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摘要:
目的 探讨ER、Bcl-2蛋白在不同程度宫颈病变中的相关性及意义。 方法 免疫组织化学检测慢性宫颈炎20例、低度宫颈上皮内瘤变30例、高度宫颈上皮内瘤变70例及80例宫颈癌组织中ER和Bcl-2蛋白的表达。 结果 ER在慢性宫颈炎组中阳性率为75%,随着宫颈病变程度的加重,其表达率逐渐降低(χ2=24.266,P < 0.01),与慢性宫颈炎组比较,CINⅡ~Ⅲ组和宫颈鳞癌组差异有统计学意义,CINⅠ组差异无统计学意义(χ2=0.751,P=0.386)。与肿瘤组织类型及病理分级无关;BCL-2在宫颈鳞癌组中阳性率为75.38%,随着宫颈病变程度的加重,其表达率逐渐增高(χ2=27.715,P < 0.01),与慢性宫颈炎组比较,CINⅠ组、CINⅡ~ Ⅲ组及宫颈鳞癌组差异均有统计学意义。与宫颈鳞癌病理分级相关(χ2=4.862,P=0.027),与肿瘤组织类型无关(P=0.500);CIN Ⅱ~Ⅲ组中联合表达阳性率为38.57%(27/70),宫颈鳞癌组中联合表达阳性率为15.38%(10/65),差异具有统计学意义(χ2=9.108,P=0.003)。CINⅡ~Ⅲ组中ER与Bcl-2蛋白表达存在相关(r=0.506,P < 0.01),其余组中无相关关系。 结论 在宫颈病变的进展中,ER和Bcl-2表达呈相反趋势,在CINⅡ~Ⅲ组中有相关性,联合表达阳性可能是宫颈高度上皮内瘤变发生的主要机制之一。 Abstract:Objective This study aimed to investigate the relationship between estrogen receptor (ER) and Bcl-2 in cervical cancer and precancerous lesions. Methods ER and Bcl-2 were evaluated by immunohistochemistry in 20 non-tumor tissues, 30 low-grade cervical intraepithelial neoplasias, 70 high-grade cervical intraepithelial neoplasias, and 80 cervical cancers. Results The positive rate of ER was 75% in non-tumor tissues; this rate decreased with disease severity (χ2=24.266, P < 0.01). The overexpression of ER protein was remarkably lower in cervical intraepithelial neoplasias (CIN) Ⅱ-Ⅲ and carcinomas than in non-tumorous cervices. Differences were not significant between CINⅠ and non-tumorous cervices (χ2=0.751, P=0.386). Furthermore, ER expression was not correlated with histological type and tumor grade. The positive rate of Bcl-2 was 75.38% in squamous cell carcinoma. This rate increased with disease severity (χ2=27.715, P < 0.01). The Bcl-2 protein overexpression was remarkably higher in CINⅠ, CIN Ⅱ-Ⅲ, and carcinomas than in non-tumorous cervices. Bcl-2 expression was also not correlated with histological type (P=0.500); by comparison, Bcl-2 expression was correlated with tumor pathological grade (χ2=4.862, P=0.027). The co-expression of ER and Bcl-2 was 38.57% and 15.38% in CIN Ⅱ-Ⅲand squamous cell carcinoma, respectively; the differences between these two values were significant (χ2=9.108, P=0.003). A correlation between ER and Bcl-2 was observed in CIN Ⅱ-Ⅲ (r=0.506, P < 0.01); no correlation was observed between other groups. Conclusion ER expression was inversely correlated with Bcl-2 in cervical cancer progression. The co-expression of these markers may have an important function in the course of high-grade cervical intraepithelial neoplasia. -
Key words:
- cervical cancer /
- cervical intraepithelial neoplasm /
- estrogen receptor /
- Bcl-2 protein
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图 1 ER和Bcl-2蛋白在不同宫颈病变组织中的表达(ISH×200)
A-F:ER expression in different degrees of cervical lesions. A:Normal cervical tissue;B:CINⅠ;C:CINⅢ;D:Carcinoma in situ with glandular involvement;E:squamous cell carcinoma of uterine cervix;F:Adenocarcinoma of cervix;J:normal cervical tissue;H:Bcl-2 expression in squamous cell carcinoma of uterine cervix
Figure 1. ER and Bcl-2 expressions in different degrees of cervical lesions(ISH×200)
表 1 ER和Bcl-2在不同宫颈病变组织中的表达
Table 1. ER and Bcl-2 expression among different degrees of cervical lesions
表 2 ER和Bcl-2在不同类型宫颈癌组织中的表达
Table 2. ER and Bcl-2 expression among different degrees of cervical cancer lesions
表 3 ER与Bcl-2在不同宫颈病变组织中阳性表达的相关比较
Table 3. Comparison of ER and Bcl-2 expression among different degrees of cervical lesions
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[1] Gariglio P, Gutiérrez J, Cortés E, et al. The role of retinoid deficiency and estrogens as cofactors in cervical cancer[J]. Arch Med Res, 2009, 40(6): 449-465. doi: 10.1016/j.arcmed.2009.08.002 [2] Chung SH, Franceschi S, Lambert PF. Estrogen and ERalpha: culprits in cervical cancer[J]? Trends Endocrinol Metab, 2010, 21(8): 504-511. doi: 10.1016/j.tem.2010.03.005 [3] Thaler S, Schmidt M, Schad A, et al. RASSF1A inhibits estrogen receptor alpha expression and estrogen-independent signalling: implications for breast cancer development[J]. Oncogene, 2012, 31(47): 4912-4922. doi: 10.1038/onc.2011.658 [4] Yu X, Zhang X, Dhakal IB, et al. Induction of cell proliferation and survival genes by estradiol-repressed microRNAs in breast cancer cells[J]. BMC Cancer, 2012, 12(29): 1471-2407. [5] Kahn JA. HPV vaccination for the prevention of cervical intraepithelial neoplasia[J]. N Eng J Med, 2009, 361(3): 271-278. doi: 10.1056/NEJMct0806938 [6] zur Hausen H. Papillomaviruses and cancer: from basic studies to clinical application[J]. Nat Rev Cancer, 2002, 2(5): 342-350. doi: 10.1038/nrc798 [7] Alsbeih G, Al-Harbi N, El-Sebaie M, et al. HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia[J]. Infect Agent Cancer, 2013, 8(1): 15. doi: 10.1186/1750-9378-8-15 [8] Shai A, Pitot HC, Lambert PF. p53 Loss synergizes with estrogen and papillomaviral oncogenes to induce cervical and breast cancers [J]. Cancer Res, 2008, 68(8): 2622-2631. doi: 10.1158/0008-5472.CAN-07-5266 [9] Rinaldi S, Plummer M, Biessy C, et al. Endogenous sex steroids and risk of cervical carcinoma: results from the EPIC study[J]. Cancer Epidemiol Biomarkers Prev, 2011, 20(12): 2532-2540. doi: 10.1158/1055-9965.EPI-11-0753 [10] 王金桃, 高尔生, 丁玲, 等. 内源性雌孕激素及其受体与宫颈癌的关系[J]. 中华肿瘤, 2006, 28(7): 494-497. doi: 10.3760/j.issn:0253-3766.2006.07.004 [11] Zhai Y, Bommer GT, Feng Y, et al. Loss of Estrogen Receptor 1 Enhances Cervical Cancer Invasion[J]. Am J Pathol, 2010, 177(2): 884-895. doi: 10.2353/ajpath.2010.091166 [12] Elson DA, Riley RR, Lacey A, et al. Sensitivity of the cervical transformation zone to estrogen-induced squamous carcinogenesis[J]. Cancer Res, 2000, 60(5): 1267-1275. [13] 赵富玺, 穆雅琴, 郭俊成, 等. Bcl-2 Survivin CD44v6的表达HPV16/ 18感染及其与宫颈癌发生的相关性探讨[J]. 中国肿瘤临床, 2007, 34 (8): 426-429. doi: 10.3969/j.issn.1000-8179.2007.08.002 [14] Dolmetsch RE, Pajvani U, Fife K, et al. Signaling to the nucleus by an L-type calcium channel-calmodulin complex through the MAP kinase pathway[J]. Science, 2001, 294 (5541): 333-339. doi: 10.1126/science.1063395 [15] Dremina ES, Sharov VS, Schöneich C. Heat-shock proteins attenuate SERCA inactivation by the anti-apoptotic protein Bcl-2: possible implications for the ER Ca2+-mediated apoptosis[J]. Biochem J, 2012, 444(1): 127-139. doi: 10.1042/BJ20111114