Search

5591 Background: The benefit of cytoreductive surgery for uterine carcinosarcoma (CS) is unknown. The objective of this study was to assess the impact of optimal debulking surgery on survival of ad...

The mechanisms of the increase in the percentage of alpha-fetoproteins (AFPs) that strongly binds to Lens culinaris agglutinin (AFP-L3) in pregnancies with a trisomy 21 fetus have not been analyzed. To investigate the oligosaccharide variants of AFP produced by normal fetuses and fetuses with trisomy 21, the lectin reactivity of AFP was analyzed.Fetal liver tissue, amniotic fluid, and maternal serum were obtained from five normal pregnancies and five pregnancies with a trisomy 21 fetus. The percentages of AFP reactive to lectins were determined by lectin-affinity electrophoresis coupled with antibody-affinity blotting.The percentages of AFP-L3 in the fetal liver and the maternal serum were 23.9 and 27.0%, respectively, in normal pregnancies, and 28.7 and 38.5%, respectively, in pregnancies with a trisomy 21 fetus. There was no statistically significant difference between the percentage in the fetal liver and the percentage in the maternal serum in normal pregnancies; however, a significant difference (P0.01) was found in pregnancies with a trisomy 21 fetus. In regard to the percentage of AFP-L3 in the fetal liver, there was no significant difference; however, a significant difference (P0.05) was found in the maternal serum between normal pregnancies and pregnancies with a trisomy 21 fetus.The transference of the AFP-L3 fraction might be relatively high in the placentas of women carrying a trisomy 21 fetus, and this could be the one of the reasons for the increase in the percentage of AFP-L3 in the maternal serum in pregnancies with a trisomy 21 fetus.

We report the first case of an intrauterine treatment for cystic hygroma. Guided by ultrasonography, we first removed intracystic fluid from two cysts and then injected OK-432 into each fetal cyst at 21 and 28 weeks of gestation. No re-enlargement of the cysts was subsequently observed. At 38 weeks of gestation, a male infant was delivered transvaginally. Only a slight skin fold was observed in the nuchal area of the neonate, indicating the effectiveness of OK-432 for the intrauterine treatment of cystic hygroma.

Objective. The aim of this study was to determine pathologic variables associated with disease-specific survival of node-positive patients with endometrial carcinoma treated with combination of surgery including pelvic and para-aortic lymphadenectomy and adjuvant chemotherapy. Methods. Survival of 55 node-positive endometrial carcinoma patients prospectively treated with surgery and adjuvant chemotherapy between 1982 and 2002 at Hokkaido University Hospital was compared to various histopathologic variables. All patients underwent primary surgical treatment including pelvic and para-aortic lymphadenectomy followed by adjuvant chemotherapy consisting of intravenous cisplatin, doxorubicin, and cyclophosphamide. Survival analyses were performed by the Kaplan–Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis using a forward stepwise selection. Results. Among 303 consecutive endometrial cancer patients treated during the period of this study, 55 patients (18.2%), including 44 without peritoneal metastasis (FIGO stage IIIc) and 11 with peritoneal metastasis (FIGO stage IV), were found to have retroperitoneal lymph node metastasis. Multivariate Cox regression analysis revealed that peritoneal metastasis and lymph-vascular space invasion (LVSI) were independently related to poor survival in node-positive endometrial carcinoma. The estimated 5-year survival rate of stage IIIc patients with or without moderate/prominent LVSI was 50.9% and 93.3%, respectively with statistically significant difference ( P = 0.0024). The estimated 5-year survival rate of stage IV patients was 20.0%. Prognosis of stage IIIc patients could be stratified into three groups by the number of positive para-aortic node (PAN) with an estimated 5-year survival rate of 86.4% for no positive PAN ( n = 23), 60.4% for one positive PAN ( n = 13), and 20.0% for ≥ 2 positive PAN ( n = 8). The difference of survival rate between no or one positive PAN and ≥ 2 positive PAN was statistically significant ( P = 0.0007 for no positive PAN vs ≥ 2 positive PAN, P = 0.0319 for one positive PAN vs ≥ 2 positive PAN). Multivariate analysis including number of positive PAN groups showed that LVSI, number of positive PAN groups were independent prognostic factors for survival. Survival of patients with stage IIIc disease could be stratified into three groups by combination of LVSI and number of positive PAN groups with an estimated 5-year survival rate of 93.3% for no or one positive PAN group with nil or minimal LVSI, 62.6% for no or one positive PAN group with intermediate or prominent LVSI, and 20.0% for ≥ 2 positive PAN groups irrespective of LVSI ( P = 0.0002 for no or one positive PAN group with nil or minimal LVSI vs ≥ 2 positive PAN groups, P = 0.0223 for no or one positive PAN group with nil or minimal LVSI vs no or one positive PAN group with intermediate or prominent LVSI, P = 0.0388 for no or one positive PAN group with intermediate or prominent LVSI vs ≥ 2 positive PAN groups). Conclusions. LVSI and number of positive PAN groups were independent prognostic factors for stage IIIc endometrial cancer patients. Postoperative therapy and follow-up modality need to be individualized according to LVSI and the number of positive PAN for stage IIIc patients. New molecular markers to predict the prognosis of endometrial cancer patients preoperatively should be found for individualization of treatment. New chemotherapy regimen including taxane needs to be considered as an adjuvant therapy for patients with node-positive endometrial cancer.

The feasibility and accuracy of high dose three-dimensional conformal boost (3DCB) using three internal fiducial markers and a two-orthogonal X-ray set-up of the real-time tumor-tracking system on patients with gynecological malignacy were investigated in 10 patients. The standard deviation of the distribution of systematic deviations (Sigma) was reduced from 3.8, 4.6, and 4.9 mm in the manual set-up to 2.3, 2.3 and 2.7 mm in the set-up using the internal markers. The average standard deviation of the distribution of random deviations (sigma) was reduced from 3.7, 5.0, and 4.5 mm in the manual set-up to 3.3, 3.0, and 4.2 mm in the marker set-up. The appropriate PTV margin was estimated to be 10.2, 12.8, and 12.9 mm in the manual set-up and 6.9, 6.7, and 8.3 mm in the gold marker set-up, respectively, using the formula 2Sigma + 0.7sigma. Set-up of the patients with three markers and two fluoroscopy is useful to reduce PTV margin and perform 3DCB.

It is generally believed that the lower the grade of differentiation of glycoprotein-producing cells, the more often modification by bisecting N-acetylglucosamine (GlcNAc) or fucose (Fuc) at the sugar chain of the glycoprotein or increase in branching of side chains occurs. We examined the characteristics of the alpha-fetoprotein (AFP) sugar chain stored in amniotic and exocoelomic fluid during 5-9 weeks of gestation and analyzed serum-derived AFP of patients with germ cell tumors.Total AFP concentrations in embryonic fluid at 5-9 weeks of gestation (n = 11) and serum of patients with germ cell tumors (n = 7) were measured using a radioimmunoassay (RIA) method. The percentages of AFPs reactive with Lens culinaris agglutinin (LCA), concanavalin A (Con A), erythroagglutinating phytohemagglutinin-E4 (E-PHA) and Ricinus communis agglutinin-120 (RCA 120) were obtained by lectin-affinity electrophoresis coupled with antibody-affinity blotting.It was revealed that at 5-9 weeks of gestation, AFP variants that had been modified by the Fuc residue, which bound to the GlcNAc residue at the reducing end of the sugar chain, and bisecting GlcNAc residues gradually decreased as pregnancy advanced; however, the presence of N-acetylneuraminic acid (Neu5Ac) at the nonreducing ends changed little.It appears very likely that the changes in the relative amounts of AFP variants in the embryonic fluid during early pregnancy were due to differentiation of the yolk sac. The grade of differentiation of yolk sac tumors was very similar to that of the normal yolk sac at around 6 weeks of gestation.

We examined the effect of lipopolysaccharide (LPS), a component of the outer wall of gram-negative bacteria, on expression of the neutrophil chemoattractant interleukin-8 (IL-8) and the effects of IL-8 treatment on release of matrix metabolizing enzymes in human cervical smooth muscle cells (CSMCs). Human CSMCs were exposed to Escherichia coli LPS, and the expression of IL-8 mRNA was analyzed by Northern blotting. The Il-8 promoter activity was examined by dual luciferase assay, and the IL-8 concentration was assessed by enzyme-linked immunosorbent assay. We also treated the CSMCs with human IL-8 and examined the expression of matrix-degrading enzymes. E coli LPS (100 ng/mL) increased the expression of IL-8 mRNA 12.8-fold after 3 hours. This up-regulation was maintained for up to 24 hours. Lipopolysaccharide treatment produced a fivefold increase in IL-8 promoter activity in CSMCs transfected with an Il-8 promoter-reporter construct. IL-8 concentrations in conditioned medium of CSMC cultures treated with E coli LPS increased approximately 18-fold compared with the control culture. Northern blot analysis and zymography revealed that exogenous human IL-8 had no significant effect on the expression of matrix metalloproteinase (MMP)-1, -3, and tissue inhibitor of metalloproteinase (TIMP)-1 mRNAs, and on the secretion MMP-2 and -9 in CSMCs. We conclude that CSMCs respond to LPS with increased expression of IL-8 mRNA and secreted IL-8, and that expression of matrix metabolizing enzymes in CSMCs is not directly affected by IL-8. IL-8 produced by CSMCs in reponse to gram-negative infection may promote neutrophil invasion, and release of neutrophil matrix-degrading enzymes may participate in the matrix remodeling associated with parturition.

Cholesterol is an important structural component of membranes as well as a precursor for steroid hormone, bile acid and regulatory oxysterol biosynthesis. Recent observations revealed that cholesterol plays an important role in signaling and the regulation of intracellular vesicular trafficking. Studies on Niemann–Pick type C disease, a fatal neuro-visceral cholesterol storage disorder, led to the elucidation of a sterol-modulated vesicular trafficking pathway. Mutations in the NPC1 gene, which cause the majority of cases of Niemann–Pick type C disease, result in the accumulation of free cholesterol in lysosomes and associated defects in glycolipid sorting. NPC1 has a sterol-sensing domain that presumably recognizes free sterols in the protein’s environment and participates in the movement of cholesterol out of lysosomes. The compartment containing NPC1 is a subset of late endosomes; it is highly mobile, travels along microtubules, emitting flexible tubules. The movements of this compartment require an intact NPC1 sterol-sensing domain and are dramatically suppressed when free cholesterol accumulates in the late endosomes. Two other proteins involved in sterol trafficking enter into the NPC1 compartment, NPC2 also known as HE1, a secreted sterol-binding glycoprotein, and MLN64, a StAR-related lipid transfer (START) domain protein, which can bind cholesterol and promote its movement from donor to acceptor membranes. Mutations in NPC2 cause a rarer form of Niemann–Pick type C disease, establishing its importance in intracellular sterol movement. NPC2, NPC1 and MLN64 may act in an ordered sequence to sense cholesterol, effect sterol movement, and consequently, influence the process of vesicular trafficking.

Steroid hormones produced in the adrenals, gonads, and placenta are important regulators of tissue differentiation, development, and homeostasis. The first committed step in the synthesis of these hormones in all tissue types is the conversion of cholesterol into pregnenolone. This reaction is catalyzed by the cytochrome P450 side-chain cleavage enzyme (P450 scc ), located on the matrix side of the inner mitochondrial membrane. This first step in steroidogenesis, which is highly regulated in a temporal and tissue-specific manner, is primarily controlled at the level of cholesterol availability to the inner-mitochondrial matrix rather than at the level of P450 scc enzyme activity. It has been known for decades that the acute regulation of steroid-hormone synthesis in the adrenals and gonads is dependent upon the synthesis of a protein(s) in response to trophic hormones and that this protein is fast-acting (minutes) and functionally short-lived. The recently cloned Steroidogenic Acute Regulatory (StAR) protein appears to be the “labile protein” essential for the acute steroidogenic response. Absence of functional StAR protein causes congenital lipoid adrenal hyperplasia (lipoid CAH), a disease characterized by marked impairment of adrenal and gonadal steroid hormone synthesis. Recent data implicate cAMP-mediated pathways in the regulation of StAR mRNA expression via a mechanism that depends upon the orphan nuclear hormone receptor, steroidogenic factor-1 (SF-1). Additional data suggest that cAMP-mediated pathways stimulate StAR function at the posttranslational level by initiating protein kinase A (PKA)-mediated phosphorylation of StAR. Although StAR has been shown to be imported and processed by mitochondria, this event is not essential to StAR function. It appears that StAR acts on the outer mitochondrial membrane, stimulating sterol desorption from the sterol-rich outer membrane and its transfer to the relatively sterol-poor inner membrane.

The Niemann-Pick C1 (NPC1) protein and endocytosed low density lipoprotein (LDL)-derived cholesterol were shown to enrich separate subsets of vesicles containing lysosomal associated membrane protein 2. Localization of Rab7 in the NPC1-containing vesicles and enrichment of lysosomal hydrolases in the cholesterol-containing vesicles confirmed that these organelles were late endosomes and lysosomes, respectively. Lysobisphosphatidic acid, a lipid marker of the late endosomal pathway, was found in the cholesterol-enriched lysosomes. Recruitment of NPC1 to Rab7 compartments was stimulated by cellular uptake of cholesterol. The NPC1 compartment was shown to be enriched in glycolipids, and internalization of GalNAcbeta1-4[NeuAcalpha2-3]Galbeta1-4Glcbeta1-1'-ceramide (G(M2)) into endocytic vesicles depends on the presence of NPC1 protein. The glycolipid profiles of the NPC1 compartment could be modulated by LDL uptake and accumulation of lysosomal cholesterol. Expression in cells of biologically active NPC1 protein fused to green fluorescent protein revealed rapidly moving and flexible tubular extensions emanating from the NPC1-containing vesicles. We conclude that the NPC1 compartment is a dynamic, sterol-modulated sorting organelle involved in the trafficking of plasma membrane-derived glycolipids as well as plasma membrane and endocytosed LDL cholesterol.

Introduction: This is the second report on the conservative treatment of endometrial carcinoma in a female patient younger than fifteen years. Case A, a 14-year-old teenager, presented with menorrhagia. An endometrial biopsy revealed grade 2 endometrioid adenocarcinoma. The estrogen receptor and progesterone receptor were strongly positive in 60% and 90% of the tumor, respectively. Although she was administered medroxyprogesterone acetate for a month, it was not effective. She underwent standard surgery including a hysterectomy. She was thereafter free of disease 1 year after surgery. No estrogen receptor staining of the surgical specimen was observed, and 30% of the tumor was strongly positive for progesterone receptor. Direct DNA sequencing of exons 7 and 8 of PTEN and the K-ras codon 12 demonstrated the presence of no mutation. In addition, no dominant-negative p53 mutation was found by a yeast functional assay. Conclusion: A uterine malignancy should therefore be included in the differential diagnosis in a young female patient complaining of abnormal genital bleeding.

There have so far only been few reports on the intrathoracic injection (IT) of paclitaxel for ovarian cancer.The patient was treated with IT paclitaxel to control a large volume of pleural effusion as neoadjuvant chemotherapy. A total of 220 mg (110 mg in each thoracic cavity) of paclitaxel was administrated and the pleural effusion dramatically decreased. The intrathoracic concentration of paclitaxel was 1,524.0, 107.5, 8.1, 11.0 and 3.8 microm/l at 0, 24, 48, 72 and 96 h, respectively. The plasma concentration was 0.05, 0.11, 0.07, 0.04 and 0.02 microm/l, respectively.An extremely high concentration was maintained over 96 h and there was slight transition into general circulation following IT administration. IT paclitaxel might be effective in some patients with ovarian serous adenocarcinoma who have a refractory tumor in the thoracic cavity.

Niemann-Pick type C (NPC) disease, characterized by accumulation of low density lipoprotein-derived free cholesterol in lysosomes, is caused by mutations in the NPC1 gene. We examined the ability of wild-type NPC1 and NPC1 mutants to correct the NPC sterol trafficking defect and their subcellular localization in CT60 cells. Cells transfected with wild-type NPC1 expressed 170- and 190-kDa proteins. Tunicamycin treatment resulted in a 140-kDa protein, the deduced size of NPC1, suggesting that NPC1 is N-glycosylated. Mutation of all four asparagines in potential N-terminal N-glycosylation sites to glutamines resulted in a 20-kDa reduction of the expressed protein. Proteins with a single N-glycosylation site mutation localized to late endosome/lysosomal compartments, as did wild-type NPC1, and each corrected the cholesterol trafficking defect. However, mutation of all four potential N-glycosylation sites reduced ability to correct the NPC phenotype commensurate with reduced expression of the protein. Mutations in the putative sterol-sensing domain resulted in inactive proteins targeted to lysosomal membranes encircling cholesterol-laden cores. N-terminal leucine zipper motif mutants could not correct the NPC defect, although they accumulated in lysosomal membranes. We conclude that NPC1 is a glycoprotein that must have an intact sterol-sensing domain and leucine zipper motif for cholesterol-mobilizing activity.

Ovarian cancer is one of the most aggressive female reproductive tract tumors. Paclitaxel (PTX) is widely used for the treatment of ovarian cancer. However, ovarian cancers often acquire chemotherapeutic resistance to this agent. We investigated the mechanism of chemoresistance by analysis of microRNAs using the ovarian cancer cell line KFr13 and its PTX-resistant derivative (KFr13Tx). We found that miR-31 was downregulated in KFr13Tx cells, and that re-introduction of miR31 re-sensitized them to PTX both in vitro and in vivo. miR-31 was found to bind to the 3′-UTR of mRNA of MET, and the decrease in MET correlated to higher sensitivity to PTX. Furthermore, co-treatment of KFr13Tx cells with MET inhibitors sensitized the tumor cells to PTX both in vitro and in vivo. In addition, lower levels of miR31 and higher expression of MET in human ovarian cancer specimens were significantly correlated with PTX chemoresistance and poor prognosis. This study demonstrated miR31-dependent regulation of MET for chemoresistance of ovarian cancer, raising the possibility that combination therapy with a MET inhibitor and PTX will increase PTX efficacy.

Objective: The aim of this study was to investigate the prognostic factors and treatment outcome of patients with adeno car cinoma of the uterine cervix who underwent radical hysterectomy with systematic lymphadenectomy. Methods: A total of 130 patients with stage IB to IIB cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy from 1982 to 2005 were retrospectively analyzed. Clinicopathological data including age, stage, tumor size, the number of positive node sites, lymphovascular space invasion, parametrial invasion, deep stromal invasion (>2/3 thickness), corpus invasion, vaginal infiltration, and ovarian metastasis, adjuvant therapy, and survival were collected and Cox regression analysis was used to determine independent prognostic factors. Results: An estimated five-year survival rate of stage IB1 was 96.6%, 75.0% in stage IB2, 100% in stage IIA, and 52.8% in stage IIB. Prognosis of patients with one positive-node site is similar to that of those with negative-node. Prognosis of patients with multiple positive-node sites was significantly poorer than that of negative and one positive-node site. Multivariate analysis revealed that lymph node metastasis, lymphovascular space invasion, and parametrial invasion were independent prognostic factors for cervical adenocarcinoma. Survival of patients with cervical adenocarcinoma was stratified into three groups by the combination of three independent prognostic factors. Conclusion: Lymph node metastasis, lymphovascular space invasion, and parametrial invasion were shown to be independent prognostic factors for cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy.

Background Clusterin is a cytoprotective chaperone protein involved in numerous physiological processes, carcinogenesis, tumor growth and tissue remodelling. The purpose of this study was to investigate whether clusterin (CLU), an antiapoptotic molecule, could be a potential predictor molecule for ovarian cancer and whether or not targeting this molecule can improve survival of ovarian cancer patients. Methods Clusterin expression was compared between ten primary and their recurrent tumors from same patients immunohistochemically. We analyzed prognostic significance of CLU expression in another 47 ovarian cancer tissue samples by immunohistochemistry. We used small interference RNA to knock down CLU in the chemo-resistant ovarian cancer cell lines. KF-TX and SKOV-3-TX, paclitaxel-resistant ovarian cancer cells, were established from parental KF and SKOV-3 chemo-sensitive cell lines, respectively. Either siRNA or second generation antisense oligodeoxynucleotide against CLU (OGX-011), which is currently evaluated in clinical phase II trials in other cancer s, was used to modulate sensitivity to paclitaxel (TX) in ovarian cancer cells in vitro. Cellular viability assay, FACS analysis and annexin V staining were used to evaluate the comparative effect of CLU knocking down in ovarian cancer cells. Results Immunohistochemical analysis of CLU expression in primary ovarian cancer tissue specimens and their recurrent counterparts from same patients demonstrated higher expression of CLU in the recurrent resistant tumors compared with their primary tumors. High expression of CLU by immunohistochemistry among 47 surgical tissue specimens of early-stage (stage I/II) ovarian cancer, who underwent complete cytoreduction as a primary surgery, significantly related to poor survival, while none of other clinicopathological factors analyzed were related to survival in this patient cohort. Secretory CLU (s-CLU; 60 KDa) expression was upregulated in TX-resistant ovarian cancer cells compared to parental cells. Transfection of siRNA or OGX-011 clearly reduced CLU expression. Cell viability assay, FACS analysis and annexin V staining demonstrated that targeting CLU expression by siRNA or OGX-011 sensitized ovarian cancer cells to TX. Conclusion We conclude that CLU could be a potential molecular target to predict survival while targeting this s-CLU may improve survival of patients with ovarian cancer.

Background Epithelial-mesenchymal transition (EMT) is the key process driving cancer metastasis. Oncogene/self renewal factor BMI-1 has been shown to induce EMT in cancer cells. Recent studies have implied that noncoding microRNAs (miRNAs) act as crucial modulators for EMT. The aims of this study was to determine the roles of BMI-1 in inducing EMT of endometrial cancer (EC) cells and the possible role of miRNA in controlling BMI-1 expression. Methods and results We evaluated the expression of BMI-1 gene in a panel of EC cell lines, and detected a strong association with invasive capability. Stable silencing of BMI-1 in invasive mesenchymal-type EC cells up-regulated the epithelial marker E-cadherin, down-regulated mesenchymal marker Vimentin, and significantly reduced cell invasion in vitro. Furthermore, we discovered that the expression of BMI-1 was suppressed by miR-194 via direct binding to the BMI-1 3'-untranslated region 3'-UTR). Ectopic expression of miR-194 in EC cells induced a mesenchymal to epithelial transition (MET) by restoring E-cadherin, reducing Vimentin expression, and inhibiting cell invasion in vitro. Moreover, BMI-1 knockdown inhibited in vitro EC cell proliferation and clone growth, correlated with either increased p16 expression or decreased expression of stem cell and chemoresistance markers (SOX-2, KLF4 and MRP-1). Conclusion These findings demonstrate the novel mechanism for BMI-1 in contributing to EC cell invasion and that repression of BMI-1 by miR-194 could have a therapeutic potential to suppress EC metastasis.

5100 Background: To predict possibility of lymph node metastasis using primary cancer tissue preoperatively, we explored putative biomarker genes of node metastasis in patients with endometrial can...

Objective Few studies on the prognosticators of the patients with recurrent endometrial cancer after relapse have been reported in the literature. The aim of this study was to determine the prognosticators after relapse in patients with recurrent endometrial cancer who underwent primary complete cytoreductive surgery and adjuvant chemotherapy. Methods Thirty-five patients with recurrent endometrial cancer were included in this retrospective analysis. The prognostic significance of several clinicopathological factors including histologic type, risk for recurrence, time to relapse after primary surgery, number of relapse sites, site of relapse, treatment modality, and complete resection of recurrent tumors were evaluated. Survival analyses were performed by Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Results Among the clinicopathological factors analyzed, histologic type (p=0.04), time to relapse after primary surgery (p=0.03), and the number of relapse sites (p=0.03) were significantly related to survival after relapse. Multivariate analysis revealed that time to relapse after primary surgery (hazard ratio, 6.8; p=0.004) and the number of relapse sites (hazard ratio, 11.1; p=0.002) were independent prognostic factors for survival after relapse. Survival after relapse could be stratified into three groups by the combination of two independent prognostic factors. Conclusion We conclude that time to relapse after primary surgery, and the number of relapse sites were independent prognostic factors for survival after relapse in patients with recurrent endometrial cancer.

5040 Background: The present standard treatment for cases with endometrial cancer is surgical staging including lymphadenectomy. Elimination of lymphadenectomy will not be approved of unless strict condition are met. Our aim is to verify whether a preoperative scoring system to estimate the risk of lymph node metastasis (LNM) in endometrial carcinoma is clinically useful for tailoring the indication of lymphadenectomy. Methods: This study was carried out on 211 patients with endometrial carcinoma for whom volume index, serum CA125 level, tumor grade/histology were preoperatively confirmed. LNM score was set up using these three risk factors as reported in our previous study (Am J Obstet Gynecol 2003). We analyzed whether these factors remain still valid in a different cohort of patients. Based on the LNM score before a validation study was started, the estimated rate of lymph node metastasis (para-aortic lymph node metastasis) in a low risk group was 3.4% (0.0%), an intermediate group 7.7% (5.8%), a high risk group 44.4% (30.6%) and an extremely high risk group 70.0% (50.0%). Results: Volume index, serum CA125 level, and tumor grade/histology, were found to be independent risk factors for LNM in the cohort of this validation study. The actual rate of lymph node metastasis (para-aortic lymph node metastasis) in a low risk group was 3.2% (1.0%), an intermediate group 15.3% (11.9%), a high risk group 30.2% (23.8%) and an extremely high risk group 78.6% (57.1%). Conclusions: LNM frequencies increased in proportion to the impact of the LNM score and the actual rate of lymph node metastasis for each score was quite consistent with the estimated rate of lymph node metastasis.Our LNM score for patients with endometrial carcinoma is useful. No significant financial relationships to disclose.

5160 Background: Standard chemotherapy regimen for recurrent ovarian cancer has not been established. Weekly paclitaxel (PTX) has been reported to be effective for recurrent ovarian cancer. In brea...

5124 Background: Recurrence is a major problem for ovarian cancer patients during follow up. We evaluated the clinical contribution of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) ...

Background: We aimed to investigate whether MIR31 is an oncogene in human endometrial cancer and identify the target molecules associated with the malignant phenotype. Methods: We investigated the growth potentials of MIR31-overexpressing HEC-50B cells in vitro and in vivo. In order to identify the target molecule of MIR31, a luciferase reporter assay was performed, and the corresponding downstream signaling pathway was examined using immunohistochemistry of human endometrial cancer tissues. We also investigated the MIR31 expression in 34 patients according to the postoperative risk of recurrence. Results: The overexpression of MIR31 significantly promoted anchorage-independent growth in vitro and significantly increased the tumor forming potential in vivo. MIR31 significantly suppressed the luciferase activity of mRNA combined with the LATS2 3'-UTR and consequently promoted the translocation of YAP1, a key molecule in the Hippo pathway, into the nucleus. Meanwhile, the nuclear localization of YAP1 increased the transcription of CCND1. Furthermore, the expression levels of MIR31 were significantly increased (10.7-fold) in the patients (n = 27) with a high risk of recurrence compared to that observed in the low-risk patients (n = 7), and this higher expression correlated with a poor survival. Conclusions: MIR31 functions as an oncogene in endometrial cancer by repressing the Hippo pathway. MIR31 is a potential new molecular marker for predicting the risk of recurrence and prognosis of endometrial cancer.