Thymic epithelial tumours (TET) are classified according to WHO 2015 subtype and Masaoka stage. Ephrins (ephs) and their receptors (EPHs) –members of the receptor tyrosine kinases (RTKs) superfamily- are implicated in tissue development and homeostasis and aberrantly expressed in tumors. Several preclinical studies have reported safety of EPH-targeting factors. In EPH-B-deficient thymi the epithelial network is disrupted, but thymocyte development is spared. Hence, inhibition of EPH-Bs may constitute a strategy against TETs, without producing immune deficits. To our knowledge EPH-B expression has not been previously studied in TETs.
EPH-B1, -B2, -B4 and -B6 immunohistochemistry was examined in 98 TETs, (12 type A, 22 AB, 17 B1, 18 B2, 14 B3, 2 micronodular thymomas and 13 thymic carcinomas) and immunoreactivity scoring system (IRS) was used in clinicopathological correlations. Pearson’s x2 test was applied for association analysis.
EPH-B1 nuclear and cytoplasmic expression pattern was noted in the epithelial compartment of all TET, with variations in their lymphocytic component. EPH-B2 was weakly and focally expressed in the cytoplasm of the epithelial cells and mostly weakly in lymphocytic nuclei in half of the cases. EPH-B6 nuclear expression pattern was variable, more common in lymphocytes, and present in about 2/3 of the tumours. EPH-B4 was not expressed. Lymphocytes in thymomas presented higher EPH-B6 IRS compared to thymic carcinomas (p<.001), where they probably represent antitumoral immune reaction; conversely, lymphocytic EPH-B1 expression was higher in carcinomas (p=0.026). Thymomas of early Masaoka stages presented higher lymphocytic (p=0.043) and lower epithelial (p=0.010) EPH-B6 IRS. Lymphocytic EPH-B1 expression was less strongly correlated with stage (p=0.059).
EPH-B1, -B2 and -B6 are expressed in both the epithelial and lymphocytic component of TETs. The expression level of EPH-B1 and -B6 correlates with established prognostic parameters, i.e. tumour subtype and Masaoka stage, suggesting involvement of these RTKs in thymic neoplasia, as well as their potential utility as therapeutic targets.
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