Expression of MRP1 and ABCG2 is associated with adverse clinical outcomes of papillary thyroid carcinoma with a solid component

Abstract

Solid variant of papillary thyroid carcinoma (PTC) is characterized by a solid component (SC) retaining classical cytological features of PTC. Despite some controversies, PTC with SC (PTCSC) cases have poor prognosis compared with well-differentiated PTC. We investigated if cancer stem cells (CSCs) may have a role in pathogenesis of PTCSC. PTCSC tumors (n=27) were histologically represented by a mixture of papillary component (PC) and varying degrees of SC involving 10% to 85% of the tumor. Immunohistochemical expression of CSC markers ABCG2 and MRP1, and HBME1 and CK19 was compared between SC and PC within each tumor in association with clinicopathological parameters. ABCG2 and MRP1 were highly expressed in SC, whereas their expression was limited or absent in PC (P=.04 and .002, respectively). In contrast, expression of HBME1 and CK19 appeared higher in PC than in SC (P=.08 and .02, respectively). Higher expression of ABCG2 was associated with higher incidence of large-sized SC (P=.01). Higher expression of MRP1 was associated with higher incidence of lymphovascular invasion (P=.049). Higher expression of ABCG2 and MRP1, and lower expression of CK19 in SC were associated with higher tumor recurrence rate (P=.02, .01, and .02, respectively), and shorter disease-free survival (P<.001 for all the variables). Our findings indicate that the tumor cells harboring CSC-like characteristics in SC could contribute to the pathogenesis of PTCSC and might account for the poor disease prognosis.