Oncogenic role of JC virus in lung cancer.
The JC virus (JCV) infects a large proportion of the population world wide and can cause progressive multifocal leucoencephalopathy in the context of immunodeficiency. Recent reports provide evidence that it may also be oncogenic. Here, JCV was examined by targeting its T-antigen in lung carcinomas (n=103) and normal lung tissues (n=18) by nested-PCR followed by Southern blot, real-time PCR, immunohistochemistry, in situ hybridization and in situ PCR. Additionally, expression of Ki-67, caspase-3, beta-catenin, p53, and Rb was analysed by immunohistochemistry on tissue microarrays of lung carcinomas. Copy numbers of JCV were compared with clinicopathological features. Normal lung tissue was positive significantly less frequently, and contained a lower copy number of JCV than lung carcinomas (p<0.05), and copies were lower in lung adenocarcinomas than in squamous, small or large cell carcinomas (p<0.05). In situ PCR and immunolabelling revealed JCV positivity in the nuclei of lung carcinoma cells. The JCV copy number correlated closely with sex, and expression of Ki-67 and membrane beta-catenin (p<0.05), but not with age, tumour size, pleural invasion, lymph node metastasis, expression of caspase-3, cytoplasmic beta-catenin, p53 or Rb, prognosis, smoking or cancer family history (p>0.05). Age and UICC staging were independent prognostic factors for lung carcinoma patients. These data suggest that JCV may be involved in lung carcinogenesis, especially in tumour types other than adenocarcinoma. Lung carcinomas with higher JCV copy numbers display high proliferation and down-regulation of cell adhesion mediated by membrane beta-catenin.
Zheng
H
H
Department of Diagnostic Pathology, Graduate School of Medicine and Pharmaceutical Science, University of Toyama, Toyama, Japan.
Abdel Aziz
H O
HO
Nakanishi
Y
Y
Masuda
S
S
Saito
H
H
Tsuneyama
K
K
Takano
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000235:genetics; D015139:Blotting, Southern / Q000379:methods; D002277:Carcinoma / Q000473:pathology / Q000821:virology*; D018287:Carcinoma, Large Cell / Q000473:pathology / Q000821:virology; D018288:Carcinoma, Small Cell / Q000473:pathology / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D017403:In Situ Hybridization; D007577:JC Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D008175:Lung Neoplasms / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D009858:Oncogenic Viruses; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
D000957:Antigens, Viral, Tumor; D004279:DNA, Viral; D012333:RNA, Messenger