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乳腺癌患者中人乳头瘤病毒16和Epstein-Barr病毒感染的初步研究

Preliminary study on human papilloma virus 16 and Epstein-Barr virus infections in breast cancer patients

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【作者】 贺晨阳王廷吕勇刚张聚良李永平赵戈马福成刘家云陈江浩王岭

【Author】 He Chenyang;Wang Ting;Lyu Yonggang;Zhang Juliang;Li Yongping;Zhao Ge;Ma Fucheng;Liu Jiayun;Chen Jianghao;Wang Ling;Department of Vascular and Endocrine Surgery,Xijing Hospital,the Fourth Military Medical University;

【机构】 第四军医大学附属西京医院血管内分泌外科第四军医大学附属西京医院病理科第四军医大学附属西京医院检验科

【摘要】 目的探讨人乳头瘤病毒16(HPV16)和Epstein-Barr病毒(EBV)在不同病理类型乳腺癌及乳腺良性病变中的表达。方法采用PCR方法对2013年6月至2014年6月本院收治的90例不同病理类型的乳腺癌(40例浸润性导管癌、30例浸润性小叶癌,20例原位癌)、20例乳腺纤维瘤以及10例乳腺正常组织标本HPV16的E6基因位点和EBV的内部重复序列Bam HIW区域进行扩增,并采用免疫组织化学方法对上述标本进行HPV16和EBV潜在膜蛋白(LMP-1)染色,以判断标本是否有HPV16及EBV感染,计算病毒检出率。比较不同病理类型乳腺癌的病毒检出率及比较PCR、免疫组织化学两种方法对乳腺组织标本病毒感染的检出率有无差异采用χ2检验。不同病理类型的乳腺癌标本中HPV16及EBV阳性细胞率的比较选用方差分析以及Bonferroni两两比较。结果 PCR结果显示:HPV16病毒检出率在乳腺癌标本为44.44%(40/90),乳腺纤维瘤标本为5%(1/20),正常乳腺组织为0;EBV的病毒检出率在乳腺癌标本中为43.33%(39/90),乳腺纤维瘤标本及正常乳腺组织均为0。在不同病理类型乳腺癌中,HPV16和EBV的病毒检出率差异均无统计学意义(χ2=1.238,P=0.539;χ2=1.867,P=0.393)。免疫组织化学结果显示:HPV16病毒检出率在乳腺癌标本为42.22%(38/90),乳腺纤维瘤标本为5%(1/20),正常乳腺组织为0;EBV病毒检出率在乳腺癌标本为42.22%(38/90),乳腺纤维瘤标本及正常乳腺组织均为0。有HPV16病毒感染的乳腺癌组织标本中,HPV16阳性细胞率在浸润性导管癌为(29.78±0.38)%,浸润性小叶癌为(28.31±0.53)%,原位癌为(51.83±0.65)%,3组比较差异有统计学意义(F=537.779,P=0.000);有EBV病毒感染的乳腺癌组织标本中,EBV阳性细胞率分别为(29.73±0.51)%、(28.14±0.65)%及(51.11±0.68)%,3组比较差异有统计学意义(F=427.771,P=0.000);原位癌标本中,HPV16和EBV的阳性细胞率均显著高于其他两种病理类型的乳腺癌(P均=0.000)。两种方法对乳腺癌标本HPV16及EBV的检出率差异不具有统计学意义(χ2=0.090,P=0.764;χ2=0.023,P=0.880)。结论 HPV16和EBV两种病毒的感染与乳腺癌的发生可能有一定的关系,其感染程度可能与乳腺癌的病理类型有关。

【Abstract】 Objective To explore the expression of human papilloma virus 16( HPV16) and EpsteinBarr virus( EBV) in different pathological types of breast cancer and breast benign lesions. Methods We analyzed the samples from 90 cases of different pathological types of breast cancer( including 40 cases of invasive ductal carcinoma,30 invasive lobular carcinoma and 20 carcinoma in situ),20 cases of mammary fibroma and 10 cases of normal breast tissues. All specimens were collected from the patients treated in our hospital from June 2013 to June 2014. PCR was performed to amplify E6 gene site of HPV16 and the repeated sequence Bam HIW of EBV. The expressions of HPV16 and latent membrane protein 1( LMP-1) of EBV were detected by immunohistochemical staining to determine whether existed HPV16 or EBV infections,and the positive rate was calculated accordingly. The detection rate of virus between different pathological types of breast cancer and the detection rate of virus between PCR detection and immunohistochemistry was compared by χ2test; the proportion of HPV16 positive cells and the proportion of EBV positive cells among different pathological types of breast cancer was compared by analysis of variance and Bonferroni pairwise comparison. Results PCR showed that HPV16 detection rate was 44. 44%( 40 /90) in breast cancer,5%( 1 /20) in mammary fibroma and 0 in normal breast tissues; EBV detection rate was 43. 33%( 39 /90) in breast cancer,0 in mammary fibroma and normal breast tissues; there were no statistically significant difference in the detection rate of HPV16 and EBV between different pathological types of breast cancer( χ2= 1. 238,P = 0. 539; χ2= 1. 867,P = 0. 393). Immunohistochemistry showed that HPV16 detection rate was 42. 22%( 38 /90) in breast cancer,5%( 1 /20) in mammary fibroma and 0 in normal breast tissues; EBV detection rate was 42. 22%( 38 /90) in breast cancer,0 in mammary fibroma and normal breast tissues. The proportion of HPV16 positive cells was( 29. 78 ± 0. 38) % in invasive ductal carcinoma,( 28. 31 ± 0. 53) % in invasive lobular carcinoma,( 51. 83 ±0. 65) % in carcinoma in situ,suggesting a significant difference( F = 537. 779,P = 0. 000). The proportion of EBV positive cells was( 29. 73 ± 0. 51) %,( 28. 14 ± 0. 65) % and( 51. 11 ± 0. 68) % respectively,which was significantly different( F = 427. 771,P = 0. 000); the sample of carcinoma in situ showed the higher proportion of HPV16 and EBV positive cells,compared with other two pathological types( all P = 0. 000). The detection rates of HPV16 or EBV by PCR and immunohistochemistry in breast cancer specimens were not significantly different( χ2= 0. 090,P = 0. 764; χ2= 0. 023,P = 0. 880). Conclusion The infection of HPV16 and EBV may be related to the occurrence of breast cancer, and the infection degree is probably related to the pathological types of breast cancer.

【基金】 国家自然科学基金资助项目(81272899;81172510);第四军医大学西京医院学科助推基金(XJZT12Z07);西安市科技计划项目[SF1323(3)];陕西省社会发展攻关计划项目(2013K12-03-03)
  • 【文献出处】 中华乳腺病杂志(电子版) ,Chinese Journal of Breast Disease(Electronic Edition) , 编辑部邮箱 ,2014年05期
  • 【分类号】R737.9
  • 【被引频次】2
  • 【下载频次】92
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