Long non-coding RNA chromogenic in situ hybridisation signal pattern correlation with breast tumour pathology.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
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.
Zhouwei
Z
Zhang
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.
Donald L
DL
Weaver
Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont, USA.
Daniel
D
Olsen
Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, Vermont, USA.
James
J
deKay
Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
Zhihua
Z
Peng
University of Vermont Cancer Center, Burlington, Vermont, USA Biostatistics Unit, University of Vermont College of Medicine, Burlington, Vermont, USA.
Takamaru
T
Ashikaga
Department of Pathology and Laboratory Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA University of Vermont Cancer Center, Burlington, Vermont, USA.
Mark F
MF
Evans
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics* / Q000473:pathology; D002863:Chromogenic Compounds; D005260:Female; D006801:Humans; D017403:In Situ Hybridization / Q000379:methods*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D062085:RNA, Long Noncoding / Q000235:genetics*
D014408:Biomarkers, Tumor; D002863:Chromogenic Compounds; C094335:H19 long non-coding RNA; C561566:HOTAIR long untranslated RNA, human; C449939:KCNQ1OT1 RNA; D062085:RNA, Long Noncoding
BREAST CANCER; IN SITU HYBRIDISATION; TUMOUR MARKERS