Presence of high risk HPV DNA but indolent transcription of E6/E7 oncogenes in invasive ductal carcinoma of breast.
OBJECTIVE
The causative role of high risk human papillomavirus (HR-HPV) in breast cancer development is controversial, though a number of reports have identified HR-HPV DNA in breast cancer specimens. Nevertheless, most studies to date have focused primarily on viral DNA rather than the viral transcription. The aim of this study was to investigate the presence of HR-HPV in breast cancer tissues at HPV DNA level and HPV oncogenes mRNA level by in situ hybridization (ISH).


METHODS
One hundred and forty six (146) cases of breast invasive ductal carcinoma(IDC) and 83 cases of benign breast lesions were included in the study. Type specific oligonucleotide probes were used for the DNA detection of HPV 16,18 and 58 by ISH. HR-HPV oncogenes mRNA was assayed by novel RNAscope HR-HPV HR7 assay ISH. p16 protein expression was evaluated by immunohistochemistry (IHC).


RESULTS
HR-HPV 16,18 and 58 DNA were detected in 52 out of 146 (35.6%) IDC and in 3 out of 83 (3.6%) benign breast lesions by ISH. The HR-HPV mRNAs was detected only in a few specimens with strong HPV DNA positivity(4/25) in a few scattered cancer cells with very weak punctate nuclear and/or cytoplasmic staining. p16 over-expression did not correlate with the HPV DNA positive breast cancer samples(17/52 HPVDNA+ vs 28/94 HPV DNA-, p=0.731).


CONCLUSIONS
HR-HPVs certainly exist in breast cancer tissue with less active transcription, which implies that the causal role of HPV in breast cancer development need further study.
Center of Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, #227 YanTaXiLu, Xi'an, 710061, China.
Depu
D
Wang
Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China.
Ling
L
Fu
Institute of Basic Medical Sciences, Khyber Medical University, Peshawar, 25000, Pakistan.
Walayat
W
Shah
Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China.
Jingwen
J
Zhang
Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China.
Yan
Y
Yan
Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China.
Xinhong
X
Ge
Cancer Center of the First Affiliated Hospital, Xi'an Jiaotong University, #227 YanTaXiLu, Xi'an, 710061, China.
Jianjun
J
He
Institute of Cancer Research, School of Basic Medical Science, Xi'an Jiaotong University, #76 YanTaXiLu, Xi'an, 710061, China. Electronic address: wangyili@mail.xjtu.edu.cn.
Yili
Y
Wang
Center of Translational Medicine, The First Affiliated Hospital, Xi'an Jiaotong University, #227 YanTaXiLu, Xi'an, 710061, China. Electronic address: lixu56@mail.xjtu.edu.cn.
Xu
X
Li
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000821:virology*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000473:pathology / Q000821:virology*; D004279:DNA, Viral / Q000235:genetics*; D005260:Female; D061809:Human Papillomavirus DNA Tests; D006801:Humans; D008875:Middle Aged; D009857:Oncogenes / Q000235:genetics*; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000821:virology
D004279:DNA, Viral
Breast cancer; HPV; HPV mRNA transcript; High risk human papillomavirus; RNA-ISH