자궁내막증 진단을 위한 생표지자의 유용성 = Useful Biomarkers for the Diagnosis of Endometriosis

국문 초록 (Abstract)

진단적 복강경을 하지 않으면 자궁내막증의 진단이 불가능하다는 점은 의사들이 해결해야 할 과제 중 하나이다. 아직까지는 자궁내막증을 진단할 수 있는 획기적인 표지자가 없기 때문에 CA-125 같은 종양 표지자의 혈중 농도를 측정하였으나 진단 도구로 이용하기에는 한계가 있다. 이러한 이유로 초기 자궁내막증을 진단할 수 있는 방법을 연구하기 위한 여러 시도들이 있었는데 특히 자궁내막증 1, 2기 환자에서 병의 초기 상태에 복강경적 치료를 하였을 경우 자연 임신 성공률이 2배 가까이 높은 것으로 보고되었기 때문에 불임 여성에 있어 자궁내막증의 진단 시기는 임상적으로도 그 중요성이 매우 크다고 할 수 있겠다. CA-125는 자궁내막증 환자의 추적관찰에 있어 특이도가 높은 편이며 효용성이 있는데 특히 수술적 치료 후 장기적으로 병의 활성 혹은 재발을 평가하는데 있어 유용하다. 무작위적인 임상 연구 결과 자궁내막증과 관련된 불임이나 통증은 수술적 치료시 분명한 이득이 있는 것으로 보고된 바84 자궁내막증은 적절한 진단과 치료가 중요한 질환이라는 점을 다시 한번 상기해야 한다. 또한 병의 진행에 따른 여러 면역학적인 변화들이 확인되면서 자궁내막증의 진단에 있어 면역학적 표지자의 중요성이 부각되고 있다. 그 중에서도 복막액이나 혈청 내 사이토카인은 진단 도구로서 그 가능성에 주목을 받고 있으며 이에 대한 대규모 연구가 추후 필요할 것으로 사료된다. 최근의 면역학적 발견과 DNA 기술 발전은 자궁내막증의 진단에 있어 핵심적인 screening 도구의 발견에 일조할 것이며 이러한 기술적 발전을 근간으로 하여 머지 않아 획기적인 표지자가 개발될 것으로 기대한다.

참고문헌 (Reference)

1 Bishara S, "http://dx.doi.org/10.1016/j.ejogrb.2007.05.012" Eur J Obstet Gynecol Reprod Biol

2 Lebovic DI, "Vascular endothelial growth factor in reproductive biology" (11) : 255-260, 1999

3 Donnez J, "Vascular endothelial growth factor (VEGF) in endometriosis" (13) : 1686-1690, 1998

4 Evers JL, "Van der Linden PJ. Markers for endometriosis" (7) : 715-739, 1993

5 Harada T, "Usefulness of CA19-9 versus CA 125 for the diagnosis of endometriosis" (78) : 733-739, 2002

6 Somigliana E, "Use of serum-soluble intercellular adhesion molecule-1 as a new marker of endometriosis" (77) : 1028-1031, 2002

7 Vidal F, "Upregulation of vascular endothelial growth factor receptor Flt-1 after endothelial denudation: role of transcription factor Egr-1" (95) : 3387-3395, 2000

8 Matalliotakis I, "Unexpected increase of the CA 19-9 tumour marker in patients with endometriosis" (19) : 498-500, 1998

9 Hunt JS, "Tumor necrosis factor-alpha messenger ribonucleic acid and protein in human endometrium" (47) : 141-147, 1992

10 Eisermann J, "Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery" (50) : 573-579, 1988

11 Takayama K, "Treatment of severe postmenopausal endometriosis with an aromatase inhibitor" (69) : 709-713, 1998

12 Nothnick WB, "Treating endometriosis as an autoimmune disease" (76) : 223-231, 2001

13 Pittaway DE, "The use of CA-125in the diagnosis and management of endometriosis" (46) : 790-795, 1986

14 Rodrigues LR, "The role of osteopontin in tumor progression and metastasis in breast cancer" (16) : 1087-1097, 2007

15 Laird SM, "The production of placental protein 14 and interleukin 6 by human endometrial cells in culture" (8) : 793-798, 1993

16 Mol BW, "The performance of CA-125 measure- ment in the detection of endometriosis: a metaanalysis" (70) : 1101-1108, 1998

17 Wu MH, "The expression of soluble intercellular adhesion molecule-1 in endometriosis" (70) : 1139-1142, 1998

18 Liaw L, "The adhesive and migratory effects of osteopontin are mediated via distinct cell surface integrins. Role of alpha v beta 3 in smooth muscle cell migration to osteopontin in vitro" (95) : 713-724, 1995

19 Aref S, "Soluble VEGF / sFLt1 ratio is an independent predictor of AML patient outcome" (10) : 131-134, 2005

20 Matalliotakis IM, "Soluble ICAM-1 levels in the serum of endometriotic patients appear to be independent of medical treatment" (51) : 9-19, 2001

21 Kumar H, "Soluble FLT-1 is detectable in the sera of colorectal and breast cancer patients" (22) : 1877-1880, 2002

22 De Placido G, "Serum concentrations of soluble human leukocyte class I antigens and of the soluble intercellular adhesion molecule-1 in endometriosis: relationship with stage and non-pigmented peritoneal lesions" (13) : 3206-3210, 1998

23 Moretuzzo RW, "Serum and peritoneal lavage fluid CA-125 levels in endometriosis" (50) : 430-433, 1988

24 Barbati A, "Serum and peritoneal fluid CA-125 levels in patients with endometriosis" (61) : 438-442, 1994

25 Pittaway DE, "Serum CA-125 antigen levels increase during menses" (156) : 75-76, 1987

26 Fedele L, "Serum CA 125 measurements in the diagnosis of endometriosis recurrence" (72) : 19-22, 1988

27 "Revised American Fertility Society classification of endo- metriosis" (43) : 351-352, 1985

28 Dvorak HN, "Regulation of extravascular coagulation bmicrovascular permeability" (227) : 1059-1061, 1985

29 Zahorec R, "Ratio of neutrophil to lymphocyte counts-rapid and simple parameter of systemic inflammation and stress in critically ill" (102) : 5-14, 2001

30 Bedaiwy MA, "Prediction of endometriosis with serum and peritoneal fluid markers: a prospective controlled trial" (17) : 426-431, 2002

31 Mai KT, "Perkins DG, Parks W. Pathogenetic role of the stromal cells in endometriosis and adenomyosis" (30) : 430-442, 1997

32 Braun DP, "Peritoneal fluid-mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis" (78) : 727-732, 2002

33 Syrop CH, "Peritoneal fluid environment and infertility" (48) : 1-9, 1987

34 Shifren JL, "Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis" (81) : 3112-3118, 1996

35 Apparao KB, "Osteopontin and its receptor alpha v beta(3) integrin are coexpressed in the human endo- metrium during the menstrual cycle but regulated differentially" (86) : 4991-5000, 2001

36 Reinholt FP, "Osteopontin - a possible anchor of osteoclasts to bone" (87) : 4473-4475, 1990

37 Cho SH, "Neutrophil-to-lymphocyte ratio as an adjunct to CA 125 for the diagnosis of endometriosis" (90) : 2073-2079, 2008

38 Walsh SR, "Neutrophil-lymphocyte ratio as a prognostic factor in colorectal cancer" (91) : 181-184, 2005

39 Tsudo T, "Nagano Y, Ito M, et al. Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues" (73) : 205-211, 2000

40 Marcoux S, "Laparoscopic surgery in infertile women with minimal or mild endometriosis. Canadian Collaborative Group on Endometriosis" (337) : 217-222, 1997

41 Ortiz BD, "Kinetics of transcription factors regulating the RANTES chemokine gene reveal a developmental switch in nuclear events during T-lymphocyte maturation" (16) : 202-210, 1996

42 Van Langendonckt A, "Iron overload in the peritoneal cavity of women with pelvic endometriosis" (78) : 712-718, 2002

43 Tseng JF, "Interleukin-6 secretion in vitro is upregulated in ectopic and eutopic endometrial stromal cells from women with endometriosis" (81) : 1118-1122, 1996

44 Harada T, "Increased interleukin-6 levels in peritoneal fluid of infertile patients with active endometriosis" (176) : 593-597, 1997

45 Hornung D, "Immunolocalization and regulation of the chemokine RANTES in human endometrial and endometriosis tissues and cells" (82) : 1621-1628, 1997

46 Odagiri K, "Immunohistochemical study of osteopontin and L-selectin in a rat endometriosis model and in human endometriosis" (88) : 1207-1211, 2007

47 Nisolle M, "Immunohistochemical analysis of proliferative activity and steroid receptor expression in peritoneal and ovarian endometriosis" (68) : 912-919, 1997

48 Vaisse C, "Human placental protein 14 gene: sequence and characterization of a short duplication" (9) : 401-413, 1990

49 Bouquet de Joliniere J, "Human endometriosis-derived permanent cell line (FbEM-1): establishment and char- acterization" (3) : 117-123, 1997

50 Kao LC, "Global gene profiling in human endometrium during the window of implantation" (143) : 2119-2138, 2002

51 Stefansson H, "Genetic factors contribute to the risk of developing endometriosis" (17) : 555-559, 2002

52 Ilhan N, "Functional significance of vascular endothelial growth factor and its receptor (receptor-1) in various lung cancer types" (37) : 840-845, 2004

53 Meden H, "Fattahi-Meibodi A. CA 125 in benign gynecological conditions" (13) : 231-237, 1998

54 Philippeaux MM, "Expression of tumor necrosis factor-alpha and its mRNA in the endometrial mucosa during the menstrual cycle" (143) : 480-486, 1993

55 Kitawaki J, "Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium" (57) : 514-519, 1997

56 Brown LF, "Expression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces" (3) : 1169-1180, 1992

57 Cho SH, "Evaluation of serum and urinary angiogenic factors in patients with endometriosis" (58) : 497-504, 2007

58 Bulun SE, "Estrogen production in endometriosis and use of aromatase inhibitors to treat endometriosis" (6) : 293-301, 1999

59 Hsu CC, "Enhanced interleukin¬4 expression in patients with endometriosis" (67) : 1059-1064, 1997

60 Vigano P, "Endometrial release of soluble intercellular adhesion molecule 1 and endometriosis: relationship to the extent of the disease" (95) : 115-118, 2000

61 Cho SH, "Endometrial osteoponin mRNA expression and Plasma osteopontin levels are increased in patients with endometriosis" (61) : 286-293, 2009

62 Taylor RN, "Emerging role of genomics in endometriosis research" (78) : 694-698, 2002

63 Simon C, "Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist" (134) : 521-528, 1994

64 Yan SF, "Egr-1: is it always immediate and early?" (105) : 553-554, 2000

65 Yan SF, "Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress" (6) : 1355-1361, 2000

66 Jiang J, "Effect of mifepristone on estrogen and progesterone receptors in human endometrial and endometriotic cells in vitro" (77) : 995-1000, 2002

67 Daniel Y, "Do soluble cell adhesion molecules play a role in endometriosis?" (43) : 160-166, 2000

68 Eyster KM, "DNA microarray analysis of gene expression markers of endo- metriosis" (77) : 38-42, 2002

69 Koyama N, "Cytokines in the peritoneal fluid of patients with endometriosis" (43) : 45-50, 1993

70 Syrop CH, "Cyclic changes of peritoneal fluid parameters in normal and infertile patients" (69) : 416-418, 1987

71 Taketani Y, "Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis" (167) : 265-270, 1992

72 Koprowski H, "Colorectal carcinoma antigens detected by hybridoma antibodies" (5) : 957-971, 1979

73 Pittaway DE, "Clinical evaluation of CA-125 concentrations as a prognostic factor for pregnancy in infertile women with surgically treated endometriosis" (64) : 321-324, 1995

74 Matthews CJ, "Character- ization of human purified epithelial and stromal cells from endometrium and endometriosis in tissue culture" (57) : 990-997, 1992

75 Zeitoun KM, "Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target" (72) : 961-969, 1999

76 Bulun SE, "Aromatase as a therapeutic target in endometriosis" (11) : 22-27, 2000

77 Dheenadayalu K, "Aromatase P450 messenger RNA expressionin eutopic endometrium is not a specific marker for pelvic endometriosis" (78) : 825-829, 2002

78 Taylor RN, "Angiogenic factors in endometriosis" (955) : 90-100, 2002

79 Taylor RN, "Angiogenesis and macrophage activation in endometriosis" (828) : 194-207, 1997

80 Rier SE, "Altered interleukin-6 production by peritoneal leukocytes from patients with endometriosis" (61) : 294-299, 1994

81 D'Angelo G, "Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin" (92) : 6374-6378, 1995

82 Halme J, "Accentuated cyclic activation of peritoneal macrophages in patients with endometriosis" (148) : 85-90, 1984

83 De Angulo G, "Absolute lymphocyte count is a novel prognostic indicator in ALL and AML: implications for risk stratification and future studies" (112) : 407-415, 2008

84 Hu DD, "A biochemical characterization of the binding of osteopontin to integrins alpha v beta 1 and alpha v beta 5" (270) : 26232-26238, 1995