Abstract 1996P
Background
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.
Methods
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.
Results
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).
Conclusions
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.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.