乙醛脱氢酶1和C-kit在复发性子宫内膜息肉组织中的表达及意义
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摘要
目的探讨乙醛脱氢酶1(aldehyde dehydrogenase-1,ALDH1)和C-kit及其配体干细胞因子(stem cell factor,SCF)在复发性子宫内膜息肉(endometrial polyp,EP)组织中的表达及意义。方法选取2014年6月—2017年6月在联勤保障部队第九八〇(白求恩国际和平)医院就诊,根据病史及宫腔镜下取材病理检查确诊为初发EP 30例作为初发组,2次或多次诊断为EP 30例作为复发组。另选取同期在该院就诊,宫腔镜下取材病理检查未发现子宫内膜病变30例作为对照组。采用免疫组织化学PV法检测比较3组ALDH1、B淋巴细胞瘤基因2(Bcl2)及Bax表达,采用Western blot法检测比较3组C-kit及其配体SCF表达。结果 3组ALDH1、Bcl2、Bax、C-kit及SCF均有表达。ALDH1、Bcl2、Bax、Bcl2/Bax及C-kit、SCF 3组总体比较差异均有统计学意义(P <0. 05)。ALDH1、Bcl2、Bcl2/Bax及C-kit、SCF初发组和复发组明显高于对照组,复发组高于初发组,差异有统计学意义(P <0. 05)。Bax初发组和复发组低于对照组,差异有统计学意义(P <0. 05)。结论 ALDH1和C-kit与EP形成及复发有密切关系。ALDH1可能通过影响Bcl2/Bax抑制子宫内膜组织细胞凋亡,促进内膜增生,逐渐形成息肉及导致复发; C-kit及其配体SCF也可能通过影响子宫内膜分化参与该进程。
Objective To investigate expressions and significances of acetaldehyde dehydrogenase-1( ALDH1),C-kit and its ligand stem cell factors( SCF) in recurrent endometrial polyps( EP) tissues. Methods A total of 30 patients,who were diagnosed as having primary EP by case history and pathological results of hysteroscopes in 980 Hospital of PLA Joint Logistics Support Forces during June 2014 and June 2017,were selected as primary group,while other 30 patients with recurrent or multiple EP at the same period were selected as recurrent group,and other 30 patients without endometrium lesions by pathological examination at the same period were selected as control group. Among three groups,expressions of ALDH1,B-cell leukemia-lymphoma-2( Bcl2) and Bax were detected by immunohistochemistry method,and expressions of C-kit protein and its ligand SCF were detected by Western blot method. Results ALDH1,Bcl2,Bax,C-kit and its ligand SCF expressions were all detected among three groups,there were significant differences in ALDH1,Bcl2,Bax,Bcl2/Bax,C-kit protein and its ligand SCF expressions among three groups( P < 0. 05). ALDH1,Bcl2,Bcl2/Bax,C-kit protein and its ligand SCF expressions in primary and recurrent groups were significantly higher than those in control group,and the expressions in recurrent group were significantly higher than those in primary group( P < 0. 05). Bax expressions in primary and recurrent groups were significantly lower than that in control group( P < 0. 05). Conclusion ALDH1 and C-kit are closely related to the pathogenesy and recurrence of endometrial polyps. ALDH1 may inhibit endometrial histiocytes apoptosis by influencing Bcl2/Bax values to promote intimal hyperplasia,and then polyps are gradually formed to induce recurrence. C-kit and its ligand SCF may also participate the processes by influencing endometrial differentiation.
Objective To investigate expressions and significances of acetaldehyde dehydrogenase-1( ALDH1),C-kit and its ligand stem cell factors( SCF) in recurrent endometrial polyps( EP) tissues. Methods A total of 30 patients,who were diagnosed as having primary EP by case history and pathological results of hysteroscopes in 980 Hospital of PLA Joint Logistics Support Forces during June 2014 and June 2017,were selected as primary group,while other 30 patients with recurrent or multiple EP at the same period were selected as recurrent group,and other 30 patients without endometrium lesions by pathological examination at the same period were selected as control group. Among three groups,expressions of ALDH1,B-cell leukemia-lymphoma-2( Bcl2) and Bax were detected by immunohistochemistry method,and expressions of C-kit protein and its ligand SCF were detected by Western blot method. Results ALDH1,Bcl2,Bax,C-kit and its ligand SCF expressions were all detected among three groups,there were significant differences in ALDH1,Bcl2,Bax,Bcl2/Bax,C-kit protein and its ligand SCF expressions among three groups( P < 0. 05). ALDH1,Bcl2,Bcl2/Bax,C-kit protein and its ligand SCF expressions in primary and recurrent groups were significantly higher than those in control group,and the expressions in recurrent group were significantly higher than those in primary group( P < 0. 05). Bax expressions in primary and recurrent groups were significantly lower than that in control group( P < 0. 05). Conclusion ALDH1 and C-kit are closely related to the pathogenesy and recurrence of endometrial polyps. ALDH1 may inhibit endometrial histiocytes apoptosis by influencing Bcl2/Bax values to promote intimal hyperplasia,and then polyps are gradually formed to induce recurrence. C-kit and its ligand SCF may also participate the processes by influencing endometrial differentiation.
引文
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[25] La Point R J,Bourne P A,Wang H L,et al. Coexpression of c-kit and Bcl2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung[J]. Appl Immunohistochem Mol Morphol,2007,15(4):401-406.
[2] Smith P P,O'Connor S,Gupta J,et al. Recurrent postmenopausal bleeding:a prospective cohort study[J]. J Minim Invasive Gyneco1,2014,21(5):799-803.
[3] Dipi R M,Amin M S,Islam M N,et al. Comparison of transabdominal and transvaginal sonography in the evaluation of uterine masswith histopathological correlation[J]. Mymensingh Med J,2013,22(1):69-74.
[4] Paradisi R,Rossi S,Scifo M C,et al. Recurrence of endometrial polyps[J]. Gynecol Obstet Invest,2014,78(1):26-32. Doi:10. 1159/000362646.
[5] Liu Z,Kuokkanen S,Pal L. Steroid hormone receptor profile of premenopausal endometrial polyps[J].Reprod Sci,2010,17(4):377-383. Doi:10. 1177/1933719109356803.
[6] Pereira N,Petrini A C,Lekovich J P,et al. Surgical management of endometrial polyps in infertile women:a comprehensive review[J]. Surg Res Pract,2015,2015:914390.
[7] Maruyama T,Masuda H,Ono M,et al. Human uterine stem/progenitor cells:their possible role in uterine physiology and pathology[J]. Reproduction,2010,140(1):11-22.
[8]高艳霞.乙醛脱氢酶1在子宫内膜息肉组织中的表达及意义[J].临床误诊误治,2016,29(5):102-104.
[9]高艳霞,杨波,董晓红,等. c-kit及其配体干细胞因子在子宫内膜息肉中的表达及意义[J].临床误诊误治,2016,29(8):100-102.
[10] Kabil Kucur S,Temizkan O,Atis A,et al. Role of endometrial power Doppler ultrasound using the international endometrial tumor analysis group classification in predicting intrauterine pathology[J]. Arch Gynecol Obset,2013,288(3):649-654.
[11] Yang J H,Chen C D,Chen S U,et al. Factors influencing the recurrence potential of benign endometrial polyps after hysteroscopic polypectomy[J]. Plos One,2015,10(12):14485.
[12] Schwartz T,Stark A,Pang J,et al. Expression of aldehyde dehydrogenase 1 as a marker of mammary stem cells in benign and malignant breast lesions of Ghanaian women[J]. Cancer,2013,119(3):488-494.
[13] Ginestier C,Wicinski J,Cervera N,et al. Retinoid signaling regulates breast cancer stem cell differentiation[J]. Cell Cycle,2009,8(20):3297-3302.
[14] Jiang F,Qiu Q,Khanna A,et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer[J]. Mol Cancer Res,2009,7(3):330-338.
[15] Toffalini F,Demoulin J B. New insights into the mechanisms of hematopoietic cell transformation by activated receptor tyrosine kinases[J]. Blood,2010,116(14):2429-2437.
[16] Chai Y,Huang Y,Tang H,et al. Role of stem cell growth factor/c-Kit in the pathogenesis of irritable bowel syndrome[J]. Exp Ther Med,2017,13(4):1187-1193.
[17] Vajravelu B N,Hong K U,Al Maqtari T,et al. CKit promotes growth and migration of human cardiac progenitor cells via the PI3K-AKT and MEK-ERK pathways[J]. PLo S One,2015,10(10):e0140798.
[18] Xuebing P,Tinchiu L,Enlan X,et al. Is endometrial polyp formation associated with increased expression of vascular endothelial growth factor and transforming growth factor-beta1?[J]. Eur J Obstet Gynecol Repord Biol,2011,159(1):198-203.
[19] Wang L,Yue Y,Yang X,et al. Platelet derived growth factor alpha(PDGFR alpha)induces the activation of cardiac fibroblasts by activating c-Kit[J].Med Sci Monit,2017,23:3808-3816.
[20] Quash G,Fournet G,Chantepie J,et al. Novel competitive irreversible inhibitors of aldehyde dehydrogenase(ALDH1):restoration ofchemosensitivity of L1210 cells overexpressing ALDH1 and induction of apoptosis in BAF(3)cells overexpressing bcl(2)[J]. Biochem Pharmacol,2002,64(8):1279-1292.
[21] Taylor L J,Jackson T L,Reid J G,et al. The differential expression of oestrogen receptors,progesterone receptors,Bcl2 and Ki67 in endometrial polyps[J]. BJOG,2003,110(9):794-798.
[22] Kang M H,Reynolds C P. Bcl2 inhibitors:targeting mitochondrial apoptotic pathways in cancer therapy[J]. Clin Cancer Res,2009,15(4):1126-1132.
[23] Canuto R A,Muzio G,Salvo R A,et al. The effect of anovel irreversible inhibitor of aldehyde dehydrogenases 1and 3 on tumour cell growth and death[J].Chem Biol Interact,2001,130-132(1-3):209-218.
[24] Yu X,Ruan X,Zhang J,et al. Celastrol Induces Cell Apoptosis and Inhibits the Expression of the AML1-ETO/C-KIT Oncoprotein in t(8; 21)Leukemia[J]. Molecules,2016,21(5).
[25] La Point R J,Bourne P A,Wang H L,et al. Coexpression of c-kit and Bcl2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung[J]. Appl Immunohistochem Mol Morphol,2007,15(4):401-406.