Santoro Angela, Angelico Giuseppe, Arciuolo Damiano, Scaglione Giulia, Padial Urtueta Belen, Aquino Gabriella, Starita Noemy, Tornesello Maria Lina, Rega Rosalia Anna, Pedicillo Maria Carmela, Mazzucchelli Manuel, Stefano Ilenia Sara De, Zamparese Rosanna, Campisi Giuseppina, Mori Giorgio, Zannoni Gian Franco, Pannone Giuseppe
General Pathology Unit, Department of Woman and Child's Health and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy.
Istituto di Anatomia Patologica, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy.
Curr Issues Mol Biol. 2024 Oct 10;46(10):11282-11295. doi: 10.3390/cimb46100670.
Growing scientific evidence suggests a link between the expression of toll-like receptor 4 (TLR4) and cervical cancer carcinogenesis. Specifically, a close relation between TLR4 expression and FIGO stage, lymph node metastases, and tumor size has been reported in cervical cancer. In the present study, we aimed to evaluate the relationship between TLR4 expression levels and human papillomavirus (HPV) infection and/or high-risk (hr) HPV integration status in patients with a histological diagnosis of high-grade squamous intraepithelial lesion (H-SIL), and squamous cell carcinoma (SCC) of the uterine cervix. Sixty biopsies of cervical neoplasia, comprising H-SIL (n = 20) and SCC (n = 40), were evaluated for TLR4 expression by immunohistochemistry. All samples were positive for high-risk HPV as confirmed by in situ hybridization (ISH) and broad-spectrum PCR followed by Sanger sequencing analysis. The intensity of TLR4 staining was higher in tissues negative for intraepithelial lesion or malignancy (NILM) than in H-SIL, and further reduced in SCC. Moreover, statistically significant differences have been observed in the percentage of TLR4 expression between NILM and H-SIL and between H-SIL and SCC, with higher percentages of expression in H-SIL than in SCC. Our results showed a significant downregulation of TLR4 in HPV-related H-SIL and SCC, compared to NILM. These data support the hypothesis that TLR4 expression is suppressed in HPV-driven oncogenesis.
越来越多的科学证据表明，Toll样受体4（TLR4）的表达与宫颈癌的发生之间存在联系。具体而言，已有报道称宫颈癌中TLR4表达与国际妇产科联盟（FIGO）分期、淋巴结转移及肿瘤大小密切相关。在本研究中，我们旨在评估组织学诊断为高级别鳞状上皮内病变（H-SIL）和子宫颈鳞状细胞癌（SCC）患者的TLR4表达水平与人类乳头瘤病毒（HPV）感染和/或高危（hr）HPV整合状态之间的关系。通过免疫组织化学对60例宫颈肿瘤活检组织进行评估，其中包括H-SIL（n = 20）和SCC（n = 40），以检测TLR4表达。通过原位杂交（ISH）、广谱聚合酶链反应（PCR）及桑格测序分析证实，所有样本高危HPV均呈阳性。TLR4染色强度在无上皮内病变或恶性肿瘤（NILM）的组织中高于H-SIL，在SCC中进一步降低。此外，在NILM与H-SIL之间以及H-SIL与SCC之间，TLR4表达百分比存在统计学显著差异，H-SIL中的表达百分比高于SCC。我们的结果显示，与NILM相比，HPV相关的H-SIL和SCC中TLR4显著下调。这些数据支持了TLR4表达在HPV驱动的肿瘤发生过程中受到抑制这一假说。
