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- 저자 : ( Till Braunschweig ) (검색결과 1 건)
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( Han Byoul Cho ),( Joon Yong Chung ),( Till Braunschweig ),( Stephen M Hewitt ),( Jae Hoon Kim ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.99 No.-
NKG2D (natural killer group 2, member D) binds to a diverse array of cellular ligands of the MIC and ULBP/RAET family and is thought to participate in anticancer immune response. In this study, we investigated the clinical significance of NKG2D in the pathogenesis of cervical cancer. We assessed the expression of all MICA/B, ULBP1, ULBP2, ULBP3, RAET1E, and RAET1G proteins in archival tumor tissue specimens from 200 cervical cancers, 327 high-grade cervical intraepithelial neoplasias (CINs), 99 low-grade CINs, and 541 matched nonadjacent normal cervical epithelial tissues by immunohistochemical staining. MICA/B, ULBP1, and RAET1E expression were higher in cervical cancer than in low grade CIN (p<0.001, p=0.012, p=0.013, respectively) and normal cervix (all p<0.001). Among these markers, expression of ULBP1 was significantly different in FIGO stage (p=0.010) and tumor size (p=0.045). ULBP1 expression was correlated with MICA/B (p<0.001) and ULBP2 expression (p=0.002) in cervical cancer. MICA/B+ or ULBP1+ showed improved disease-free survival time (p=0.027 and p=0.009, respectively) than low expression group, whereas RAET1E+ or RAET1G+ showed shorter survival time (p=0.018 and p=0.029, respectively). In case of overall survival, ULBP1+ group showed significantly longer survival time (p=0.009). By using multivariate analysis, MICA/B+/ULBP1+ (HR=0.16, p=0.015), ULBP1+ (HR=0.31, p=0.024), tumor stage (HR=3.60, p=0.010), and lymph node metastasis (HR=2.71, p=0.032) were found to be independent predictors of prognosis for disease-free survival in cervical cancer. We demonstrate that MICA/B and ULBP1 expression is significantly increased in cervical cancer, which is consistent with immunoediting mechanism that select selects tumor cells that have lost or reduced expression of NKG2D ligands. Furthermore, the combination of MICA/B and ULBP1 was found to be the independent predictor of survival, suggesting clinical values in clinical assessment.
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