演題番号 : P91-1
Uterine carcinosarcoma (CS) is a highly malignant neoplasm known in connection with poor prognosis. Prognostic factors as well as solid therapeutic procedures have not been established, therefore novel therapeutic target must urgently be developed. We reported that Imp3 confers malignant phenotype and tumorigenesis in vitro and in vivo using mouse sarcoma model (Ueki et al, PlosOne, 2012). IMP3 is considered as an oncofetal protein and suggested as a prognostic marker in various human malignancies. Here we investigated IMP3 expression in human CS and correlation with the clinical outcome. Furthermore, we tried to clarify molecular functions of IMP3.
Tumor specimens from 21 patients with CS in Keio University Hospital were used for the study with informed concent. We evaluated the expression and clinicopathologic significance of IMP3 based on immunohistochemical analyses. Our previous study with epigenetic modifiers such as DNMT1 or HDAC inhibitor revealed that the up-regulation of Imp3 was at least partially attributable to epigenetic regulation. We further evaluated epigenetic histone modification in CS, and analyzed correlation between IMP3 expression and the clinical outcome.
There was significant correlation between IMP3 expression and overall survival in CS (p<0.05). Carcinomatous components in CS were related to the clinical outcome, while sarcomatous components did not. Histone modification status was correlated to the IMP3 expression and considered as an independent prognostic factor in CS (p<0.05). These findings suggested that IMP3 expression correlates to histone modification in CS.
IMP3 expression might be a new prognostic factor in uterine CS. IMP3 is expected as a novel cancer-specific therapeutic target to CS as an oncofetal protein. In addition, IMP3 confers epigenetic histone modification. To clarify further mechanical regulation on IMP3 leads to the establishment of new therapeutic strategies to CS.