Role of phospho–ezrin in differentiating thyroid carcinoma

Comprehensive theory explaining the relationship between estrogen (E2) and ezrin in metastasis of thyroid cancer remains non-elicited. In vitro results revealed that E2 could stimulate the expression and phosphorylation of ezrin in a time and dose dependent manner. Our data clearly showed that E2 enhanced the migration and invasion of cells, which was reversed by the transfection of cells with ezrin specific siRNA. Further, we observed that Phosphoinositide 3-kinase (PI3K) ROCK-2 are among the kinases responsible for E2 induced phosphorylation of ezrin. Clinical validation of ezrin/phospho-ezrin revealed that phospho-ezrin was intensely expressed in follicular thyroid carcinoma (FTC) and follicular variant of papillary thyroid carcinoma (FVPTC), while it was completely absent in follicular adenoma (FA) lesions in which the differentiation of the follicular neoplasms remains subtle. When histology of different carcinomas is correlated with benign FA with respect to phospho-ezrin, we observed that the marker was highly significant (p = 0.0001). 100% sensitivity, specificity and diagnostic accuracy of the above marker in the histological association of FTC, FVPTC with FA, enables us to suggest phospho-ezrin as a diagnostic marker to differentiate the follicular neoplasms. These data are the first to suggest the dynamic regulation of ezrin phosphorylation during metastasis in FTC.