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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.
( Han Byoul Cho ),( Joon Yong Chung ),( Mikiko Takikita ),( Stephen M Hewitt ),( Jae Hoon Kim ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.98 No.-
The protein kinase B (AKT) pathway plays a key role in the regulation of cell death and survival, and has been proposed as a central signaling event in carcinogenesis. We investigated the expression of MKRN1, which is a transcriptional co-regulator and an E3 ligase, and sought to define the role of AKT pathway in cervical neoplasias. One hundred eighty three cervical cancer, 415 cervical intraepithelial neoplasia, and 400 matched nonadjacent normal tissues were arrayed into tissue microarrays. MKRN1, phosphorylated AKT (pAKT), phosphorylated mammalian target of rapamycin (pmTOR), and total phosphatase and tensin homolog deleted on chromosome 10 (PTEN) protein expressions were assessed by immunohistochemistry (IHC) and the relationship between MKRN1 expression and clinicopathologic parameters including survival data was studied. MKRN1, pAKT, and pmTOR expressions were significantly increased in cervical cancer cases compared with normal epitheliums (p<0.001 for all markers), and this increased expression of MKRN1 was significantly associated with tumor stage (p=0.018) and tumor grade (p<0.001). Expression of MKRN1 was positively associated with pAKT expression (p=0.023), while negatively associated with PTEN expression (p=0.016) in cervical cancer specimens. In multivariate analysis, MKRN1+/pAKT+ (HR = 4.76 [1.66-13.58], p=0.004), pAKT+ (HR = 2.97 [1.02-8.06], p=0.045), and lymph node metastasis (HR = 3.94 [1.07-14.45], p=0.039) were independent prognostic factors for overall survival. This study provides evidence of an association between AKT pathway and cervical carcinogenesis and shows that MKRN1/pAKT expression predicts poor prognosis in cervical cancer. Our findings also suggest that future research assessing its clinical usefulness would be worthwhile.
( Han Byoul Cho ),( Jane Seon Young Kim ),( Hyun Soo Chung ),( Hee Jeong Lee ),( Jae Hoon Kim ) 대한산부인과학회 2012 대한산부인과학회 학술대회 Vol.98 No.-
ARID1A, the tumor suppressor gene, encodes BAF250a which is a component of human SWI/SNF chromatin-remodeling complexes and has recently reported loss of expressions in several tumor types. Here, we investigate the expression levels of the BAF250a during the sequential steps of cervical carcinogenesis and assess its prognostic value. One hundred forty seven cervical cancer patients, 191 cervical intraepithelial neoplasia, and 376 matched nonadjacent normal tissues were arrayed into tissue microarray. BAF250a expressions were assessed by immunohistochemistry (IHC) and studied the relationship between BAF250a expression and clinicopathologic parameters including survival data. The transcriptional level of BAF250a was also evaluated by SYBR Green real-time PCR in 5 cell lines and 10 clinical specimens. We showed that the mRNA expression levels of BAF250a decreased in cervical cancer cell lines (p=0.005) and tissues (p=0.001), compared with normal cervical epithelial tissues, respectively. BAF250a was detected in nuclear factions of HeLa cells and nucleus of cervical cancer tissue sample by western blotting and IHC, respectively. The expression level of BAF250a gradually decreased during the normal to tumor transition of cervical carcinoma (p<0.001), and this loss of the expression was significantly associated with tumor stage (p=0.005), tumor grade (p=0.029), tumor size (p=0.003), and lymph node metastasis (p=0.020). In multivariate analysis, overall survival in cervical cancer was significantly shorter in cases with the loss of BAF250a expression (HR = 2.78 [1.01-7.63], p=0.047). Our results suggest that BAF250a expression has the potential to provide valuable prognostic information to clinicians for risk assessment in cervical cancer.
조한별 ( Han Byoul Cho ),김재훈 ( Jae Hoon Kim ),홍순원 ( Soon Won Hong ),이현준 ( Hyun Joon Lee ),김민경 ( Min Kyoung Kim ),김성훈 ( Sung Hoon Kim ),김영태 ( Young Tae Kim ),김재욱 ( Jae Wook Kim ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.9
Uterine sarcomas are rare tumors of mesodermal origin and constitute 2-6% of uterine malignancies. They are classified into leiomyosarcoma (LMS), malignant mixed mullerian tumors (MMMTs), and endometrial stromal sarcoma (ESS) by histologic types. Endometrial stromal sarcomas account for about 7-15% of uterine sarcomas, about 0.2% of female genital tract malignancies. Endometrial stromal sarcomas are divided into endometrial stromal nodule, low-grade endometrial stromal sarcoma, and high-grade endometrial stromal sarcoma on the basis of mitotic activity and vascular invasion. Clinical outcome of low-grade endometrial sarcoma is better than that of high-grade endometrial stromal sarcoma and has a propensity for slow metastasis. We have experienced a case of low-grade endometrial stromal sarcoma with multiple metastasis in a 41-year-old woman and was treated by surgical resection and combination chemotherapy, which is presented with a review of brief literature.