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Oncogenic role of JC virus in lung cancer
Author(s) -
Zheng H,
Aziz HO Abdel,
Nakanishi Y,
Masuda S,
Saito H,
Tsuneyama K,
Takano Y
Publication year - 2007
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2188
Subject(s) - pathology , carcinogenesis , lung cancer , biology , immunohistochemistry , adenocarcinoma , tissue microarray , lung , in situ hybridization , population , cancer research , cancer , medicine , gene expression , gene , biochemistry , genetics , environmental health
The JC virus (JCV) infects a large proportion of the population world wide and can cause progressive mulitifocal 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, β‐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 β‐catenin ( p < 0.05), but not with age, tumour size, pleural invasion, lymph node metastasis, expression of caspase‐3, cytoplasmic β‐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 β‐catenin. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.