?(Fig.1e),1e), while the same approach led to a strong labelling of nasopharyngeal carcinoma cell nuclei (Fig. results indicate that breast carcinoma is not an EBV-associated tumour. strong class=”kwd-title” Keywords: breast carcinoma, EpsteinCBarr computer virus, immunohistology, em in situ /em hybridisation Introduction EpsteinCBarr computer virus (EBV) is usually a ubiquitous human -herpes computer virus infecting more than 90% of the adult populace worldwide. EBV is usually associated with several malignancies (e.g. Burkitt lymphoma, Hodgkin lymphoma and nasopharyngeal carcinoma) and thus has been classified as a group 1 carcinogen [1]. Several studies have recently hinted at a possible role for EBV in the pathogenesis of breast carcinoma, which represents the Rabbit polyclonal to SCP2 most common carcinoma of females in the Western world [2,3]. If substantiated, this would have potential implications for the prevention and treatment of breast malignancy. Immunotherapeutic strategies based on EBV-specific cytotoxic T cells are currently being developed for the treatment of EBV-positive Hodgkin lymphoma and nasopharyngeal carcinoma, and they could potentially also be applied to EBV-associated breast carcinoma [4-6]. Against this background, the possibility that EBV may be involved in the pathogenesis of breast carcinoma has received great attention. The first studies addressing this issue focused on medullary carcinomas since these are morphologically much like nasopharyngeal carcinoma. However, these studies consistently failed to detect EBV in medullary carcinomas PYR-41 using numerous techniques [7-9]. The possibility that invasive ductal and invasive lobular breast carcinomas might be EBV-associated was raised by Labrecque and coworkers [2], triggering a large number of followup studies. However, the results and conclusions have been highly variable. It is generally accepted that EBV DNA can be detected PYR-41 in up to 50% of breast carcinomas using the PCR [2,3,10-13]. Results obtained with other methods are more difficult to reconcile. Studies using immunohistochemistry or em in situ /em hybridisation have confirmed the presence of the computer virus only in a proportion of the PCR-positive cases [2,3]. Moreover, EBV was detected only in a subset of tumour cells in some reports, raising questions regarding the possible role of the computer virus in breast carcinogenesis [10-12]. Using em in situ /em hybridisation, focal expression of the small EBV-encoded RNAs (EBERs) was detected in tumour cells of some breast PYR-41 carcinomas [11,12], while other studies have exhibited a complete absence of EBER expression from breast carcinomas [14,15]. Since the EBERs are expressed in all established EBV-associated tumours [1], the latter finding would appear to argue against an association of EBV with breast carcinomas. Nevertheless, expression of the EBV-encoded nuclear antigen 1 (EBNA1) has been detected by immunohistochemistry in a proportion of cases, and it has been argued that an EBER-negative form of EBV contamination may be prevalent in breast carcinomas [3,11,16]. The evidence regarding a possible association of EBV with breast carcinoma is thus controversial and, in view of the high incidence of this tumour, requires clarification. Before undertaking a study of breast carcinoma, we felt it was important to establish criteria for the definition of EBV-associated tumours. The study of DNA extracts by PCR is clearly not satisfactory since it leaves unanswered the question PYR-41 of the cellular source of any viral genomes detected. This concern also applies to Southern blot hybridisation, although determination of viral clonality is possible with this method, thus allowing conclusions regarding the clonality of the cell populace harbouring the computer virus [17]. Unequivocal localisation of the computer virus is best achieved by em in situ /em techniques. Immunohistochemical methods are available for the PYR-41 detection of viral proteins in paraffin sections. However, some of these are not consistently expressed in latent EBV contamination [1]. Only EBNA1 is usually expressed in all known forms of viral latency, yet the antibodies available for the detection of this protein usually produce only poor staining. A lack of detectable EBNA1 expression thus cannot.