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HPV-related Sinonasal Carcinoma: Clinicopathologic Features, Diagnostic Utility of p16 and Rb Immunohistochemistry, and EGFR Copy Number Alteration.
HPV 相关鼻窦癌: 临床病理特征、 p16 和 Rb 免疫组织化学的诊断效用以及 EGFR 拷贝数改变。

摘要

The prevalence and prognostic value of human papillomavirus (HPV) infection and epidermal growth factor receptor (EGFR) alteration in sinonasal squamous cell carcinoma (SNSCC) are not known. The reliability of p16 overexpression as a surrogate for HPV infection in SNSCC is also unclear. We investigated the prognostic and diagnostic significances of HPV infection, EGFR alteration, and p16 expression in SNSCC. We analyzed high-risk HPV infection by HPV-RNA in situ hybridization and EGFR gene copy number gain (CNG) by chromogenic in situ hybridization and by determining the protein expressions of p16, Rb, and EGFR by immunohistochemistry in 101 SNSCC cases. HPV infection (n=9, 8.9%) and p16 overexpression (n=15, 14.9%) were associated with better overall survival (P=0.0042 and 0.005, respectively). The HPV cases were located predominantly at the nasal cavity with nonkeratinizing histology and partial loss of Rb. Notably, 40% (6/15) of p16 SNSCCs were HPV. Two of these cases showed complete loss of Rb expression by immunohistochemistry, suggesting a reason for the above discrepancy. EGFR CNG, detected in 30.5% of the SNSCCs, was correlated with EGFR protein overexpression (P=0.0001). HPV infection and EGFR CNG were mutually exclusive. The HPV/EGFR CNG group had significantly better overall survival than the HPV/EGFR CNG and HPV/EGFR CNG groups (P=0.0471 and 0.0343, respectively). Our results suggest that HPV infection is a favorable prognostic marker in SNSCC, but p16 is not a perfect surrogate marker; the Rb expression pattern may improve the diagnostic accuracy. The molecular subclassification of SNSCCs based on HPV infection and EGFR copy number status might provide important information for therapeutic strategies.

译文

人乳头瘤病毒 (HPV) 感染和表皮生长因子受体 (EGFR) 改变在鼻腔鼻窦鳞状细胞癌 (SNSCC) 中的患病率和预后价值尚不清楚。P16 过表达作为 SNSCC 中 HPV 感染替代品的可靠性也不清楚。我们研究了 SNSCC 中 HPV 感染、 EGFR 改变和 p16 表达的预后和诊断意义。我们通过 HPV-RNA 原位杂交分析了高危型 HPV 感染,通过显色原位杂交分析了 EGFR 基因拷贝数增加 (CNG),并通过测定 p16 、 Rb 、 101 例 SNSCC 病例的免疫组织化学和 EGFR。人乳头状瘤病毒感染 (n = 8.9%) 和 p16 过表达 (n = 14.9%) 与更好的总生存期相关 (分别为 P = 0.0042 和 0.005)。HPV 病例主要位于鼻腔,组织学上无角化,部分 Rb 缺失。值得注意的是,40% (6/15) 的 p16 SNSCCs 是人乳头状瘤病毒。其中两例通过免疫组织化学显示 Rb 表达完全缺失,这表明了上述差异的原因。在 30.5% 的 SNSCCs 中检测到的 EGFR CNG 与 EGFR 蛋白过表达相关 (P = 0.0001)。HPV 感染和 EGFR CNG 是相互排斥的。人乳头状瘤病毒/表皮生长因子受体 CNG 组的总生存期明显优于人乳头状瘤病毒/表皮生长因子受体 CNG 组和人乳头状瘤病毒/表皮生长因子受体 CNG 组 (分别为 P = 0.0471 和 0.0343)。我们的结果表明,人乳头状瘤病毒感染是 SNSCC 的有利预后标记,但 p16 不是完美的替代标记; Rb 表达模式可能提高诊断准确性。基于 HPV 感染和 EGFR 拷贝数状态的 SNSCCs 分子分型可能为治疗策略提供重要信息。

Immunohistochemistry

肿瘤 病理诊断 实验技术
概述  :  

免疫组织化学又简称为免疫组化,是应用免疫学基本原理——抗原抗体反应,即抗原与抗体特异性结合的原理,通过化学反应使标记抗体的显色剂(荧光素、酶、金属离子或是同位素)显色,利用光学显微镜、荧光显微镜或电子显微镜进行实验结果观察,从而确定组织细胞内抗原(多肽或者蛋白质),对其进行定位、定性以及定量的研究,称之为免疫组织化学技术,又可称为免疫细胞化学(ICC,immunocytochemistry)。该技术是病理诊断中常规的技术手段。 原理 IHC技术的基本原理是利用了抗体和抗原之间的高

Immunohistochemistry   /'ɪmjʊnəʊ,hɪstəʊ'kemɪstrɪ/ 

       免疫组织化学

同根词   immunological   adj. 免疫学的

       The RPE cells were identified by DOPA staining and immunohistochemistry.

               用多巴(DOPA)染色和免疫组织化学鉴定RPE细胞。

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