PAX-2、β-catenin及HAND2蛋白在子宫内膜增生症中的表达及其意义
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摘要
目的:探讨PAX-2、β-catenin和HAND2蛋白在良性子宫内膜、不典型增生子宫内膜及高分化子宫内膜样腺癌中的表达水平及其在鉴别诊断中的作用。方法:收集19例单纯性增生子宫内膜、19例复杂性增生子宫内膜、22例复杂性伴不典型性增生子宫内膜和26例高分化子宫内膜样腺癌组织,采用免疫组织化学Envision法检测PAX-2、β-catenin和HAND2蛋白的表达情况。另外收集12例增生期子宫内膜组织作为对照。结果:PAX-2和HAND2蛋白在良性增生性子宫内膜、不典型增生及子宫内膜样腺癌的阳性表达率明显下降(P<0.05);但在不典型增生子宫内膜与高分化子宫内膜样腺癌组织之间的异常表达率差异无统计学意义(P>0.05)。β-catenin在不同类型子宫内膜病变中的异常表达率差异无统计学意义(P>0.05)。结论:PAX-2和HAND2异常表达可能是区别良性子宫内膜增生与肿瘤性子宫内膜增生的有用的标志物。
Objective: To investigate the expression of PAX-2、β-catenin and HAND2 in the development of endometrioid adenocarcinoma,and to discuss the possibility of them as useful biomarkers in clinical diagnosis. Methods: The expressions of PAX-2、β-catenin and HAND2 were detected by immunohistochemical staining in 60 cases of endometrial hyperplasia,26 cases of well-differentiated endometrial cancer,12 cases of normal proliferative endometrium were enrolled as control group. Results: The positive expression of PAX-2 and HAND2 were gradually decreased in normal proliferative endometrium,endometrial atypical hyperplasia and well-differentiated endometrial cancer. The abnormal expression of β-catenin in different endometrium types had no statistical significance. Conclusion: The abnormal expression of PAX-2 and HAND2 are useful markers to identify the benign endometrial hyperplasia and malignancy endometrial hyperplasia.
Objective: To investigate the expression of PAX-2、β-catenin and HAND2 in the development of endometrioid adenocarcinoma,and to discuss the possibility of them as useful biomarkers in clinical diagnosis. Methods: The expressions of PAX-2、β-catenin and HAND2 were detected by immunohistochemical staining in 60 cases of endometrial hyperplasia,26 cases of well-differentiated endometrial cancer,12 cases of normal proliferative endometrium were enrolled as control group. Results: The positive expression of PAX-2 and HAND2 were gradually decreased in normal proliferative endometrium,endometrial atypical hyperplasia and well-differentiated endometrial cancer. The abnormal expression of β-catenin in different endometrium types had no statistical significance. Conclusion: The abnormal expression of PAX-2 and HAND2 are useful markers to identify the benign endometrial hyperplasia and malignancy endometrial hyperplasia.
引文
[1]林仲秋.《FIGO 2015妇癌报告》解读连载二——子宫内膜癌诊治指南解读[J].中国实用妇科与产科杂志,2015(11):986-991.
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[3]JOINER A K,QUICK C M,JEFFUS S K.PAX2 expression in simultaneously diagnosed WHO and EIN classification systems[J].Int J Gynecol Pathol,2015,34(1):40-46.
[4]LIAO X,SIU M K,AU C W,et al.Aberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis throughβ-catenin[J].Mod Pathol,2009,22(6):839-847.
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[6]ECCLES M R,HE S,LEGGE M,et al.PAX genes in development and disease:the role of PAX2 in urogenital tract development[J].Int J Dev Biol,2002,46(4):535-544.
[7]JIA N,WANG J,LI Q,et al.DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer[J].Oncotarget,2016,7(51):84785-84797.
[8]MACDONALD B T,TAMAI K,HE X.Wnt/β-catenin signaling:components,mechanisms,and diseases[J].Dev cell,2009,17(1):9-26.
[9]LIU Y,PATEL L,MILLS G B,et al.Clinical significance of CTNNB1 mutation and Wnt pathway activation in endometrioid endometrial carcinoma[J].J Natl Cancer Inst,2014,106(9):245.
[10]SAEGUSA M,HASHIMURA M,YOSHIDA T,et al.β-Catenin mutations and aberrant nuclear expression during endometrial tumorigenesis[J].Br J Cancer,2001,84(2):209-217.
[11]JONES A,TESCHENDORFF A E,LI Q,et al.Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development[J].PLo S Med,2013,10(11):e1001551.
[12]SHINDOH H,OKADA H,TSUZUKI T,et al.Requirement of heart and neural crest derivatives-expressed transcript 2 during decidualization of human endometrial stromal cells in vitro[J].Fertil Steril,2014,101(6):1781-1790.
[13]FUKUDA T,SHIRANE A,WADA-HIRAIKE O,et al.HAND2-mediated proteolysis negatively regulates the function of estrogen receptorα[J].Mol Med Rep,2015,12(4):5538-5544.
[2]SANDERSON P A,CRITCHLEY H O,WILLIAMS A R,et al.New concepts for an old problem:the diagnosis of endometrial hyperplasia[J].Hum Reprod Update,2017,23(2):232-254.
[3]JOINER A K,QUICK C M,JEFFUS S K.PAX2 expression in simultaneously diagnosed WHO and EIN classification systems[J].Int J Gynecol Pathol,2015,34(1):40-46.
[4]LIAO X,SIU M K,AU C W,et al.Aberrant activation of hedgehog signaling pathway contributes to endometrial carcinogenesis throughβ-catenin[J].Mod Pathol,2009,22(6):839-847.
[5]BUELL-GUTBROD R,CAVALLO A,LEE N,et al.Heart and neural crest derivatives expressed transcript 2(HAND2):a novel biomarker for the identification of atypical hyperplasia and typeⅠendometrial carcinoma[J].Int J Gynecol Pathol,2015,34(1):65-73.
[6]ECCLES M R,HE S,LEGGE M,et al.PAX genes in development and disease:the role of PAX2 in urogenital tract development[J].Int J Dev Biol,2002,46(4):535-544.
[7]JIA N,WANG J,LI Q,et al.DNA methylation promotes paired box 2 expression via myeloid zinc finger 1 in endometrial cancer[J].Oncotarget,2016,7(51):84785-84797.
[8]MACDONALD B T,TAMAI K,HE X.Wnt/β-catenin signaling:components,mechanisms,and diseases[J].Dev cell,2009,17(1):9-26.
[9]LIU Y,PATEL L,MILLS G B,et al.Clinical significance of CTNNB1 mutation and Wnt pathway activation in endometrioid endometrial carcinoma[J].J Natl Cancer Inst,2014,106(9):245.
[10]SAEGUSA M,HASHIMURA M,YOSHIDA T,et al.β-Catenin mutations and aberrant nuclear expression during endometrial tumorigenesis[J].Br J Cancer,2001,84(2):209-217.
[11]JONES A,TESCHENDORFF A E,LI Q,et al.Role of DNA methylation and epigenetic silencing of HAND2 in endometrial cancer development[J].PLo S Med,2013,10(11):e1001551.
[12]SHINDOH H,OKADA H,TSUZUKI T,et al.Requirement of heart and neural crest derivatives-expressed transcript 2 during decidualization of human endometrial stromal cells in vitro[J].Fertil Steril,2014,101(6):1781-1790.
[13]FUKUDA T,SHIRANE A,WADA-HIRAIKE O,et al.HAND2-mediated proteolysis negatively regulates the function of estrogen receptorα[J].Mol Med Rep,2015,12(4):5538-5544.