雌激素硫酸转移酶在肥大乳房乳腺组织中的表达及意义
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摘要
目的测定雌激素硫酸转移酶(estrogen sulfotransferase ,EST)在肥大乳房乳腺组织中的表达状况,以探讨其在乳房肥大发病机制中的作用和意义。
方法采用免疫组织化学EnVision二步法,研究雌激素硫酸转移酶分别在32例肥大乳房标本和15例正常体积乳房标本乳腺组织中的表达状况。此外,还进一步研究了不同类型肥大乳房(19例腺性肥大乳房和13例脂性肥大乳房)标本乳腺组织中雌激素硫酸转移酶的表达状况。
结果雌激素硫酸转移酶的阳性信号表现为棕黄色颗粒主要分布于乳腺导管上皮细胞的细胞浆内,而几乎不分布于脂肪细胞内。32例肥大乳房和15例正常体积乳房标本乳腺组织中的EST阳性表达率分别为34.4%(11/32)和93.3%(14/15),两组间比较差异有统计学意义(P<0.01)。EST在19例腺性肥大乳房和13例脂性肥大乳房标本乳腺组织中的阳性表达率分别为10.5%(2/19)和69.2%(9/13) ,两组间比较差异也有统计学意义(P<0.01)。
结论乳腺组织中雌激素硫酸转移酶的表达减少或者缺失,可能参与肥大乳房的形成。而且与腺性肥大乳房形成的关系较为密切,但可能不是脂性肥大乳房形成的确切病因。雌激素硫酸转移酶在肥大乳房乳腺组织中表达的研究不仅有助于乳房肥大病因的进一步深入与确定,而且可以为肥大乳房的治疗提供新的思路。
Objective To detect the expression of estrogen sulfotransferase(EST) in the mammary gland of the hypertrophic breast ,thus its function and significance in the pathogenesis of breast hypertrophy can be investigated.
Method The mammary gland of samples( from 32 cases hypertrophic breast and 15 cases normal voluminal breast )were examined for EST expression by EnVision two step method immunohistochemistry.With the same method,the expression of EST in the mammary gland was detected in the different types of hypertrophic breast (19 cases gland-associated hypertrophic breast and 13 cases fat-associated hypertrophic breast) tissue specimens.
Results The positive signal of EST was displayed in the way that brown granules were mostly distributed in the cytoplasm of mammary gland duct epithelium,and were hardly distributed in the fat cell. The positive expression rate of EST was 34.4%(11/32) in the mammary gland of the 32 cases hypertrophic breast sample and 93.3%(14/15) in the mammary gland of the 15 cases normal voluminal breast sample,showing a significant difference between the two groups(P<0.01). The positive expression rate of EST was 10.5%(2/19) in the mammary gland of the 19 cases gland-associated hypertrophic breast sample and was 69.2%(9/13) in the mammary gland of the 13 cases fat-associated hypertrophic breast sample, also showing a significant difference between the two groups(P<0.01).
Conclusions Decrease or deletion of EST in the mammary gland may be related to the development of hypertrophic breast.and it may has close connection with gland -associated hypertrophic breast,but not be the definite pathogeny of fat-associated hypertrophic breast.The research on expression of EST in the mammary gland of the hypertrophic breast,was not only contributed to determine the etiology of breast hypertrophy further,but also provided new thinking for the therapy of hypertrophic breast.
方法采用免疫组织化学EnVision二步法,研究雌激素硫酸转移酶分别在32例肥大乳房标本和15例正常体积乳房标本乳腺组织中的表达状况。此外,还进一步研究了不同类型肥大乳房(19例腺性肥大乳房和13例脂性肥大乳房)标本乳腺组织中雌激素硫酸转移酶的表达状况。
结果雌激素硫酸转移酶的阳性信号表现为棕黄色颗粒主要分布于乳腺导管上皮细胞的细胞浆内,而几乎不分布于脂肪细胞内。32例肥大乳房和15例正常体积乳房标本乳腺组织中的EST阳性表达率分别为34.4%(11/32)和93.3%(14/15),两组间比较差异有统计学意义(P<0.01)。EST在19例腺性肥大乳房和13例脂性肥大乳房标本乳腺组织中的阳性表达率分别为10.5%(2/19)和69.2%(9/13) ,两组间比较差异也有统计学意义(P<0.01)。
结论乳腺组织中雌激素硫酸转移酶的表达减少或者缺失,可能参与肥大乳房的形成。而且与腺性肥大乳房形成的关系较为密切,但可能不是脂性肥大乳房形成的确切病因。雌激素硫酸转移酶在肥大乳房乳腺组织中表达的研究不仅有助于乳房肥大病因的进一步深入与确定,而且可以为肥大乳房的治疗提供新的思路。
Objective To detect the expression of estrogen sulfotransferase(EST) in the mammary gland of the hypertrophic breast ,thus its function and significance in the pathogenesis of breast hypertrophy can be investigated.
Method The mammary gland of samples( from 32 cases hypertrophic breast and 15 cases normal voluminal breast )were examined for EST expression by EnVision two step method immunohistochemistry.With the same method,the expression of EST in the mammary gland was detected in the different types of hypertrophic breast (19 cases gland-associated hypertrophic breast and 13 cases fat-associated hypertrophic breast) tissue specimens.
Results The positive signal of EST was displayed in the way that brown granules were mostly distributed in the cytoplasm of mammary gland duct epithelium,and were hardly distributed in the fat cell. The positive expression rate of EST was 34.4%(11/32) in the mammary gland of the 32 cases hypertrophic breast sample and 93.3%(14/15) in the mammary gland of the 15 cases normal voluminal breast sample,showing a significant difference between the two groups(P<0.01). The positive expression rate of EST was 10.5%(2/19) in the mammary gland of the 19 cases gland-associated hypertrophic breast sample and was 69.2%(9/13) in the mammary gland of the 13 cases fat-associated hypertrophic breast sample, also showing a significant difference between the two groups(P<0.01).
Conclusions Decrease or deletion of EST in the mammary gland may be related to the development of hypertrophic breast.and it may has close connection with gland -associated hypertrophic breast,but not be the definite pathogeny of fat-associated hypertrophic breast.The research on expression of EST in the mammary gland of the hypertrophic breast,was not only contributed to determine the etiology of breast hypertrophy further,but also provided new thinking for the therapy of hypertrophic breast.
引文
[1]秦映芬,沈寒蕾,黄松,等.巨乳症的临床与病理学观察.临床与实验病理学杂志,2004,20(3):292-294.
[2] Chetrite GS, Cortes-Prieto J, Philippe JC, et al. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol, 2000,72(1-2):24-26.
[3]张勇,孙家明.芳香化酶P450在肥大乳房乳腺组织中的表达.中华整形外科杂志,2009,25(2):136-139.
[4] Coughtrie MWH, Sharp S, Maxwell K, et al. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases.Chem Biol Interact ,1998, 109(1-3):3–27.
[5]王敏,王静云,王欣彦,等.硫酸基转移酶基因在正常子宫内膜组织中的表达及意义.中华妇产科杂志,2007,42(10):708-710.
[6] Her CH ,Aksoy IA , Kimura S,et al.Human estrogen sulfotransferase gene (STE):cloning,structure,and chromosomal localization .Genomics,1995,29(1):16-23.
[7] Aksoy IA,Wood TC ,Weinshilboum R, et al.Human liver estrogen sulfotransferase: identification by cDNA cloning and expression .Biochem Biophys Res Commun, 1994 , 200(3):1621 -1629 .
[8] Falany JL ,Azziz R ,Falany CN.Identification and characterization of cytosolic sulfotransferases in normal human endometrium.Chem Biol Interact ,1998, 109(1-3):329-339.
[9] Duanmu Z, Weckle A, Koukouritaki SB, et al. Developmental expression of aryl,estrogen, and hydroxysteroid sulfotransferases in pre- and postnatal human liver. J Pharmacol Exp Ther,2006,316(3):1310–1317.
[10] Wild MJ,Rudland PS, Back DJ.Metabolism of the oral contraceptive steriods ethynylestradiol and norgestimate by normal (Huma 7) and malignant (MCF -7 and ZR-75-1) human breast cells in culture.J Steriod Biochem Mol Biol ,1991,39(4A):535-543.
[11]邓文慧,吴宜勇,杨丽,等.雌激素硫酸转移酶和B1N1蛋白在乳腺癌组织中的基因表达及其意义.癌症,2004,23(11):1302-1305.
[12] Nakata T, Takashima S, Shiotsu Y, et al. Role of steroid sulfatase in local formation of estrogen in post-menopausal breast cancer patients.J Steroid Biochem Mol Biol, 2003,86(3-5):455–460.
[13] Nowell S, Ratnasinghe DL, Ambrosone CB, et al.Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.Cancer Epidemiol Biomarkers Prev,2004,13(2):270–276.
[14] Utsunomiya H,Ito K,Suzuki T,et al.Steroid sulphatase and estrogen sulphotransferase in human endometrial carcinoma.Clin Cancer Res, 2004,10(17):5850–5856.
[15] Suzuki T, Miki Y, Nakata T, et al. Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma. J Steroid Biochem Mol Biol, 2003,86 (3-5):449–454.
[16] Suzuki T, Nakata T, Miki Y, et al. Estrogen sulfotransferase steroid sulfatase in human breast carcinoma, Cancer Res. 2003,63(11):2762–2770.
[17] Reich O, Singer C, Hudelist G, et al. Estrogen sulfotransferase expression in endometrial stromal sarcomas: An immunohistochemical study. Pathol Res Pract , 2007, 203 (2):85–87.
[18] Sigurdson LJ, Kirkland SA. Breast volume determination in breast hypertrophy: an accurate method using two anthropomorphic measurements. Plast Reconstr Surg,2006,118(2): 313-320.
[19]乔群,凌诒淳,周刚,等.中国125名青年女性乳房体积测量.中华整形烧伤外科杂志,1991,7(1):1—3.
[20] Dancey A, Khan M, Dawson J, et al. Gigantomastia-a classification and review of the literature . J Plast Reconstr Aesthet Surg, 2008,61(5):493.
[21]孙家明,乔群,戚可名.肥大乳房和小乳房乳腺组织中雌激素受体的表达.中华整形外科杂志,2004 ,20 (6):409—411.
[22] Pasqualini JR, Chetrite GS.Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer. J Steriod Biochem Mol Biol ,2005 ,93(2-5) :231.
[1] Dancey A, Khan M, Dawson J, et al. Gigantomastia-a classification and review of the literature . J Plast Reconstr Aesthet Surg,2008,61(5):493.
[2] Arscott GD, Craig HR, Gabay L. Failure of bromocriptine therapy to control juvenile mammary hypertrophy. Br J Plast Surg,2001,54(8):720-721.
[3] Lewison EF, Jones GS, Trimble FH, et al. Gigantomastia complicating pregnancy. Surg Gynecol Obstet ,1960,110: 215-23.
[4] Baker SB, Burkey BA, Thornton P, et al. Juvenile gigantomastia:presentation of four cases and review of the literature. Ann Plast Surg ,2001,46(5):517-525.
[5] Gliosci A, Presutti F. Virginal gigantomastia: validity of combined surgical and hormonal treatments. Aesthetic Plast Surg,1993,17(1):61-65.
[6] Kulkarni D, Beechey-Newman N, Hamed H, et al. Gigantomastia: A problem of local recurrence. Breast, 2006 ,15(1):100-102.
[7]Aritaki S, Miyazawa H, Ogihara M, et al.An endocrinological study of persistent pubertal macromastia. Tohoku J Exp Med, 1992 ,167(3):189-196.
[8]秦映芬,沈寒蕾,黄松,等.巨乳症的临床与病理学观察.临床与实验病理学杂志,2004,20(3):292-294.
[9] Kupfer D, Dingman D, Broadbent R. Juvenile breast hypertrophy: report of a familial pattern and review of the literature. Plast Reconstr Surg ,1992,90(2):303–309.
[10]张勇,孙家明.芳香化酶P450在肥大乳房乳腺组织中的表达.中华整形外科杂志,2009,25(2):136-139.
[11] Chen S, Itoh L,Wu K, et al. Transcrip tional regulation of aromotase expression in human breast tissue. J Steriod BioMol Bio, 2003, 83(1-5): 93-99.
[12]Lu D, Kiriyama Y, Lee KY, et al. Transcription regulation of the estrogen-inducible pS2 breaset cancer marker gene by ERR family of orphan nuclear receptors. Cancer Res, 2001,61(18): 6755-6761.
[13]王介聪,孙家明.雌激素受体相关受体a在乳房肥大中的表达.中国美容整形外科杂志,2008,19(4):307-309.
[14] Noczynska A, Wasikowa R, Myczkowski T. Hypersensitivity of estrogenreceptors as a cause of gigantomasty in two girls. Pol Merkuriusz Lek ,2001,11(66):507–509.
[15] Govrin-Yehudain J, Kogan L, Cohen H, et al. Familial juvenilehypertrophy of the breast. J Adolesc Health ,2004,35(2)151-155.
[16] Pulzl P, Schoeller T, Tzankov A, et al. Unilateral breast enlargement5 years after reduction mammaplasty. Aesth Plast Surg,2005,29(5):404-406.
[17] Koves I, Zacharin M. virginal breast hypertrophy ofan 11-year-old girl. J Paediatr Child Health, 2007,43(4):315-317.
[18] Wechselberger G, Pülzl P, Pichler M ,et al.Juvenile gigantomastia treated by reduction mammoplasty. Am J Surg,2004 ,188(3):333-334.
[19]孙家明,乔群,戚可名.肥大乳房和小乳房乳腺组织中雌激素受体的表达.中华整形外科杂志,2004 ,20 (6):409—411.
[20]张芾男,滕利,杨锴,等.青春期乳房肥大症乳腺组织中雌激素受体的表达.中国美容医学,2007,16 (2):156-158.
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[2] Chetrite GS, Cortes-Prieto J, Philippe JC, et al. Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues. J Steroid Biochem Mol Biol, 2000,72(1-2):24-26.
[3]张勇,孙家明.芳香化酶P450在肥大乳房乳腺组织中的表达.中华整形外科杂志,2009,25(2):136-139.
[4] Coughtrie MWH, Sharp S, Maxwell K, et al. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases.Chem Biol Interact ,1998, 109(1-3):3–27.
[5]王敏,王静云,王欣彦,等.硫酸基转移酶基因在正常子宫内膜组织中的表达及意义.中华妇产科杂志,2007,42(10):708-710.
[6] Her CH ,Aksoy IA , Kimura S,et al.Human estrogen sulfotransferase gene (STE):cloning,structure,and chromosomal localization .Genomics,1995,29(1):16-23.
[7] Aksoy IA,Wood TC ,Weinshilboum R, et al.Human liver estrogen sulfotransferase: identification by cDNA cloning and expression .Biochem Biophys Res Commun, 1994 , 200(3):1621 -1629 .
[8] Falany JL ,Azziz R ,Falany CN.Identification and characterization of cytosolic sulfotransferases in normal human endometrium.Chem Biol Interact ,1998, 109(1-3):329-339.
[9] Duanmu Z, Weckle A, Koukouritaki SB, et al. Developmental expression of aryl,estrogen, and hydroxysteroid sulfotransferases in pre- and postnatal human liver. J Pharmacol Exp Ther,2006,316(3):1310–1317.
[10] Wild MJ,Rudland PS, Back DJ.Metabolism of the oral contraceptive steriods ethynylestradiol and norgestimate by normal (Huma 7) and malignant (MCF -7 and ZR-75-1) human breast cells in culture.J Steriod Biochem Mol Biol ,1991,39(4A):535-543.
[11]邓文慧,吴宜勇,杨丽,等.雌激素硫酸转移酶和B1N1蛋白在乳腺癌组织中的基因表达及其意义.癌症,2004,23(11):1302-1305.
[12] Nakata T, Takashima S, Shiotsu Y, et al. Role of steroid sulfatase in local formation of estrogen in post-menopausal breast cancer patients.J Steroid Biochem Mol Biol, 2003,86(3-5):455–460.
[13] Nowell S, Ratnasinghe DL, Ambrosone CB, et al.Association of SULT1A1 phenotype and genotype with prostate cancer risk in African-Americans and Caucasians.Cancer Epidemiol Biomarkers Prev,2004,13(2):270–276.
[14] Utsunomiya H,Ito K,Suzuki T,et al.Steroid sulphatase and estrogen sulphotransferase in human endometrial carcinoma.Clin Cancer Res, 2004,10(17):5850–5856.
[15] Suzuki T, Miki Y, Nakata T, et al. Steroid sulfatase and estrogen sulfotransferase in normal human tissue and breast carcinoma. J Steroid Biochem Mol Biol, 2003,86 (3-5):449–454.
[16] Suzuki T, Nakata T, Miki Y, et al. Estrogen sulfotransferase steroid sulfatase in human breast carcinoma, Cancer Res. 2003,63(11):2762–2770.
[17] Reich O, Singer C, Hudelist G, et al. Estrogen sulfotransferase expression in endometrial stromal sarcomas: An immunohistochemical study. Pathol Res Pract , 2007, 203 (2):85–87.
[18] Sigurdson LJ, Kirkland SA. Breast volume determination in breast hypertrophy: an accurate method using two anthropomorphic measurements. Plast Reconstr Surg,2006,118(2): 313-320.
[19]乔群,凌诒淳,周刚,等.中国125名青年女性乳房体积测量.中华整形烧伤外科杂志,1991,7(1):1—3.
[20] Dancey A, Khan M, Dawson J, et al. Gigantomastia-a classification and review of the literature . J Plast Reconstr Aesthet Surg, 2008,61(5):493.
[21]孙家明,乔群,戚可名.肥大乳房和小乳房乳腺组织中雌激素受体的表达.中华整形外科杂志,2004 ,20 (6):409—411.
[22] Pasqualini JR, Chetrite GS.Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer. J Steriod Biochem Mol Biol ,2005 ,93(2-5) :231.
[1] Dancey A, Khan M, Dawson J, et al. Gigantomastia-a classification and review of the literature . J Plast Reconstr Aesthet Surg,2008,61(5):493.
[2] Arscott GD, Craig HR, Gabay L. Failure of bromocriptine therapy to control juvenile mammary hypertrophy. Br J Plast Surg,2001,54(8):720-721.
[3] Lewison EF, Jones GS, Trimble FH, et al. Gigantomastia complicating pregnancy. Surg Gynecol Obstet ,1960,110: 215-23.
[4] Baker SB, Burkey BA, Thornton P, et al. Juvenile gigantomastia:presentation of four cases and review of the literature. Ann Plast Surg ,2001,46(5):517-525.
[5] Gliosci A, Presutti F. Virginal gigantomastia: validity of combined surgical and hormonal treatments. Aesthetic Plast Surg,1993,17(1):61-65.
[6] Kulkarni D, Beechey-Newman N, Hamed H, et al. Gigantomastia: A problem of local recurrence. Breast, 2006 ,15(1):100-102.
[7]Aritaki S, Miyazawa H, Ogihara M, et al.An endocrinological study of persistent pubertal macromastia. Tohoku J Exp Med, 1992 ,167(3):189-196.
[8]秦映芬,沈寒蕾,黄松,等.巨乳症的临床与病理学观察.临床与实验病理学杂志,2004,20(3):292-294.
[9] Kupfer D, Dingman D, Broadbent R. Juvenile breast hypertrophy: report of a familial pattern and review of the literature. Plast Reconstr Surg ,1992,90(2):303–309.
[10]张勇,孙家明.芳香化酶P450在肥大乳房乳腺组织中的表达.中华整形外科杂志,2009,25(2):136-139.
[11] Chen S, Itoh L,Wu K, et al. Transcrip tional regulation of aromotase expression in human breast tissue. J Steriod BioMol Bio, 2003, 83(1-5): 93-99.
[12]Lu D, Kiriyama Y, Lee KY, et al. Transcription regulation of the estrogen-inducible pS2 breaset cancer marker gene by ERR family of orphan nuclear receptors. Cancer Res, 2001,61(18): 6755-6761.
[13]王介聪,孙家明.雌激素受体相关受体a在乳房肥大中的表达.中国美容整形外科杂志,2008,19(4):307-309.
[14] Noczynska A, Wasikowa R, Myczkowski T. Hypersensitivity of estrogenreceptors as a cause of gigantomasty in two girls. Pol Merkuriusz Lek ,2001,11(66):507–509.
[15] Govrin-Yehudain J, Kogan L, Cohen H, et al. Familial juvenilehypertrophy of the breast. J Adolesc Health ,2004,35(2)151-155.
[16] Pulzl P, Schoeller T, Tzankov A, et al. Unilateral breast enlargement5 years after reduction mammaplasty. Aesth Plast Surg,2005,29(5):404-406.
[17] Koves I, Zacharin M. virginal breast hypertrophy ofan 11-year-old girl. J Paediatr Child Health, 2007,43(4):315-317.
[18] Wechselberger G, Pülzl P, Pichler M ,et al.Juvenile gigantomastia treated by reduction mammoplasty. Am J Surg,2004 ,188(3):333-334.
[19]孙家明,乔群,戚可名.肥大乳房和小乳房乳腺组织中雌激素受体的表达.中华整形外科杂志,2004 ,20 (6):409—411.
[20]张芾男,滕利,杨锴,等.青春期乳房肥大症乳腺组织中雌激素受体的表达.中国美容医学,2007,16 (2):156-158.
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