Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis.
Inflammatory breast cancer: high incidence of detection of mixed human cytomegalovirus genotypes associated with disease pathogenesis.
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DOI：
10.3389/fonc.2014.00246
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发表时间：
2014
影响因子：
4.7
通讯作者：
Mohamed MM
中科院分区：
文献类型：
--
作者：
Mohamed HT;El-Shinawi M;Nouh MA;Bashtar AR;Elsayed ET;Schneider RJ;Mohamed MM
炎症性乳腺癌（IBC）是一种高度转移性、侵袭性和致命性的乳腺癌。表现为IBC的患者的特征在于大量腋窝淋巴结转移。最近，我们发现，IBC癌组织含有显着更高水平的人巨细胞病毒（HCMV）DNA相比，其他乳腺癌组织，可能会调节细胞信号通路。事实上，HCMV发病机制和临床结果与IBC中的多种HCMV基因型在统计学上相关。因此，在本研究中，我们建立了感染的非IBC与IBC患者癌组织中HCMV基因型的发生率和类型。我们还评估了HCMV混合基因型检测与疾病进展之间的相关性。HCMV基因分型结果显示，非IBC组和IBC组HCMV基因型均以糖蛋白B（gB）-1和糖蛋白N（gN）-1为主，两组间差异无统计学意义。然而，与非IBC患者相比，IBC癌组织中gN-3b基因型的检测发生率在统计学上显著更高。gB混合基因型的检出率在IBC患者中显示gB-1 + gB-3的检出率显著高于非IBC患者。同样，gN混合基因型的检出率显示，gN-1 + gN-3b和gN-3 + gN-4 b/c在IBC癌组织中的检出率显著高于非IBC癌组织。不同HCMV基因型的混合存在被发现与非IBC中的转移淋巴结数量显著相关，但在IBC患者中不相关。在IBC患者中，混合HCMV不同基因型的检测与淋巴管浸润和真皮淋巴栓的形成显著相关，而在非IBC患者中未发现。
Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer. Patients presenting with IBC are characterized by a high number of axillary lymph node metastases. Recently, we found that IBC carcinoma tissues contain significantly higher levels of human cytomegalovirus (HCMV) DNA compared to other breast cancer tissues that may regulate cell signaling pathways. In fact, HCMV pathogenesis and clinical outcome can be statistically associated with multiple HCMV genotypes within IBC. Thus, in the present study, we established the incidence and types of HCMV genotypes present in carcinoma tissues of infected non-IBC versus IBC patients. We also assessed the correlation between detection of mixed genotypes of HCMV and disease progression. Genotyping of HCMV in carcinoma tissues revealed that glycoprotein B (gB)-1 and glycoprotein N (gN)-1 were the most prevalent HCMV genotypes in both non-IBC and IBC patients with no significant difference between patients groups. IBC carcinoma tissues, however, showed statistically significant higher incidence of detection of the gN-3b genotype compared to non-IBC patients. The incidence of detection of mixed genotypes of gB showed that gB-1 + gB-3 was statistically significantly higher in IBC than non-IBC patients. Similarly, the incidence of detection of mixed genotypes of gN showed that gN-1 + gN-3b and gN-3 + gN-4b/c were statistically significant higher in the carcinoma tissues of IBC than non-IBC. Mixed presence of different HCMV genotypes was found to be significantly correlated with the number of metastatic lymph nodes in non-IBC but not in IBC patients. In IBC, detection of mixed HCMV different genotypes significantly correlates with lymphovascular invasion and formation of dermal lymphatic emboli, which was not found in non-IBC patients.