Different expression profiles of Y‐box‐binding protein‐1 and multidrug resistance‐associated proteins between alveolar and embryonal rhabdomyosarcoma

Nuclear expression of the Y‐box‐binding protein‐1 (YB‐1) has been reported to regulate the expression of both P‐glycoprotein (P‐gp) and major vault protein (MVP), and to regulate proliferative activities in human malignancies. Based on morphology and molecular biology, rhabdomyosarcoma (RMS) can be divided into two major types: embryonal type and the more aggressive alveolar type. Thirty‐five cases of embryonal RMS (ERMS) and 28 cases of alveolar RMS (ARMS) were examined immunohistochemically for the nuclear expression of YB‐1 and the intrinsic expression of P‐gp, multidrug resistance (MDR)‐associated protein (MRP) 1, 2, and 3, breast‐cancer resistant protein (BCRP) and MVP, and the findings were compared with proliferative activities as evaluated by the MIB‐1‐labeling index (LI). Moreover, mRNA levels of these MDR‐related molecules were assessed using a quantitative reverse transcriptase‐PCR method in 18 concordant frozen materials. P‐gp expression was more frequently observed ARMS, compared with ERMS ( P =  0.0332), whereas immunoreactivity for BCRP was more frequently recognized in ERMS ( P =  0.0184). Nuclear expression of YB‐1 protein was correlated with P‐gp ( P =  0.0359) and MVP ( P =  0.0044) expression, and a higher MIB‐1‐labeling index ( P =  0.0244) in ERMS, however, in ARMS no such relationships were observed. These immunohistochemical results indicate that different expression profiles of MDR‐related molecules and their correlation with YB‐1 nuclear expression support the concept that ERMS and ARMS are molecular biologically distinct neoplasms. Apart from ERMS, frequent P‐gp expression in ARMS may be independent from YB‐1 regulation. However, YB‐1 may be a candidate for a molecular target in rhabdomyosarcoma therapy, especially in ERMS. ( Cancer Sci 2008; 99; 726–732)