Research Laboratory of Environmental Toxicology-Microbiology and Health (LR17ES06), Faculty of Sciences, University of Sfax, 3038 Sfax, Tunisia.
Research Laboratory of Environmental Toxicology-Microbiology and Health (LR17ES06), Faculty of Sciences, University of Sfax, 3038 Sfax, Tunisia.
Pathol Res Pract. 2023 May;245:154484. doi: 10.1016/j.prp.2023.154484. Epub 2023 Apr 25.
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.
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.
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).
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.
病毒感染在肿瘤发病机制中的作用目前引起了关注。爱泼斯坦-巴尔病毒是一种与多种人类恶性肿瘤相关的病原体，包括乳腺癌。尽管如此，它们在乳腺癌肿瘤中的预后影响很少被研究。因此，我们在研究中试图评估 EBV 在突尼斯乳腺癌中的流行率，并研究其与临床病理特征和总生存的潜在关联。
我们的回顾性研究包括 100 例来自突尼斯乳腺癌的福尔马林固定石蜡包埋样本。通过免疫组织化学分析，使用针对潜伏膜蛋白 1 (LMP-1)的单克隆抗体评估 EBV 感染，并用聚合酶链反应 (PCR) 进行。PCR 阳性标本的一部分进行原位杂交以检测 EBER 表达。使用免疫组织化学方法评估生物标志物的表达。还探索了统计学分析。
ER、PR 和 HER2 的表达状态分别为 81%、71.4%和 33.7%。三重阴性谱在 10.84%的病例中存在。所有乳腺癌标本的 LMP-1 表达均为阴性。PCR 检测显示 44%的患者 EBV 基因组呈阳性。15 例 PCR 阳性病例中均未通过 ISH 显示 EBV 呈阳性结果。根据分子表型，在包括 TN (67%)、Lum B (64%)、HER2+ (50%)和 Lum A (30%)在内的乳腺癌亚组中， EBV DNA 流行率存在统计学差异。双变量分析显示 EBV DNA 与 HER2+显著相关 (p=0.035)、肿瘤大小 (p=0.018) 和高 SBR 分级 (p=0.009)。多因素逻辑回归分析证实 EBV 与肿瘤大小呈正相关 (p=0.048) 和 SBR 分级呈正相关 (p=0.042)。Kaplan-Meier 分析显示 EBV+患者的总生存时间明显短于 EBV-患者 (p=0.032)。
我们的研究表明 EBV DNA 存在于突尼斯乳腺癌中。EBV DNA 与侵袭性特征和总体生存不良相关。需要在更大的样本量中进行进一步研究，以阐明 EBV 在乳腺癌肿瘤进展中的潜在作用。
