Epstein-Barr Virus is Associated With Aggressive Subtypes of Invasive Ductal Carcinoma of Breast (Her2+/ER- and Triple Negative) and With Nuclear Expression of NFκB p50

Background: A growing body of evidence suggests a possible role for Epstein-Barr virus (EBV) in the pathogenesis of a subset of breast cancers, with many ofthese studies highlighting an increased association between EBV and aggressiveforms of breast carcinoma. This study aimed to further investigate this issue byassessing the possible association between EBV and the Her2+/ER- and Triplenegative sub types of invasive ductal carcinoma (IDC). Methods: An immunohistochemical marker for EBV (Epstein-Barr virusnuclear antigen 1 (EBNA1) clone E1-2.5) was applied to tissue micro arraysections. The tissue micro array's contained 58 cases of Her2+/ER- IDC, 57 cases oftriple negative IDC and 67 cases of luminal like IDC. Each case was scored aspositive or negative for nuclear expression of EBNA1 in tumour cells usingstandard light microscopy. Clinical and pathological details where noted for eachcase, as was the nuclear expression of NFκB p50. Results: EBV infection was apparent in 43.2% of all cases. By subtype EBVwas evident in 31 (57.4%) Her2+/ER- cases, 28 (49.1%) triple negative cases, and14 (24.1%) luminal like cases; with a significant association being noted betweenthe Her2+/ER- and triple negative cases and EBV infection (P 0.001). Thisassociation was primarily linked with ER negativity, Her2 status showed nosignificant association with EBV infection. There were no significant associationswith other clinical and pathological characteristics. Of the 53 cases demonstratingNFκB p50 nuclear staining, 37 (69.8%) were also infected by EBV (P <0.001). Conclusion: This study provides evidence that EBV is associated withaggressive subtypes of IDC (Her2+/ER- and triple negative) as well as providingevidence for a link between EBV and NFκB p50 nuclear expression, although thenature of these associations remains unclear.

Epstein-Barr Virus is Associated With Aggressive Subtypes of Invasive Ductal Carcinoma of Breast (Her2+/ER- and Triple Negative) and With Nuclear Expression of NFκB p50 Keywords:

Epstein-Barr virus , breast cancer , estrogen receptor , Her2 receptor , nuclear factor κB