressed in triple negative breast carcinomas

Antonio Arra1 image Daniel Coso1

Rosana Ramos Dos Santos1

1 Universidad Abierta Interamericana. Facultad de Medicina y Ciencias de la Salud. Buenos Aires, Argentina.

Envelope Quirno 223 4ºa, CABA, CP 1406 /


Fecha de recepción: febrero de 2021. Fecha de aceptación: junio de 2021.


Background: The expression of SOX 10 by immunohistochemistry has been documented in benign breast myoepithelial cells and in ductal carcinomas classified by the molecular subtype defined by immunohistochemis- try. Material and methods: 77 cases of infiltrating ductal carcinomas of the mammary gland with Sox 10 reactivi- ty were analyzed and subdivided by immunohistochemistry into the different molecular subtypes. The IHC panel used to define the molecular subtypes included Estrogen Receptors (R.E), Progesterone Receptors (R.P), Her 2, Cytokeratin (C.K) 5/6, Epidermal Growth Factor Receptor (E.G.F.R). Results: In our study we demonstrated in 31 cases (44.25%) of 77 infiltrating ductal carcinomas SOX 10 immunoreactivity, which was observed only in basal and undifferentiated subtype triple negative carcinomas. Conclusion: The expression of Sox 10 in triple infiltrating ductal carcinomas Negative supports the concept that these neoplasms show myoepithelial differentiation.


Breast carcinoma, Triple Negative, SOX10, Ductal carcinomas, Myoepithelial cells


El factor de transcripción de la cresta neural SOX 10 se expresa preferentemente en los carcinomas de mama triple negativos


Introducción: La expresión de SOX 10 por inmunohistoquímica ha sido documentada en células mioepitelia- les de mama benignas y en carcinomas ductales clasificados por el subtipo molecular definido por inmunohisto- química. Material y métodos: Se analizaron 77 casos de carcinomas ductales infiltrantes de glándula mamaria con reactividad Sox 10 y se subdividieron por inmunohistoquímica en los diferentes subtipos moleculares. El panel de IHC utilizado para definir subtipos moleculares incluyó receptores de estrógeno (ER), receptores de progesterona (PR), Her 2, citoqueratina (CK) 5/6, receptor del factor de crecimiento epidérmico (EGFR). Re- sultados: En nuestro estudio demostramos en 31 casos (44,25%) de 77 carcinomas ductales infiltrantes la in-


Este trabajo está bajo una Licencia Creative Commons Atribución 4.0 Internacional.

munorreactividad SOX 10, que solo se observó en carcinomas basales e indiferenciados subtipo triple negativo. Conclusión: La expresión de Sox 10 en carcinomas ductales infiltrantes triple negativos apoya el concepto de que estas neoplasias muestran diferenciación mioepitelial.


Carcinoma de mama, Triple negativo, SOX10, Carcinomas ductales, Células mioepiteliales



The transcription factor Sox 10 is involved in the survival and differentiation of glial cells and mela- nocytes [1,2]. The antibody Sox 10 uses by inmu- nohistoqu í mica (IH Q), mainly for precis ar diag- nosis of melanoma [3-5] and your Mores nerve sheaths [3,4]. Both of which are interpreted to derive from the neural crest.

Expression of Sox 10 by IHC has been documen- ted in breast myoepithelial cells, salivary glands, and bronchial glands [3,4].

Ashley- Cimino - Mathew s et al. [6], published the expression of Sox 10 in infiltrating ductal carcino- mas previously subclassified in the different molecu- lar subtypes.

Our objective consisted in evaluating the expression of Sox 10 ductal carcinomas, subdivided by IHC 5 molecular subtypes: Luminal A, Lum inal B, Her 2 and negative Triple with two variants similar basal and Undifferentiated and assessing whether the do- minant expression this marker and n triple negative could lead one to conclude its origin in cells myoepi- thelial these neo p lasias.


IHC panel used to define molecular subtypes inclu- ded Receptors Estrogens (RE.), Progesterone recep- tor (R. P.), Her 2, cytokeratin (CK) 5/6, Receptor Growth Factor Epidermal (EGFR) [7].

vels of Ki 67 <14%.

Luminal carcinoma

                  type       B             


0 (0%

Her2 enriched breast carcinomas are RE. and RP. ne-

gative and Her 2 positive.

Her 2 Carcinoma


0 (0%


Luminal A breast carcinomas are positive for hormo- ne receptors (ER Positive and / or PR Positive), nega- tive for Her2 and have low levels of Ki 67 (> 14%). Luminal B breast carcinomas are positive for hormo- ne receptors (ER. Positive and / or PR. Positive) and positive for Her2 or negative for Her2 with high le-

Triple negative breast carcinomas are ER negative, RP. and Her 2. In turn, a subtype of this type of carci- noma express CK 5/6 and EGFR and are called basal types and another subtype that does not express CK5

/ 6 and EGFR are called undifferentiated or quadru- ple negative.

We evaluated the expression of Sox 10 in a total of 77 cases of infiltrating duct carcinomas of the mammary gland, subdivided by IHC into the different molecular subtypes. 27 undifferentiated triple negative carcino- mas, 21 cases of baseline type triple negative, 10 Lu- minal A, 10 Luminal B and 9 Her2 3+ (Positive).

IHC techniques were performed with the anti- body polyclonal Sox 10 obtained in rabbit, with a dilution of 1 in 100, Brand Cell Marque, a auto- mator of immunostaining Bench mark GX, Brand Window.

SOX 10 staining was observed at the level nu- clear in carcinomas du infiltrating ctales mammary gland. As a positive internal control, strong Sox 10 nu- clear staining was observed in the myoepithelial cells of the mammary gland at the level of the normal lobules.


Expression of Sox 10 was observed in 16 of 27 undi- fferentiated triple negative carcinomas (59.25%).

In 15 of 21 baseline triple negative carcinomas (71.42%). In the 10 Luminal A, 10 Luminal B and 9 Her2 3+. N or expression was observed for Sox 10.

(Table 1). Immunohistochemistry of Sox 10 breast



N ° Cases TotalPositives


Luminal Carcinoma Type A 10 0 (0%





BasalTripleNegativeCarcinoma 21 15(71.42%)



27 16(54.25%)














The Sox genes are a family of transcription fac- tors with HMG-DNA-binding domains that play a role in numerous developmental processes, including the development of the nervous system, skeletal sys- tem, and immune system [8]. The Sox 10 gene was first discovered in mouse embryos in 1993 [9] and was subsequently described in the human genome in 1998 [10]. All family proteins Sox, the function of Sox10 protein has been one of the most studied, lar- gely due to the association of Sox 10 mutated neu- roc ristopatias clinical like syndrome Waarden- burg-Shah [2] . Sox 10 appears to play a role in the survival of neural crest cells and in their maturation and differentiation into neural crest-derived melano- cytes and glia [1,2].

In the breast, via Notch signaling it is essential for controlling the maintenance of stem cells and cell differentiation [11], and the Notch gene is activa- ted in progenitor cells luminal duct signals of lo- bes breast [12]

The immunostaining with Sox 10 IHC demonstra- ted in cells myoepithelial breast [3,4] but in Sickle Cell ductal epithelial benign s.

Ashley- cimino - Mathew s et al [6] demonstrated for the first time nuclear marking with S ox 10 by SSI in infiltrating breast carcinoma, more precisely in 66% of basal subtype triple negative breast carcinomas and in unclassifiable ones. not observed reactivida- dad with Sox 10 and n carcinomas luminal A, and very limited in carc inomas luminal B and carcino-

mas Her2.

In our work we have shown by dialing Sox10 by im- munohistochemistry infiltrating breast carcinomas, more exactame nte in 64.58% of carcinom as triple

- negative breast, basal subtype and the unclassifia- ble.

We did not observe reactivity with sox 10 with lumi- nal A, luminal B, Her 2 carcinomas.

Triple negative breast carcinomas are a heteroge- neous group of infiltrating carcinomas that lack ex- pression of RE, R. P, and Her2 [13,14]. Currently there is no specific targeted therapy for these tumors and as a group, they are associated with poor overall survival.

Basal-type tumors comprise a subset of triple ne- gative carcinoma, because they lack expression of RE, RP, and Her2 and express markers seen in ba- sal myoepithelial cells of the breast such as CK 5 / 6 and / or E.G.F.R.[15,16]. Our findings on the ex- pression of Sox 10 in a subset of infiltrating breast carcinomas present us with several points:

First: The expression of sox 10 in nor- mal breast myoepithelial cells, as well as in tri- ple negative carcinomas, basal subtype supports the myoepithelial differentiation of these types of neoplasms.

Second: it also suggests that unclassifiable triple negative carcinomas have demonstrated reactivity with sox 10 and also evidenced a basal or myoepi- thelial differentiation, which is not detected by IHC with EGFR or Ck 5/6.

Third: Immunoreactivity for Sox 10 may be useful to pinpoint a mammary origin of a metastasis from a basal or undifferentiated triple negative carcinoma. A study in the inst itutu Salk study biological s found that the gene Sox 10 is expressed as specific in mammary cells showing typical activity of stem cells or progenitors, ie those with greater capacity to generate cell types.

Furthermore, analysis of Sox 10 expression in a panel of breast tumor samples revealed a tendency for triple nega- tive breast cancers to present higher Sox 10 levels than the rest of the tumors.

The resulting two of this work indicate an IM plication of the g in Sox 10 in the acquisition of cellular characteristics that favors aggressiveness and spread of tumors triple nega- tive breast and point to new ways about the need to investi- gate the development of trafficking ment for the same [17].


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