High-risk human papillomavirus (HPV) DNA sequences in metaplastic breast carcinomas of Mexican women

Roberto Herrera-Goepfert,Alfredo Amador-Molina,Luis F Oñate-Ocaña,Adela Carrillo-García,Rita Sotelo-Regil Hallmann,Marcela Lizano-Soberón,Teresa Vela-Chávez

doi:10.1186/1471-2407-13-445

Roberto Herrera-Goepfert, Alfredo Amador-Molina + Show 5 more

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https://doi.org/10.1186/1471-2407-13-445

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Abstract

BackgroundMetaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma.MethodsMastectomy specimens from patients harboring metaplastic breast carcinoma, as defined by the World Health Organization (WHO), and who attended the Instituto Nacional de Cancerologia in Mexico City, were retrieved from the files of the Department of Pathology accumulated during a 16-year period (1995–2008). Demographic and clinical information was obtained from patients’ medical records. DNA was extracted from formalin-fixed, paraffin-embedded tumors and HPV type-specific amplification was performed by means of Polymerase chain reaction (PCR). Quantitative Real-time (RT) PCR was conducted in HPV positive cases. Statistically, the association of continuous or categorical variables with HPV status was tested by the Student t, the Chi square, or Fisher’s exact tests, as appropriate.ResultsHigh-risk HPV DNA was detected in eight (40%) of 20 metaplastic breast carcinomas: seven (87.5%) HPV-16 and one (12.5%) HPV-18. Mean age of patients with HPV-positive cases was 49 years (range 24–72 years), the same as for HPV-negative cases (range, 30–73 years). There were not striking differences between HPV + and HPV– metaplastic carcinomas regarding clinical findings. Nearly all cases were negative for estrogen, progesterone and Human epidermal growth factor receptor 2 (HER2), but positive for Epidermal growth factor receptor (EGFR).ConclusionsHigh-risk HPV has been strongly associated with conventional breast carcinomas, although the subtle mechanism of neoplastic transformation is poorly understood. In Mexican patients, the prevalence of HPV infection among metaplastic breast carcinomas is higher than in non-metaplastic ones, as so the HPV viral loads; notwithstanding, HPV viral loads show wide variation and remain even lower than cervical and other non-cervical carcinomas, making it difficult to assume that HPV could play a key role in breast carcinogenesis. Further studies are warranted to elucidate the meaning of the presence of high-risk HPVDNA in breast carcinomas.

Highlights

Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas
High-risk Human papillomavirus (HPV) has been strongly advocated as a potential carcinogenic agent since 1992 by Di Lonardo et al [10], who reported the presence of HPV-16 Deoxyribonucleic acid (DNA) in nearly 30% of ductal breast carcinomas, by means of Polymerase chain reaction (PCR)
We previously suggested that the presence of HPV DNA sequences in breast tissues and breast carcinomas could be related with changes in the level of expression of integrins, with that of the α-6 integrin [20], and of Heparan sulfate proteoglycans (HSPG) [42], which are putative candidates for HPV cell receptors [43]

Summary

Introduction

Metaplastic carcinoma, an uncommon subtype of breast cancer, is part of the spectrum of basal-like, triple receptor-negative breast carcinomas. The present study examined 20 surgical specimens of metaplastic breast carcinomas, for the presence of high-risk Human papillomavirus (HPV), which is suspected to be a potential carcinogenic agent for breast carcinoma. According to the transcriptional profiling-based new molecular classification of breast carcinomas, basal-like carcinomas are considered a subtype of triple receptor- negative cancers, the other subtype comprising the normal breast-like carcinoma [7]. High-risk Human papillomavirus (HPV) has been strongly advocated as a potential carcinogenic agent since 1992 by Di Lonardo et al [10], who reported the presence of HPV-16 Deoxyribonucleic acid (DNA) in nearly 30% of ductal breast carcinomas, by means of Polymerase chain reaction (PCR). In a series of 27 pure or metaplastic squamous cell carcinomas of the mammary gland, Grenier et al [11] found HPV DNA in two of 14 (7.4%) metaplastic breast carcinomas

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