ID1 upregulation and FoxO3a downregulation by Epstein-Barr virus-encoded LMP1 in Hodgkin's lymphoma

Cancer-initiating cells (CICs) are specialized cells that have the ability to self-renew and are multipotent. We recently demonstrated that Forkhead box O3a (FoxO3a)-expressing cells exhibited a CIC-like potential in Hodgkin's lymphoma (HL). A proportion of HL patients are infected with Epstein-Barr virus (EBV). EBV-encoded latent membrane protein (LMP) 1 downregulates FoxO3a, suggesting that FoxO3a expression may be abolished in EBV-positive HL. Inhibitors of DNA-binding (ID) proteins are highly conserved transcription factors mediating stem cell functions. To the best of our knowledge, no study has investigated possible associations among ID1, FoxO3a and LMP1 expression in HL to date. We immunohistochemically evaluated the expression of the three abovementioned factors in HL patients. The ID1 expression level was inversely correlated with that of FoxO3a (P=0.00035). LMP1-positive HL cells abundantly expressed ID1 (P=0.029), but not FoxO3a (P=0.00085). Thus, our previous observation that FoxO3a may serve as a marker of CICs may not be applicable in EBV-positive HL patients, but rather ID1 may be a candidate CIC marker in this type of HL.