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原发性乳腺癌及前哨淋巴结转移中人类巨细胞病毒蛋白和核酸的高流行率。

High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes.

机构信息

Department of Medicine, Karolinska University Hospital, Stockholm, Sweden.

出版信息

PLoS One. 2013;8(2):e56795. doi: 10.1371/journal.pone.0056795. Epub 2013 Feb 22.

Abstract

BACKGROUND

Breast cancer is a leading cause of death among women worldwide. Increasing evidence implies that human cytomegalovirus (HCMV) infection is associated with several malignancies. We aimed to examine whether HCMV is present in breast cancer and sentinel lymph node (SLN) metastases.

MATERIALS AND METHODS

Formalin-fixed paraffin-embedded tissue specimens from breast cancer and paired sentinel lymph node (SLN) samples were obtained from patients with (n = 35) and without SLN metastasis (n = 38). HCMV immediate early (IE) and late (LA) proteins were detected using a sensitive immunohistochemistry (IHC) technique and HCMV DNA by real-time PCR.

RESULTS

HCMV IE and LA proteins were abundantly expressed in 100% of breast cancer specimens. In SLN specimens, 94% of samples with metastases (n = 34) were positive for HCMV IE and LA proteins, mostly confined to neoplastic cells while some inflammatory cells were HCMV positive in 60% of lymph nodes without metastases (n = 35). The presence of HCMV DNA was confirmed in 12/12 (100%) of breast cancer and 10/11 (91%) SLN specimens from the metastatic group, but was not detected in 5/5 HCMV-negative, SLN-negative specimens. There was no statistically significant association between HCMV infection grades and progesterone receptor, estrogen receptor alpha and Elston grade status.

CONCLUSIONS

The role of HCMV in the pathogenesis of breast cancer is unclear. As HCMV proteins were mainly confined to neoplastic cells in primary breast cancer and SLN samples, our observations raise the question whether HCMV contributes to the tumorigenesis of breast cancer and its metastases.

摘要

背景

乳腺癌是全球女性死亡的主要原因。越来越多的证据表明,人类巨细胞病毒(HCMV)感染与多种恶性肿瘤有关。我们旨在研究 HCMV 是否存在于乳腺癌和前哨淋巴结(SLN)转移中。

材料和方法

从患有(n=35)和不伴有 SLN 转移的(n=38)患者的乳腺癌和配对 SLN 样本中获得福尔马林固定石蜡包埋组织标本。使用敏感的免疫组织化学(IHC)技术检测 HCMV 早期(IE)和晚期(LA)蛋白,并通过实时 PCR 检测 HCMV DNA。

结果

HCMV IE 和 LA 蛋白在 100%的乳腺癌标本中大量表达。在 SLN 标本中,94%(n=34)有转移的样本中 HCMV IE 和 LA 蛋白阳性,大多数局限于肿瘤细胞,而在 60%(n=35)无转移的淋巴结中,一些炎症细胞呈 HCMV 阳性。在转移性组的 12/12(100%)乳腺癌和 10/11(91%)SLN 标本中均证实存在 HCMV DNA,但在 5/5 HCMV 阴性、SLN 阴性标本中未检测到。HCMV 感染程度与孕激素受体、雌激素受体 alpha 和 Elston 分级状态之间没有统计学显著关联。

结论

HCMV 在乳腺癌发病机制中的作用尚不清楚。由于 HCMV 蛋白主要局限于原发性乳腺癌和 SLN 样本中的肿瘤细胞,我们的观察结果提出了一个问题,即 HCMV 是否有助于乳腺癌及其转移的肿瘤发生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9449/3579924/e4d55c803fdb/pone.0056795.g001.jpg

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