SOX11 and Epithelial-Mesenchymal Transition in Metastatic Serous Ovarian Cancer

Abstract

Background: Ovarian cancer is the leading cause of death from gynecological malignancies, with serous carcinoma being the most common histopathologic subtype. Epithelial-mesenchymal transition (EMT) correlates with increased metastatic potential, whereas the transcription factor SRY-box transcription factor 11 (SOX11) is overexpressed in diverse malignancies.

Methods: In the present study, we aimed to evaluate the potential role of the immunohistochemical expression of SOX11 in 30 serous ovarian carcinomas in association with E-cadherin and vimentin expression as well as with patients' clinicopathological data.

Results: Most of the examined cases showed concurrent expression of E-cadherin and vimentin, whereas SOX11 was expressed in a minority of the cases (26.7%). Interestingly, the positive cases more frequently had a metastatic disease at the time of diagnosis compared with the negative cases (p = 0.09), an association, however, of marginal significance. Moreover, there was a negative correlation between E-cadherin and SOX11 expression (p = 0.0077) and a positive correlation between vimentin and SOX11 expression (p = 0.0130).

Conclusions: The present work, for the first time, provides preliminary evidence of a possible implication of SOX11 overexpression in the promotion of EMT in metastatic serous ovarian cancer, thereby endorsing tumor metastasis.

Keywords: E-cadherin; SOX11; cancer; epithelial–mesenchymal; ovarian; transition.

Figure 1

E-cadherin, SOX11, and vimentin expression in ovarian serous carcinomas. (A–C) A high-grade serous carcinoma with metastatic disease at diagnosis: (A) expression of E-cadherin in the majority of the tumor cells (insert shows some negative tumor cells), ×200; (B) partial expression of vimentin, ×200; (C) nuclear expression of SOX11 in the majority of the tumor cells (insert shows higher magnification of positive immunoreactivity), ×200. (D–F) A high-grade serous carcinoma with metastatic disease at diagnosis: (D) absence of E-cadherin immunopositivity (insert shows one single positive tumor cell, which also serves as internal positive control), ×200; (E) overexpression of vimentin (insert shows positive membranous immunoreactivity in tumor cells); (F) increased expression of SOX11 (insert shows some positive and some negative nuclei) ×200. (G–I) A low-grade serous carcinoma without metastatic disease at diagnosis: (G) positive expression of E-cadherin in all tumor cells; (H) negative expression of vimentin in all tumor cells (insert shows the negative in higher magnification), ×200; (I) absence of SOX11 immunopositivity (insert shows negative nuclei) ×200.

Figure 2

Schematic representation of the association between E-cadherin expression and presence of metastasis. A significantly higher E-cadherin expression is observed in serous ovarian carcinoma without metastatic disease compared with the ones with a metastatic disease at the time of diagnosis (Mann–Whitney U test, p = 0.0063).

Figure 3

Schematic representation of the association between SOX11 positivity and the presence of metastasis. Red represents SOX11-positive cases, and blue represents SOX11-negative cases. A higher proportion of positive SOX11 expression is observed within the group of serous ovarian carcinomas with a metastatic disease at the time of diagnosis compared with cases without metastasis. This association was statistically of borderline significance (chi-square test, p = 0.09).