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基于人乳头瘤病毒状态的口咽鳞状细胞癌中细胞周期相关蛋白的表达。

Expression of cell cycle-related proteins in oropharyngeal squamous cell carcinoma based on human papilloma virus status.

机构信息

Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, Morioka, Iwate 020-8505, Japan.

Department of Head and Neck Surgery, Miyagi Cancer Center, Natori, Miyagi 981-1293, Japan.

出版信息

Oncol Rep. 2017 Aug;38(2):908-916. doi: 10.3892/or.2017.5720. Epub 2017 Jun 14.

Abstract

The molecular association between human papilloma virus (HPV) and cell cycle-related (CCR) proteins is not fully understood in oropharyngeal squamous cell carcinoma (OPSCC). Herein, we examined the expression levels of CCRs in OPSCCs based on HPV status. In situ hybridization (ISH)- and polymerase chain reaction (PCR)-based assays were used to detect HPV status in 98 OPSCCs, and CCRs were detected by immunostaining. Of 98 tumors, 47 had HPV-positive tumors by either ISH- or PCR-based assays. Concordance analysis between ISH- and PCR-based tests showed a good agreement in OPSCC. Expression of p16 was moderate, consistent with HPV positivity as determined by ISH-based analysis. High p53-, phospho (p)-Rb-, SKP2-, cyclin D1-, and p-c-myc-positive rates were correlated with HPV-negative tumors, whereas high p16- and p27-positive rates were associated with HPV-positive tumors. The positive rates for p21 and cyclin A did not differ between HPV-positive and HPV-negative tumors. Finally, Ki-67 positivity was commonly observed for both types of OPSCCs. Although expression of p16 is thought to be a marker of HPV infection, ISH- or PCR-based tests should be used for HPV detection. In addition, our results regarding CCRs may be helpful for understanding the carcinogenesis of OPSCC.

摘要

人乳头瘤病毒(HPV)与细胞周期相关(CCR)蛋白之间的分子关联在口咽鳞状细胞癌(OPSCC)中尚未完全阐明。在此,我们根据 HPV 状态检查了 OPSCC 中 CCR 的表达水平。使用原位杂交(ISH)和聚合酶链反应(PCR)检测 98 例 OPSCC 中的 HPV 状态,并通过免疫染色检测 CCRs。在 98 个肿瘤中,47 个肿瘤通过 ISH 或基于 PCR 的检测呈 HPV 阳性。ISH 和基于 PCR 的检测之间的一致性分析表明,OPSCC 中存在良好的一致性。p16 的表达为中等水平,与基于 ISH 分析确定的 HPV 阳性一致。高 p53、磷酸化(p)Rb、SKP2、细胞周期蛋白 D1 和 p-c-myc 阳性率与 HPV 阴性肿瘤相关,而高 p16 和 p27 阳性率与 HPV 阳性肿瘤相关。p21 和细胞周期蛋白 A 的阳性率在 HPV 阳性和 HPV 阴性肿瘤之间没有差异。最后,两种类型的 OPSCC 中 Ki-67 阳性均常见。尽管 p16 的表达被认为是 HPV 感染的标志物,但应使用 ISH 或基于 PCR 的检测来检测 HPV。此外,我们关于 CCR 的结果可能有助于理解 OPSCC 的发生机制。

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