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通过靶向EBERs和病毒基因组的原位杂交检测宫颈癌中的爱泼斯坦-巴尔病毒(EBV)

Epstein-barr virus (EBV) in cervical carcinoma detected by in situ hybridization targeting ebers and the viral genome.

作者信息

Silva Álife Diêgo Lima, Marelli Julia Graziele Alves, Lira Lopes Maria Willaiara, Rodrigues Myrella Tavares, Lopes Cecília Paz, Silva José Nairton Coelho, Machado Sávio Samuel Feitosa, da Silva Souza Racquel Oliveira, Tibúrcio Maria Aparecida, Sampaio Alexandre Quental, Fernandes Isabelle Joyce de Lima Silva, do Ó Pessoa Claudia, da Silva Cláudio Gleidiston Lima, de Lima Marcos Antonio Pereira

机构信息

Laboratory of Microbiology, Immunology and Parasitology (LAMIP), Faculty of Medicine, Federal University of Cariri, Barbalha, Ceará, Brazil.

Experimental Pathology Laboratory (LAPEX), Faculty of Medicine, Federal University of Cariri, Barbalha, Ceará, Brazil.

出版信息

Braz J Microbiol. 2025 Sep 16. doi: 10.1007/s42770-025-01774-y.

Abstract

Epstein-Barr virus (EBV) infection has been suggested as a potential cofactor for the development and progression of cervical cancer, collaborating with high-risk Human Papillomavirus (HR-HPV). In situ hybridization (ISH) has been considered the gold standard in the investigation of EBV in neoplasms. This study aimed to detect EBV in cervical carcinoma samples using ISH targeting EBERs (EBER-ISH) and the BamHI-W region of the viral genome (BamHI-W-ISH), and compare the results of both targets. Of the 88 cases collected, 9 were EBER-ISH positive (10.2%), while 33 (37.5%) cases were positive for EBV by BamHI-W-ISH, all showing staining in the nuclei of the malignant cells. No statistically significant results were found between the presence of EBV and carcinoma type, differentiation grade or tumor staging. The kappa agreement index between the two targets was 0.092. Only 4 cases were EBER-ISH(+) and BamHI-W-ISH(-). On the other hand, 28 cases were BamHI-W-ISH(+) and EBER-ISH(-). Altogether, 37/88 (42%) cases were EBV-positive by one or both targets. Infected lymphocytes were verified in 9 (10.2%) and 34 (38.6%) cases, by EBER-ISH and BamHI-W-ISH, respectively. The slight agreement demonstrated between the targets may be due to the lack of expression of EBERs, suggesting that EBV may present a distinct latency pattern in the cervical mucosa, or that it has entered the replicative cycle in some of these tumors, in both cases, explaining the low positivity rate verified through EBER-ISH, while calling into question the latter's gold standard status in the detection of EBV in malignancies. Our findings also indicate that the chosen viral genomic target may represent a suitable candidate for EBV detection by ISH.

摘要

爱泼斯坦-巴尔病毒(EBV)感染被认为是宫颈癌发生和发展的潜在辅助因素,与高危人乳头瘤病毒(HR-HPV)协同作用。原位杂交(ISH)被认为是肿瘤中EBV检测的金标准。本研究旨在使用靶向EBERs的ISH(EBER-ISH)和病毒基因组的BamHI-W区域(BamHI-W-ISH)检测宫颈癌样本中的EBV,并比较两个靶点的结果。在收集的88例病例中,9例EBER-ISH阳性(10.2%),而33例(37.5%)病例通过BamHI-W-ISH检测EBV呈阳性,所有病例均显示恶性细胞核染色。EBV的存在与癌型、分化程度或肿瘤分期之间未发现统计学显著结果。两个靶点之间的kappa一致性指数为0.092。仅4例为EBER-ISH(+)且BamHI-W-ISH(-)。另一方面,28例为BamHI-W-ISH(+)且EBER-ISH(-)。总之,88例中有37例(42%)通过一个或两个靶点检测EBV呈阳性。分别通过EBER-ISH和BamHI-W-ISH在9例(10.2%)和34例(38.6%)病例中验证了感染的淋巴细胞。两个靶点之间显示的轻微一致性可能是由于EBERs缺乏表达,这表明EBV在宫颈黏膜中可能呈现不同的潜伏模式,或者它在其中一些肿瘤中进入了复制周期,在这两种情况下,都解释了通过EBER-ISH验证的低阳性率,同时质疑了后者在恶性肿瘤中EBV检测的金标准地位。我们的研究结果还表明,所选的病毒基因组靶点可能是ISH检测EBV的合适候选者。

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