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P756 Expression of nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) on the eutopic endometrium of patients with endometriosis
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Poster presentations / International Journal of Gynecology & Obstetrics 107S2 (2009) S413–S729
P755 Association between endometriosis and haplotype allele of vascular endothelial growth factor K. Jung Gu, P. Kyung Ah, K. Hoon, K. Seung Yup, S. Chang Suk, K. Seok Hyun, C. Young Min, M. Shin Yong. Department of Obstetrics and Gynecology, Seoul National University College of Medicine Objective: To evaluate the association between endometriosis and hapotype allele of vascular endothelial growth factor (VEGF). Materials and Methods: The C(−460)T, C405G and C936T polymorphisms in VEGF gene were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis in 206 women with endometriosis (n = 105) and without endometriosis (n = 101) and their haplotype alleles were analyzed. The serum levels of VEGF were also measured using an enzyme immunoassay. Results: Distributions of C(−460)T, C405G and C936T haplotype alleles were as follow: TCC (36.9%), TGC (22.1%), CGC (20.4%), CGT (10.7%), TCT (6.3%), CCC (1.9%), CCT (1.0%), and TGT (0.7%). Among the haplotype alleles, the frequency of CCC (−460/405/936) haplotype allele was significantly lower in women with endometriosis compared to women without endometriosis (4.0% vs 0.0%, P = 0.01). Serum levels of VEGF in CCC heterozygotes were not different from those in other haplotype genotypes. Conclusion: The CCC haplotype allele of VEGF is one of the genetic factors which may be associated with endometriosis in Korean women. P756 Expression of nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) on the eutopic endometrium of patients with endometriosis S. Seo, B. Lee, S. Cho, H. Kim, Y. Choi, K. Park, D. Cho. Gangnam Severance Hospital Objective: Altered regulation of apoptosis in eutopic endometrium could contribute to survival of endometriotic cell and developed endometriosis. NAG-1, member of transforming growth factor – b (TGF- b) superfamilies, concerns in induction of cell apoptosis. We hypothesized that decreased expression of NAG-1 of eutopic endometrium may be involved in the pathophysiology of endometriosis and investigated the expression of NAG-1 in eutopic endometrium of endometriosis and normal endometrium. Materials and Methods: The relative NAG-1 mRNA expression level of the endometrium was analyzed by real–time RT-PCR in 73 eutopic endometrium (39 from with endometriosis patients and 34 from without endometriosis). Results: NAG-1 mRNA expression of endometrial tissues showed changes through the cycle. That was found decreased as date in proliferative phase (EP, 31.4±23.7, V.S LP, 6.6±6.4, P = 0.000), whereas there was a gradual increase in the secretory phase (ES, 10.3±6.7 V.S LS, 168.2±251.7, P = 0.000). Menstrual and latesecretory phase showed the maximum expression (P = 0.000). When compared NAG-1 mRNA level of each group, during menstrual phase, NAG-1 expressin from endometriosis was significantly lower than the level from women without endometriosis (endometriosis group, 124.7±111.0 V.S control group, 318.0±287.3, P = 0.028). Conclusions: We demonstrated that the presence of NAG-1 in human endometrium and decreased in menstruating eutopic endometrium of endometriosis. Although the role of NAG-1 in human endometriosis is not clear at the present time, it may play a role in the development of endometriois by linked apoptosis.
P757 Investigating novel tumor markers for endometriosis M. Nabeta1 , Y. Abe2 , Y. Kusanagi1 , M. Ito1 , N. Ueda2 . 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, 2 Department of Molecular Pathology, Ehime University Graduate School of Medicine Objectives: Endometriosis, affecting women of reproductive ages, causes pelvic pain and is attributed as the cause of approximately 15% of infertility cases. The diagnosis of endometriosis is traditionally based on laparoscopic visualization; however, this method is worrisome and is not a trivial procedure. Therefore, less invasive methods for the diagnosis of endometriosis have been desired. The purpose of this study was to establish a new diagnostic marker for endometriosis which can be applied more easily on a clinical basis. Material and Methods: Autoantibodies (aAbs) in sera of endometriotic patients and healthy controls were investigated using two-dimensional (2-D) gel electrophoresis, Western blotting and a mesothelial cell line, Meso-1. Proteins at reacted spots were analyzed by MALDI TOF-MS. ELISAs were established by making recombinant proteins and aAbs titers were estimated in sera of endometriotic patients, healthy volunteers and disease control patients. Results: Using 2-D gel electrophoresis and Western blotting, 4 spots were identified as autoantigens specific to endometriosis. These spots were excised from the 2-D gel, and subjected to the MALDI TOF-MS analysis. Proteins A-D were expressed in 2/3–3/3 in Western blotting analysis using patients’ sera. None of these spots were reacted when using healthy volunteers’ sera. After protein identification (Lamin-A/C, Carboxypeptidase O, Aldolase and protein X), recombinant proteins were elaborated. We are currently analyzing these proteins using ELISAs, hoping that they can be applied to the diagnosis of endometriosis. Conclusions: We identified 4 autoantigens for the diagnosis of endometriosis. Further investigation of these proteins is currently underway. P758 A case of ruptured chocolate cyst with extremely high level of serum CA125 and CA19-9 H. Nakachi. Okinawa Syoko Clinic Introduction: A chocolate cyst is one of common benign ovarian tumor due to ovarian endometriosis. Severe abdominal pain complicated with ovarian tumor usually indicates torsion or rupture. The most important clinical implication of CA125 and CA19-9are in the diagnosis and management of ovarian malignancy. I report here a rare case of ruptured benign chocolate cyst complicated severe abdominal pain and fever with extremely high level of serum CA125 and CA19-9. Case report: A 28-year old female 1G1P with ovarian tumor was referred for severe abdominal pain and high fever 38ºC on May 22, 2008. CT reveald cystic tumor on her left adnexa and severe abdominal rebound tenderness was seen. Her clinical signs and symptoms indicate peritonitis. IV antibiotic therapy was started. One day after admission, her abdominal pain and fever disappeared. Her serum CA125 and CA19-9were 6947.1 U/ml, 3647.9 U/ml, respectively. Thereafter, CA125/CA19-9 fell as follows: 3776.6/1680.0 (27/5), 2268.4/1145.4 (30/5), 655.1/305.1 (6/6). I performed LSO on May 30, 2008. Her left ovary was enlarged and ruptured. Pathological diagnosis of resected ovary was benign chocolate cyst. She was discharged on June 8, 2008, and followed up at outpatient clinic. On October 8, 2008, CA125 and CA19-9 were 60.6 U/ml, 65.4 U/ml, respectively. She is currently pregnant. Conclusion: This rare case suggests that serum CA125 and CA19-9 measurement may be important in the management of chocolate cyst due to ovarian endometriosis.
Poster presentations / International Journal of Gynecology & Obstetrics 107S2 (2009) S413–S729
P755 Association between endometriosis and haplotype allele of vascular endothelial growth factor K. Jung Gu, P. Kyung Ah, K. Hoon, K. Seung Yup, S. Chang Suk, K. Seok Hyun, C. Young Min, M. Shin Yong. Department of Obstetrics and Gynecology, Seoul National University College of Medicine Objective: To evaluate the association between endometriosis and hapotype allele of vascular endothelial growth factor (VEGF). Materials and Methods: The C(−460)T, C405G and C936T polymorphisms in VEGF gene were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis in 206 women with endometriosis (n = 105) and without endometriosis (n = 101) and their haplotype alleles were analyzed. The serum levels of VEGF were also measured using an enzyme immunoassay. Results: Distributions of C(−460)T, C405G and C936T haplotype alleles were as follow: TCC (36.9%), TGC (22.1%), CGC (20.4%), CGT (10.7%), TCT (6.3%), CCC (1.9%), CCT (1.0%), and TGT (0.7%). Among the haplotype alleles, the frequency of CCC (−460/405/936) haplotype allele was significantly lower in women with endometriosis compared to women without endometriosis (4.0% vs 0.0%, P = 0.01). Serum levels of VEGF in CCC heterozygotes were not different from those in other haplotype genotypes. Conclusion: The CCC haplotype allele of VEGF is one of the genetic factors which may be associated with endometriosis in Korean women. P756 Expression of nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) on the eutopic endometrium of patients with endometriosis S. Seo, B. Lee, S. Cho, H. Kim, Y. Choi, K. Park, D. Cho. Gangnam Severance Hospital Objective: Altered regulation of apoptosis in eutopic endometrium could contribute to survival of endometriotic cell and developed endometriosis. NAG-1, member of transforming growth factor – b (TGF- b) superfamilies, concerns in induction of cell apoptosis. We hypothesized that decreased expression of NAG-1 of eutopic endometrium may be involved in the pathophysiology of endometriosis and investigated the expression of NAG-1 in eutopic endometrium of endometriosis and normal endometrium. Materials and Methods: The relative NAG-1 mRNA expression level of the endometrium was analyzed by real–time RT-PCR in 73 eutopic endometrium (39 from with endometriosis patients and 34 from without endometriosis). Results: NAG-1 mRNA expression of endometrial tissues showed changes through the cycle. That was found decreased as date in proliferative phase (EP, 31.4±23.7, V.S LP, 6.6±6.4, P = 0.000), whereas there was a gradual increase in the secretory phase (ES, 10.3±6.7 V.S LS, 168.2±251.7, P = 0.000). Menstrual and latesecretory phase showed the maximum expression (P = 0.000). When compared NAG-1 mRNA level of each group, during menstrual phase, NAG-1 expressin from endometriosis was significantly lower than the level from women without endometriosis (endometriosis group, 124.7±111.0 V.S control group, 318.0±287.3, P = 0.028). Conclusions: We demonstrated that the presence of NAG-1 in human endometrium and decreased in menstruating eutopic endometrium of endometriosis. Although the role of NAG-1 in human endometriosis is not clear at the present time, it may play a role in the development of endometriois by linked apoptosis.
P757 Investigating novel tumor markers for endometriosis M. Nabeta1 , Y. Abe2 , Y. Kusanagi1 , M. Ito1 , N. Ueda2 . 1 Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, 2 Department of Molecular Pathology, Ehime University Graduate School of Medicine Objectives: Endometriosis, affecting women of reproductive ages, causes pelvic pain and is attributed as the cause of approximately 15% of infertility cases. The diagnosis of endometriosis is traditionally based on laparoscopic visualization; however, this method is worrisome and is not a trivial procedure. Therefore, less invasive methods for the diagnosis of endometriosis have been desired. The purpose of this study was to establish a new diagnostic marker for endometriosis which can be applied more easily on a clinical basis. Material and Methods: Autoantibodies (aAbs) in sera of endometriotic patients and healthy controls were investigated using two-dimensional (2-D) gel electrophoresis, Western blotting and a mesothelial cell line, Meso-1. Proteins at reacted spots were analyzed by MALDI TOF-MS. ELISAs were established by making recombinant proteins and aAbs titers were estimated in sera of endometriotic patients, healthy volunteers and disease control patients. Results: Using 2-D gel electrophoresis and Western blotting, 4 spots were identified as autoantigens specific to endometriosis. These spots were excised from the 2-D gel, and subjected to the MALDI TOF-MS analysis. Proteins A-D were expressed in 2/3–3/3 in Western blotting analysis using patients’ sera. None of these spots were reacted when using healthy volunteers’ sera. After protein identification (Lamin-A/C, Carboxypeptidase O, Aldolase and protein X), recombinant proteins were elaborated. We are currently analyzing these proteins using ELISAs, hoping that they can be applied to the diagnosis of endometriosis. Conclusions: We identified 4 autoantigens for the diagnosis of endometriosis. Further investigation of these proteins is currently underway. P758 A case of ruptured chocolate cyst with extremely high level of serum CA125 and CA19-9 H. Nakachi. Okinawa Syoko Clinic Introduction: A chocolate cyst is one of common benign ovarian tumor due to ovarian endometriosis. Severe abdominal pain complicated with ovarian tumor usually indicates torsion or rupture. The most important clinical implication of CA125 and CA19-9are in the diagnosis and management of ovarian malignancy. I report here a rare case of ruptured benign chocolate cyst complicated severe abdominal pain and fever with extremely high level of serum CA125 and CA19-9. Case report: A 28-year old female 1G1P with ovarian tumor was referred for severe abdominal pain and high fever 38ºC on May 22, 2008. CT reveald cystic tumor on her left adnexa and severe abdominal rebound tenderness was seen. Her clinical signs and symptoms indicate peritonitis. IV antibiotic therapy was started. One day after admission, her abdominal pain and fever disappeared. Her serum CA125 and CA19-9were 6947.1 U/ml, 3647.9 U/ml, respectively. Thereafter, CA125/CA19-9 fell as follows: 3776.6/1680.0 (27/5), 2268.4/1145.4 (30/5), 655.1/305.1 (6/6). I performed LSO on May 30, 2008. Her left ovary was enlarged and ruptured. Pathological diagnosis of resected ovary was benign chocolate cyst. She was discharged on June 8, 2008, and followed up at outpatient clinic. On October 8, 2008, CA125 and CA19-9 were 60.6 U/ml, 65.4 U/ml, respectively. She is currently pregnant. Conclusion: This rare case suggests that serum CA125 and CA19-9 measurement may be important in the management of chocolate cyst due to ovarian endometriosis.