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高危型人乳头瘤病毒通过激活PI3K/Akt、pRb和TERT信号通路,增强人乳头瘤病毒相关多表型鼻窦癌中COX-2、VEGF、EGFR、ProEx-C和TERT蛋白的表达。

High-risk human papillomavirus enhances the expression of COX-2 VEGF, EGFR, ProEx-C, and TERT proteins in human papillomavirus-related multiphenotypic sinonasal carcinoma through activation of PI3K/Akt, pRb, and TERT signalling pathways.

作者信息

Hanafy Sabah, Elhasadi Ibtesami, Alabiad Mohamed, Refaat Mohamed, Bakry Adel, Abdulmageed Alsayed, Shalaby Amany, Jaber Fatima A, Gobran Mai Ahmed

机构信息

Department of Pathology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Department of Pathology, Faculty of Medicine, University of Benghazi, Benghazi, Libya.

出版信息

Pol J Pathol. 2022;73(4):283-298. doi: 10.5114/pjp.2022.125819.

Abstract

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a new type of sinonasal tumour that frequently drops out of accurate diagnosis. Human papillomavirus related multiphenotypic sinonasal carcinoma was previously known as HPV-related sinonasal carcinoma with adenoid cystic characteristics, and it is connected to high-risk HPV (HR-HPV) strains whose prognosis is unknown. We aim to evaluate PI3K/Akt, pRb, and h telomerase reverse transcriptase (TERT) signalling pathway activation through the expression of proteins cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), ProEx-C, and TERT and their prognostic and clinicopathological value in HMSC patients. Sections of the 40 paraffin blocks of HMSC were recovered, and all samples were evaluated for the presence of a cocktail of HR-HPV, and the absence of MYB, NFIB, and MYBL1 fusions using fluorescence in situ hybridization; the presence of myoepithelial markers; S100, actin; the presence of squamous differentiation markers; calponin, p40, and p63 using PCR-based assays; and COX-2,VEGF, ProEx-C, and TERT using immunohistochemical staining. All patients were monitored for around 54 months, until death, or the last known surviving data (range 20-60 months). A statistically significant relationship exists between COX-2 expression was significantly related to the old age group, tumour extent, relapse, mortality, and poor DFS; (p = 0.001), (p = 0.01), (p = 0.002), and (p = 0.035), respectively. While VEGF, ProEx-C, and TERT expression with the old age group, tumour extent, lymph node metastasis, advancedstaging, relapse, mortality, poor disease free survival (DFS), and overall survival (p = 0.001). Human papillomavirus-related multiphenotypic sinonasal carcinoma is a unique sinonasal neoplasm with a strong link to HR-HPV strains. Expression of COX-2, VEGF, EGFR, ProEx-C, TERT was linked to poor prognosis, survival, and aggressive malignant behaviours such as proliferation, local recurrence, and lymph node metastasis, making them novel beneficial biomarkers and targeted therapies for HMSC patients.

摘要

人乳头瘤病毒(HPV)相关的多表型鼻窦癌(HMSC)是一种新型鼻窦肿瘤,常常难以得到准确诊断。人乳头瘤病毒相关的多表型鼻窦癌以前被称为具有腺样囊性特征的HPV相关鼻窦癌,它与高危HPV(HR-HPV)毒株有关,其预后尚不清楚。我们旨在通过环氧化酶-2(COX-2)、血管内皮生长因子(VEGF)、ProEx-C和端粒酶逆转录酶(TERT)蛋白的表达来评估PI3K/Akt、pRb和h端粒酶逆转录酶信号通路的激活情况,以及它们在HMSC患者中的预后和临床病理价值。回收了40个HMSC石蜡块切片,所有样本均通过荧光原位杂交评估HR-HPV混合物的存在情况以及MYB、NFIB和MYBL1融合的缺失情况;通过基于PCR的检测评估肌上皮标志物S100、肌动蛋白的存在情况;通过基于PCR的检测评估鳞状分化标志物钙调蛋白、p40和p63的存在情况;通过免疫组织化学染色评估COX-2、VEGF、ProEx-C和TERT。对所有患者进行了约54个月的监测,直至死亡或最后已知的存活数据(范围为20 - 60个月)。COX-2表达与老年组、肿瘤范围、复发、死亡率和无病生存期差之间存在统计学显著关系;(p = 0.001)、(p = 0.01)、(p = 0.002)和(p = 0.035),分别。而VEGF、ProEx-C和TERT表达与老年组、肿瘤范围、淋巴结转移、晚期分期、复发、死亡率、疾病无进展生存期(DFS)差和总生存期之间存在统计学显著关系(p = 0.001)。人乳头瘤病毒相关的多表型鼻窦癌是一种独特的鼻窦肿瘤,与HR-HPV毒株有很强的联系。COX-2、VEGF、表皮生长因子受体(EGFR)、ProEx-C、TERT的表达与预后不良、生存期短以及增殖、局部复发和淋巴结转移等侵袭性恶性行为有关,使其成为HMSC患者新的有益生物标志物和靶向治疗方法。

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