Pluripotent stem cell marker deficiency in salivary mucoepidermoid carcinoma with relevance to molecular profiling: An experimental study.

Abstract

Aim: Salivary gland mucoepidermoid carcinoma (MEC) is a morphologically challenging tumor, harboring a canonical CRTC1/3:MAML2 fusion, if investigated. However, the large cohorts available did not invesitgate the diagnosed cases adequately; leaving any mucin-producing malignancy possible MECs although >50% of salivary gland tumors secret mucin luminally or extra-luminally. This study examined the expression of stem cell markers Nanog, SOX2, OCT4, and MENA in salivary MEC using immunohistochemistry and to confer, whether or not, they may have a potential role in defining the tumoral molecular profile.

Materials and methods: Forty well-investigated parotid MEC cases (p63+, p40+, CK7+, Ck5/6+, AE1/AE3+, EMA+, S100 -, ATF1 -, WT1-, SOX9 - and SOX10 -), all with MAML2 rearrangements and without EWSR1 alteration, were interrogated using immunohistochemical techniques to detect the immunoreactivity for Nanog, SOX2, OCT4, and MENA. Additionally, the POU5F1 FISH probe was used to confirm the immunohistochemical findings for OCT4.

Results: Immunohistochemical analysis revealed negative or nonspecific immunoreactivity of NANOG, SOX2, and OCT4 antibodies throughout all examined specimens, inferring deficient pluripotency factor within MEC cellular oncogenesis. However, MENA was widely expressed in all cases. The results of the POU5 F1 FISH probe were consistent with the immunohistochemical data, showing no detectable expression of OCT4, Nanog or SOX2, across all 40 samples.

Conclusion: Cancer stem cells likely do not play any significant role in the pathogenesis of salivary MEC. The widespread expression of MENA, however, suggests that it has functions beyond promoting stemness or pluripotency in these tumors.