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      Koilocytes indicate a role for human papilloma virus in breast cancer

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          Abstract

          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.

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          Most cited references31

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          Oral sexual behaviors associated with prevalent oral human papillomavirus infection.

          Oral human papillomavirus (HPV) infection is a cause of oropharyngeal cancer. We investigated whether sexual behaviors that elevated the odds of oropharyngeal cancer developing in a case-control study similarly elevated the odds of oral HPV infection developing among control patients. HPV infection was detected in 4.8% of 332 control patients from an outpatient clinic and in 2.9% of 210 college-aged men (age range, 18-23 years). Among control patients, the odds of infection developing independently increased with increases in the lifetime number of oral (P = .007, for trend) or vaginal sex partners (P = .003, for trend). Among college-aged men, the odds of oral HPV infection developing increased with increases in the number of recent oral sex partners (P = .046, for trend) or open-mouthed kissing partners (P = .023, for trend) but not vaginal sex partners. Oral sex and open-mouthed kissing are associated with the development of oral HPV infection.
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            Human papillomavirus detected in female breast carcinomas in Japan

            To investigate the aetiological role of human papillomavirus (HPV) in breast cancer, we examined the presence, genotype, viral load, and physical status of HPV in 124 Japanese female patients with breast carcinoma. Human papillomavirus presence was examined by PCR using SPF10 primers, and primer sets targeting the E6 region of HPV-16, -18, and -33. The INNO-LiPA HPV genotyping kit was used to determine genotype. Human papillomavirus DNA was detected in 26 (21%) breast carcinomas. The most frequently detected HPV genotype was HPV-16 (92%), followed by HPV-6 (46%), HPV-18 (12%), and HPV-33 (4%). In 11 normal epithelium specimens adjacent to 11 HPV-16-positive carcinomas, 7 were HPV-16-positive. However, none of the normal breast tissue specimens adjacent to HPV-negative breast carcinomas were HPV-positive. The real-time PCR analysis suggested the presence of integrated form of viral DNA in all HPV-16-positive samples, and estimated viral load was low with a geometric mean of 5.4 copies per 104 cells. In conclusion, although HPV DNA was detected in 26 (21%) breast carcinomas and, in all HPV-16-positive cases, the HPV genome was considered integrated into the host genome, their low viral loads suggest it is unlikely that integrated HPV is aetiologically involved in the development of Japanese breast carcinomas that we examined.
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              Presence of papillomavirus sequences in condylomatous lesions of the mamillae and in invasive carcinoma of the breast

              Background Viruses including Epstein–Barr virus (EBV), a human equivalent of murine mammary tumour virus (MMTV) and human papillomavirus (HPV) have been implicated in the aetiology of human breast cancer. We report the presence of HPV DNA sequences in areolar tissue and tumour tissue samples from female patients with breast carcinoma. The presence of virus in the areolar–nipple complex suggests to us a potential pathogenic mechanism. Methods Polymerase chain reaction (PCR) was undertaken to amplify HPV types in areolar and tumour tissue from breast cancer cases. In situ hybridisation supported the PCR findings and localised the virus in nipple, areolar and tumour tissue. Results Papillomavirus DNA was present in 25 of 29 samples of breast carcinoma and in 20 of 29 samples from the corresponding mamilla. The most prevalent type in both carcinomas and nipples was HPV 11, followed by HPV 6. Other types detected were HPV 16, 23, 27 and 57 (nipples and carcinomas), HPV 20, 21, 32, 37, 38, 66 and GA3-1 (nipples only) and HPV 3, 15, 24, 87 and DL473 (carcinomas only). Multiple types were demonstrated in seven carcinomas and ten nipple samples. Conclusions The data demonstrate the occurrence of HPV in nipple and areolar tissues in patients with breast carcinoma. The authors postulate a retrograde ductular pattern of viral spread that may have pathogenic significance.
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                Author and article information

                Journal
                Br J Cancer
                British Journal of Cancer
                Nature Publishing Group
                0007-0920
                1532-1827
                22 September 2009
                13 October 2009
                20 October 2009
                : 101
                : 8
                : 1351-1356
                Affiliations
                [1 ]School of Biotechnology and Biomolecular Sciences, University of New South Wales Sydney, New South Wales, Australia
                Author notes
                [* ]Author for correspondence: james.lawson@ 123456unsw.edu.au
                Article
                6605328
                10.1038/sj.bjc.6605328
                2768439
                19773762
                33a9a31c-88d9-4225-b627-4790aa165a24
                Copyright 2009, Cancer Research UK
                History
                : 01 July 2009
                : 14 August 2009
                : 24 August 2009
                Categories
                Molecular Diagnostics

                Oncology & Radiotherapy
                koilocytosis,aetiology,expression,breast cancer,hpv e6 oncoprotein,hpv
                Oncology & Radiotherapy
                koilocytosis, aetiology, expression, breast cancer, hpv e6 oncoprotein, hpv

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