Koilocytes indicate a role for human papilloma virus in breast cancer

British Journal of Cancer (2009) 101, 1351 1356& 2009 Cancer Research UK All rights reserved 0007 0920/09 $32.00

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Koilocytes indicate a role for human papilloma virus in breast cancer

JS Lawson*,1, WK Glenn1, B Heng1, Y Ye1, B Tran1, L Lutze-Mann1 and NJ Whitaker1

1School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia

BACKGROUND: High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer. The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites. Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are epithelial cells characterised by perinuclear haloes surrounding condensed nuclei and are commonly present in cervical intraepithelial neoplasia. Koilocytosis is accepted as pathognomonic (characteristic of a particular disease) of HPV infection. The aim of this investigation is to determine whether putative koilocytes in normal and malignant breast tissues are because of HPV infection.

METHODS: Archival formalin-fixed normal and malignant breast specimens were investigated by histology, in situ PCR with confirmation of the findings by standard PCR and sequencing of the products, plus immunohistochemistry to identify HPV E6 oncoproteins.

RESULTS: human papilloma virus-associated koilocytes were present in normal breast skin and lobules and in the breast skin and cancer tissue of patients with ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDCs).

INTERPRETATION: As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.

British Journal of Cancer (2009) 101, 13511356. doi:http://dx.doi.org/10.1038/sj.bjc.6605328

Web End =10.1038/sj.bjc.6605328 http://www.bjcancer.com

Web End =www.bjcancer.com Published online 22 September 2009& 2009 Cancer Research UK

Keywords: breast cancer; HPV; aetiology; expression; HPV E6 oncoprotein; koilocytosis

MolecularDiagnostics

High-risk human papilloma viruses (HPVs) are candidates as causal viruses in breast cancer (Lawson et al, 2006). Human papilloma virus high-risk types 16, 18 and 33 have been identified in breast cancers from 15 widely different populations (Lawson et al, 2006). The scientific challenge is to determine whether HPVs are causal and not merely passengers or parasites.

Studies of HPV-related koilocytes in breast cancer offer an opportunity to address this crucial issue. Koilocytes are commonly present in cervical intraepithelial neoplasia. They are epithelial...