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泰安市妇幼保健院病理科,山东泰安 271000
[摘 要] 目的 探讨DLC-1和cyclinD1在宫颈鳞状细胞癌中的表达.方法 整群选择2005年1月—2013年12月该院收治的62例宫颈鳞状细胞癌标本、38例宫颈上皮内瘤变标本、26例正常宫颈组织标本,以免疫组化SP法检测3组标本中DLC-1和cyclinD1的表达.结果 DLC-1在宫颈鳞状细胞癌、宫颈上皮内瘤变、正常宫颈组织中的阳性表达率分别为27.4%、76.3%、92.3%,差异有统计学意义(P<,0.05)；高、中、低病理分级DLC-1阳性表达率分别为42.9%、27.9%、16.7%,差异有统计学意义(P<,0.05)；Ⅰ~Ⅱa期DLC-1阳性表达率为41.4%,明显高于Ⅱb~Ⅳ期的15.2%,差异有统计学意义(P<,0.05)；无淋巴结转移DLC-1阳性表达率为34.9%,明显高于有淋巴结转移的10.5%,差异有统计学意义(P<,0.05).cyclinD1在宫颈鳞状细胞癌、宫颈上皮内瘤变、正常宫颈组织中的阳性表达率分别为66.1%、5.3%、0%,差异有统计学意义(P<,0.05)；高、中、低病理分级cyclinD1阳性表达率分别为42.9%、67.4%、75.0%,差异有统计学意义(P<,0.05)；Ⅰ~Ⅱa期cyclinD1阳性表达率为48.3%,明显低于Ⅱb~Ⅳ期的81.8%,差异有统计学意义(P<,0.05)；无淋巴结转移cyclinD1阳性表达率为58.1%,明显低于有淋巴结转移的84.2%,差异有统计学意义(P<,0.05).DLC-1与cyclinD1在宫颈鳞状细胞癌中的表达呈负相关性(r等于-0.519,P<,0.05).结论 DLC-1在宫颈鳞状细胞癌的阳性表达较低,而cyclinD1在宫颈鳞状细胞癌的阳性表达较高,两者均与宫颈鳞状细胞癌发展、侵袭、转移等密切相关.
[关键词] 宫颈鳞状细胞癌；DLC-1；cyclinD1
[中图分类号] R4 [文献标识码] A [文章编号] 1674-074２（２０１5）08（a）－０014-03
Expression and Significance of DLC-1 and CyclinD1 in Cervical Squamous Cell Carcinoma
CHEN Xiao-yan
Pathology department, MCH of Tai&,acute,an city, Tai&,acute,an, ShandongProvince, 271000 China
[Abstract] Objective To investigate the expression of DLC-1 and cyclinD1 in cervical squamous cell carcinoma. Methods 62 cases of cervical squamous cell carcinoma samples, 38 cases of cervical intraepithelial neoplasia samples, 26 cases of normal cervical tissue samples from January 2005 to December 2013 were selected, and the expression of DLC-1 and cyclinD1 were detected by immunohistochemistry SP method. Results The positive expression of DLC-1 in cervical squamous cell carcinoma, cervical intraepithelial neoplasia, and normal cervical tissue, were 27.4%, 76.3%, and 92.3% respectively, the difference was statistically significant (P<,0.05), The positive expression of DLC-1 in high, middle, and low pathological grade were 42.9%、27.9%、16.7% respectively, the difference was statistically significant (P<,0.05), The positive expression of DLC-1 in Ⅰ~Ⅱa was 41.4%, which was significantly higher thanⅡb~Ⅳ15.2%(P<,0.05), The positive expression of DLC-1 in patients without lymph node metastasis was 34.9%, which was significantly higher than patients with lymph node metastasis 10.5%(P<,0.05).The positive expression of cyclinD1 in cervical squamous cell carcinoma, cervical intraepithelial neoplasia, and normal cervical tissue, were 66.1%, 5.3%, 0% respectively, the difference was statistically significant (P<,0.05), The positive expression of cyclinD1 in high, middle, and low pathological grade were 42.9%, 67.4%, 75.0% respectively, the difference was statistically significant (P<,0.05), The positive expression of cyclinD1 in Ⅰ~Ⅱa was 48.3%, which was significantly higher thanⅡb~Ⅳ81.8% (P<,0.05), The positive expression of cyclinD1 in patients without lymph node metastasis was 58.1%, which was significantly higher than patients with lymph node metastasis 84.2% (P<,0.05).The expression of DLC-1 and cyclinD1 in cervical squamous cell carcinoma showed a negative correlation (r等于-0.519, P<,0.05). Conclusion The expression of DLC-1 in squamous cell carcinoma is lower, and expression of cyclinD1 in squamous cell carcinoma is higher, and both of them are closely related to the stage, grade, and lymph node metastasis of squamous cell carcinoma.
宫颈细胞学检查:定期妇检，远离癌变 宫颈癌检测-TCT耗材-液基细胞试剂 中山康乃欣生物医疗科技有限
[Key words] Squamous cell carcinoma,DLC-1, CyclinD1
宫颈癌是妇女临床常见性恶性肿瘤,其发病率仅低于乳腺癌,而其中又以鳞状细胞癌的发病率最高,约70%[1].当前,鳞状细胞癌的发病率逐年增加,且早期临床无明显症状,常在体检中发现.病理学研究显示,宫颈癌的发病过程复杂,涉及癌基因改变和细胞生长的变化[2].DLC-1为抑癌基因,在多数正常组织中的表达较高,在多数肿瘤中的表达较低[3].cyclinD1是原癌基因,高表达可促进细胞增殖[4].当前,DLC-1和cyclinD1在鳞状细胞癌中表达的研究不多见,基于此,通过分析该院2005年1月—2013年12月间收治的62例宫颈鳞状细胞癌标本、38例宫颈上皮内瘤变标本、26例正常宫颈组织中DLC-1和cyclinD1的表达情况,探讨了DLC-1和cyclinD1与鳞状细胞癌发展、侵袭、转移的关系,并对两者的相关性进行了分析.以期为宫颈癌的防治提供数据.现报道如下.
1. 资料与方法
1.1 一般资料
62例宫颈鳞状细胞癌标本、38例宫颈上皮内瘤变标本、26例正常宫颈组织标本均整群选自该院2005年1月—2013年12月病理科,且均经病理证实.62例宫颈鳞状细胞癌中,年龄35~76岁,平均(52.7±12.5)岁；高分化癌7例,中分化癌43例,低分化癌12例；FIGO分期：Ⅰ~Ⅱa期29例,Ⅱb~Ⅳ期33例；无淋巴结转移者43例；有淋巴结转移者19例.患者术前均未进行放疗及化疗的治疗,且标本经病理医师复检.
1.2 方法
标本经10%中性论文范文固定,用石蜡包埋,做4 μm的切片.以SP法进行免疫组化,操作依据试剂盒说明书进行.并用乳腺癌作为阳性对照,PBS组作为阴性对照.
1.3 结果判定
结果判定以双评分法进行[5],观察DLC-1细胞质和cyclinD1的细胞核,当出现棕论文范文颗粒、且染色的强度大于背景着色时,判定为阳性.细胞计分标准：0分,阳性细胞数＜5%；1分,5%~25%；2分,26%~50%；3分,51%~75%；4分,＞75%.显色强度评分：0分,无着色；1分,淡论文范文；2分,棕论文范文；3分,棕褐色.两评分乘积≤1,表示(－)；1~3分,表示弱(+)；＞3,表示(+).
1.4 统计方法
以SPSS 16.0进行统计分析.计数资料用χ2检验.P<,0.05为差异有统计学意义.
2. 结果
2.1 三组标本中DLC-1和cyclinD1的表达
DLC-1在宫颈鳞状细胞癌、宫颈上皮内瘤变、正常宫颈组织中的阳性表达逐渐增大,差异有统计学意义(P<,0.05)；cyclinD1在宫颈鳞状细胞癌、宫颈上皮内瘤变、正常宫颈组织中的阳性表达逐渐减小,差异有统计学意义(P<,0.05).结果见表1.
2.2 DLC-1和cyclinD1与宫颈鳞状细胞癌的关系
DLC-1和cyclinD1在宫颈鳞状细胞癌中的阳性表达与宫颈鳞状细胞癌的分期、分级、淋巴转移密切相关,差异有统计学意义(P<,0.05).结果见表2.
2.3 DLC-1与cyclinD1在宫颈鳞状细胞癌中表达的相关性
DLC-1与cyclinD1在宫颈鳞状细胞癌中表达的呈负相关性(r等于-0.519).结果见表3.
3. 讨论
对于DLC-1在宫颈鳞状细胞癌中的表达,该组研究结果显示：DLC-1在宫颈鳞状细胞癌、宫颈上皮内瘤变、正常宫颈组织中的阳性表达率分别为27.4%、76.3%、92.3%,差异有统计学意义(P<,0.05)；高、中、低病理分级DLC-1阳性表达率分别为42.9%、27.9%、16.7%,差异有统计学意义(P<,0.05)；Ⅰ~Ⅱa期DLC-1阳性表达率为41.4%,明显高于Ⅱb~Ⅳ期的15.2%,差异有统计学意义(P<,0.05)；无淋巴结转移DLC-1阳性表达率为34.9%,明显高于有淋巴结转移的10.5%,差异有统计学意义(P<,0.05).结果提示了：DLC-1在宫颈鳞状细胞癌和宫颈上皮内瘤变中的阳性表达率显著低于正常宫颈组织,并与宫颈鳞状细胞癌的分化、分期、淋巴结转移密切相关.早在1998年,张风林等[5]在肝癌细胞系染色体的研究中首次发现了DLC-1,在基因组染色体中具有低表达.病理研究显示,DLC-1在人体脑、心、肝、肺、乳腺等组织都有表达,并可抑制肺癌、肝癌、前列腺癌等肿瘤细胞的生长,发挥抑癌作用.此外,Seng等[6]的研究发现宫颈癌会对DLC-1的启动子进行论文范文化修饰,造成DLC-1的失活,因此,DLC-1可以作为宫颈癌诊治判断的标记物.宋明芮等[7]的研究结果表明, DLC-1的低表达参与了宫颈鳞状细胞癌的发生、发展、侵袭、及转移,本组结果与其结果一致.
对于cyclinD1在宫颈鳞状细胞癌中的表达,该组发现：cyclinD1在宫颈鳞状细胞癌、宫颈上皮内瘤变、正常宫颈组织中的阳性表达率分别为66.1%、5.3%、0%,差异有统计学意义(P<,0.05)；高、中、低病理分级cyclinD1阳性表达率分别为42.9%、67.4%、75.0%,差异有统计学意义(P<,0.05)；Ⅰ~Ⅱa期cyclinD1阳性表达率为48.3%,明显低于Ⅱb~Ⅳ期的81.8%,差异有统计学意义(P<,0.05)；无淋巴结转移cyclinD1阳性表达率为58.1%,明显低于有淋巴结转移的84.2%,差异有统计学意义(P<,0.05).结果提示了：CyclinD1在宫颈鳞状细胞癌和宫颈上皮内瘤变中的阳性表达率显著高于正常宫颈组织,并与宫颈鳞状细胞癌的分化、分期、淋巴结转移密切相关.CyclinD1是一种参与细胞周期精确调控的蛋白,维持细胞生长发育的平衡.CyclinD1基因的变化可引起细胞周期的异常调控,进而诱发细胞转化、甚至癌变.病理研究显示,CyclinD1可加速G1/S期的转换,促进细胞周期的进程,当CyclinD1的过度表,会造成细胞的持续性增殖,进而形成肿瘤.此外,Shi等[8]的研究发现CyclinD1在宫颈癌组呈现高表达,可作为早期宫颈癌诊治的标志物.王论文范文等[9]的研究显示CyclinD1的高表达促进了细胞周期进程,引起细胞增殖的失控,促进宫颈癌的发生,该组结果与其一致.
在DLC-1和cyclinD1的相关性分析中,发现DLC-1和cyclinD1在宫颈鳞状细胞癌中的表达呈负相关性(r等于-0.519,P<,0.05).结果提示了,DLC-1的低表达和cyclinD1的高表达在宫颈鳞状细胞癌的发生、发展、侵袭中起重要作用.
综上所述,DLC-1在宫颈鳞状细胞癌的阳性表达较低,而cyclinD1在宫颈鳞状细胞癌的阳性表达较高,两者均与宫颈鳞状细胞癌发展、侵袭、转移等密切相关.
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[5] 张风林,丁学华,应奇,等.肝癌缺失基因-1在垂体腺瘤中的表达与腺瘤临床病理特征的关系[J].中华神经医学杂志,2012,11(1):16-19.
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[7] 宋明芮, 成慧, 张晓云, 等.宫颈鳞状细胞癌中DLC-1和cyclinD1的表达及其临床意义[J].诊断病理学杂志,2014,21(10):633-636.
[8] Shi Y, Tao Y, Jiang Y, et al. Nuclear epidermal growth factor receptor interacts with transcriptional intermediary factor 2 to activate cyclin D1 gene expression triggered by the oncoprotein latent membrane protein 1[J]. Carcinogenesis, 2012, 33(8):468-1478.
[9] 王论文范文,刘晓兰,崔涌.PTEN、PDCD5和CyclinD1在宫颈上皮内瘤变及宫颈癌的表达及意义[J].实用医技杂志,2013(2):173-175.
（收稿日期：2015-05-08）
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