Zhang Zhouwei, Weaver Donald L, Olsen Daniel, deKay James, Peng Zhihua, Ashikaga Takamaru, Evans Mark F
Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA Laboratory of Cancer Epigenetics, Van Andel Research Institute, NE Grand Rapids, Michigan, USA.
Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont, USA University of Vermont Cancer Center, Burlington, Vermont, USA.
J Clin Pathol. 2016 Jan;69(1):76-81. doi: 10.1136/jclinpath-2015-203275. Epub 2015 Aug 31.
Long non-coding RNAs (lncRNAs) are potential biomarkers for breast cancer risk stratification. LncRNA expression has been investigated primarily by RNA sequencing, quantitative reverse transcription PCR or microarray techniques. In this study, six breast cancer-implicated lncRNAs were investigated by chromogenic in situ hybridisation (CISH).
Invasive breast carcinoma (IBC), ductal carcinoma in situ (DCIS) and normal adjacent (NA) breast tissues from 52 patients were screened by CISH. Staining was graded by modified Allred scoring.
HOTAIR, H19 and KCNQ1OT1 had significantly higher expression levels in IBC and DCIS than NA (p<0.05), and HOTAIR and H19 were expressed more strongly in IBC than in DCIS tissues (p<0.05). HOTAIR and KCNQ101T were expressed in tumour cells; H19 and MEG3 were expressed in stromal microenvironment cells; MALAT1 was expressed in all cells strongly and ZFAS1 was negative or weakly expressed in all specimens.
These data corroborate the involvement of three lncRNAs (HOTAIR, H19 and KCNQ1OT1) in breast tumourigenesis and support lncRNA CISH as a potential clinical assay. Importantly, CISH allows identification of the tissue compartment expressing lncRNA.
长链非编码RNA（lncRNA）是乳腺癌风险分层的潜在生物标志物。lncRNA表达主要通过RNA测序、定量逆转录PCR或微阵列技术进行研究。在本研究中，通过显色原位杂交（CISH）对六种与乳腺癌相关的lncRNA进行了研究。
采用CISH对52例患者的浸润性乳腺癌（IBC）、原位导管癌（DCIS）和正常相邻（NA）乳腺组织进行筛选。染色采用改良的Allred评分法进行分级。
HOTAIR、H19和KCNQ1OT1在IBC和DCIS中的表达水平显著高于NA（p<0.05），且HOTAIR和H19在IBC中的表达强于DCIS组织（p<0.05）。HOTAIR和KCNQ101T在肿瘤细胞中表达；H19和MEG3在基质微环境细胞中表达；MALAT1在所有细胞中均强烈表达，ZFAS1在所有标本中均为阴性或弱表达。
这些数据证实了三种lncRNA（HOTAIR、H19和KCNQ1OT1）参与乳腺癌的发生，并支持lncRNA CISH作为一种潜在的临床检测方法。重要的是，CISH能够识别表达lncRNA的组织区域。
