摘要
目的通过检测乳腺黏液癌（以M表述）及浸润性导管癌（符合基底细胞样癌分子分型诊断标准：以D-B表述）标本中乳腺癌阻抑蛋白1关联RING蛋白1（BRCA1-associated RING domain,BARD1）剪切变异体表达水平的差异,结合术后随访结果,探讨BARD1基因在乳腺癌中可能的临床意义。方法以本院乳腺中心标本库储存的43例M标本及39例D-B标本提取的目的基因进行RT-PCR,对相应病例石蜡包埋组织切片进行病理免疫组织化学检测;患者术后每半年随访1次,记录无病生存期（disease free survival,DFS）及总生存期（overall survival,OS）;分析BARD1基因的临床意义。结果在所有标本中共发现4种BARD1基因的转录产物：全长BARD1基因（full lenth,Fl）,剪切变异体γ、δ和ε,其中Fl在所有组织中均有表达,剪切变异体δ和ε在M中的阳性表达率低于D-B（P〈0.005）;免疫组织化学检测发现在D-B中BARD1蛋白阳性细胞比率显著高于M（P〈0.005）,两种癌组织中蛋白均异位表达于细胞质中;BARD1剪切变异体的阳性表达与乳腺癌预后差的因素有关（P〈0.05）。研究病例术后随访36~70个月,单因素分析发现,剪切变异体ε阳性表达与乳腺癌术后无病生存期及总生存期缩短均显著相关（P〈0.05）。结论 BARD1剪切变异体在不同类型乳腺癌中的表达存在差异;与正常组织细胞相比,BARD1剪切变异体异位表达在肿瘤细胞质中;剪切变异体δ和ε与乳腺癌预后差的因素相关,并且剪切变异体ε阳性表达的患者无病生存期及总生存期均显著缩短。因此BARD1剪切变异体的异常表达或许影响乳腺癌的生物学行为,进而影响乳腺癌的预后。
Objective To explore the potential relationship between abberant expression of BRCA1 associated RING domain 1（BARD1） and the prognosis factors of mucinous carcinoma（abbreviated to M） and invasive ductal carcinoma with basal like characteristic（abbreviated to D-B） by detecting the expression of BARD1 isoforms in breast carcinomatous tissue specimen.Method The expression of BARD1 isoforms in 43 M tissues,and 39 D-B tissues was detected by reverse transcription polymerase chain reaction（RT-PCR） and immunohistochemistry.Following-up was taken every 6 months after operation,recording DFS and OS.Result There were four transcriptive products of BARD1 found in all these candidates,named full lenth（Fl）,isoform γ,δ and ε.Fl was expressed in all cases.The positive rate of isoform δ and ε was lower in M tissues than that in D-B tissues（P〈0.05）.The concentration of BARD1 protein detected by immunohistochemistry was higher in D-B breast cancer than that in M candidates（P〈0.05）,and BARD1 protein was abnormally located in plasma in cancer cells.By the univariate analysis,there was significant correlation between isoform ε positive and shortened DFS and OS（P〈0.05）.Conclusion The expression of BARD1 varied considerably between different pathologic types of breast cancer.The expression of BARD1 isoforms was associated with the poor prognostic factors of breast cancer,and they abnormally located in the plasma of tumor cells.These data suggest that the aberrant expression of BARD1 might influence the physiologic function of cells.Some BARD1 isoforms might be poor prognostic factors for breast cancers.
出处
《中国医刊》
CAS
2016年第3期66-72,共7页
Chinese Journal of Medicine
基金
国家科技支撑计划课题(2014BAI08B00
2014BAI08B03)
