Epstein-Barr virus in breast carcinoma and in triple negative cases impact on clinical outcomes

Saoussen Mekrazi; Imen Kallel; Dhouha Jamai; Mariem Yengui; Abdelmajid Khabir; Radhouane Gdoura

doi:10.1016/j.prp.2023.154484

Epstein-Barr virus in breast carcinoma and in triple negative cases impact on clinical outcomes

Pathol Res Pract. 2023 May:245:154484. doi: 10.1016/j.prp.2023.154484. Epub 2023 Apr 25.

Authors

Saoussen Mekrazi¹, Imen Kallel², Dhouha Jamai³, Mariem Yengui¹, Abdelmajid Khabir⁴, Radhouane Gdoura¹

Affiliations

¹ Research Laboratory of Environmental Toxicology-Microbiology and Health (LR17ES06), Faculty of Sciences, University of Sfax, 3038 Sfax, Tunisia.
² Research Laboratory of Environmental Toxicology-Microbiology and Health (LR17ES06), Faculty of Sciences, University of Sfax, 3038 Sfax, Tunisia. Electronic address: kallel1imen@yahoo.fr.
³ Research Laboratory of Bioresources, Integrative Biology and Valorization LR14ES06, Higher Institute of Biotechnology of Monastir, University of Monastir, Avenue Tahar Hadded, BP 74, 5000 Monastir, Tunisia.
⁴ Department of Anatomopathology and Cytology - Habib BOURGUIBA Hospital, Medenine, Tunisia.

PMID: 37116366
DOI: 10.1016/j.prp.2023.154484

Abstract

Background: The contribution of viral infection in tumors pathogenesis has currently attracted attention. Epstein-Barr virus is an infectious agent involved in numerous human malignancies, including breast cancer. Although, their prognostic impact in breast tumor is rarely investigated. Therefore, we sought in our study to evaluate the prevalence of EBV in Tunisian breast carcinoma and to examine their potential association with clinicopathological features and overall survival.

Methods: Our retrospective study included 100 formalin fixed paraffin embedded samples from Tunisian breast carcinoma. EBV infection was evaluated by immunohistochemical analysis, using monoclonal antibody against latent membrane protein 1 (LMP-1) and polymerase chain reaction. A subset of PCR positive specimens was subjected to in situ hybridization for the detection of EBER expression. Biomarker's expression was evaluated by immunohistochemistry method. Statistical analysis was also explored.

Results: The expression status of ER, PR and HER2 was 81%, 71.4% and 33.7% respectively. The triple negative profile was present in 10.84% of cases. LMP-1 expression was negative in all breast cancer specimens. PCR assay showed that 44% of patients were positive for EBV genome. None of the 15 PCR positive cases showed positive results for EBV by ISH. According to the molecular phenotype, there was a statistically significant difference in EBV DNA prevalence between breast cancer subgroups including TN (67%), Lum B (64%), HER2 + (50%) and Lum A (30%). Bivariate analysis showed that EBV DNA was significantly associated with HER2 + (p = 0.035), tumor size (p = 0.018) and high SBR grade (p = 0.009). Multiple logistic regression analysis confirms the positive correlation of EBV with tumor size (p = 0.048) and SBR grade (p = 0.042). Kaplan-Meier analysis showed that patients with EBV+ had significantly shorter overall survival than those with EBV- (p = 0.032).

Conclusions: Our study demonstrated the presence of EBV DNA in Tunisian breast carcinoma. EBV DNA was associated with aggressive features and poor overall survival. Further investigations will be required in large samples size to clarify the potential role of EBV in breast tumor progression.

Keywords: Breast carcinoma; Epstein–Barr virus; Overall survival; Prognosis; TNBC.

MeSH terms

Breast Neoplasms* / pathology
DNA
Epstein-Barr Virus Infections* / diagnosis
Female
Herpesvirus 4, Human / genetics
Humans
Retrospective Studies
Viral Matrix Proteins / genetics
Viral Matrix Proteins / metabolism

Substances

DNA
Viral Matrix Proteins