一种预测口腔鳞状细胞癌预后的免疫组织化学评分。

An immunohistochemical score to predict the outcome for oral squamous cell carcinoma.

机构信息

Medicine and Oral Surgery Department, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), University Institute of Health Sciences (IUCS), CESPU, Paredes, Portugal.

Medical-Surgical Dentistry Research Group (OMEQUI), Health Research Institute of Santiago de Compostela (IDIS), University of Santiago de Compostela, Santiago de Compostela, Spain.

出版信息

J Oral Pathol Med. 2018 Apr;47(4):375-381. doi: 10.1111/jop.12682. Epub 2018 Feb 10.

DOI:10.1111/jop.12682

PMID:29344992

Abstract

BACKGROUND

Oral cancer is a major public health problem worldwide, with a poor survival. Our aim was to evaluate several protein markers in oral squamous cell carcinomas (OSCC) and analyse their prognostic value on patient's survival.

METHODS

We analysed the expression of EGFR, p53, p27, p16, cyclin D1, cyclin A2, COX-2, Ki-67, Bcl-2, VEGFR-1 and VEGFR-2, by immunohistochemistry on 67 primary OSCC. Cancer-specific survival (CSS) analysis was evaluated by the Cox regression model.

RESULTS

Markers showed variable expression between 27.9% and 95.2%. In univariate analysis for CSS, we found that four of the tested markers, namely high expression of p53 (P = .001), EGFR (P = .003), cyclin A2 (P = .005) and low expression of p16 (P = .019), along with clinical stage (P < .001), tumour size (P < .001), presence of nodal metastasis (P < .001) and perineural permeation (P = .039) were related to decreased survival. On the basis of these results, we constructed an immunohistochemical score hinging on the possibility that any tumour could express none of these four markers (score 0), one or two markers (score 1) and three or more markers (score 2). In multivariable analysis, this immunohistochemical score revealed an independent prognostic value on cancer-specific survival (P = .001; HR: 3.7: 95%CI 1.7-7.9). Moreover, we confirmed that in early-stage tumours (stage I or II) this score maintained its independent prognostic value (P = .025; HR: 7.9, 95%CI 1.3-49.1) on CSS.

CONCLUSION

The expression of the markers p53, p16, EGFR and cyclin A in OSCC, combined to give an immunohistochemical score, may identify high-risk subgroups for decreased survival and to further guide therapeutic decisions.

摘要

背景

口腔癌是全球主要的公共卫生问题之一，其生存率较差。我们的目的是评估口腔鳞状细胞癌（OSCC）中的几种蛋白标志物，并分析其对患者生存的预后价值。

方法

我们通过免疫组织化学方法分析了 67 例原发性 OSCC 中 EGFR、p53、p27、p16、cyclin D1、cyclin A2、COX-2、Ki-67、Bcl-2、VEGFR-1 和 VEGFR-2 的表达。通过 Cox 回归模型评估癌症特异性生存（CSS）分析。

结果

标志物的表达在 27.9%到 95.2%之间变化。在 CSS 的单因素分析中，我们发现四个测试标志物中的四个标志物，即 p53 高表达（P =.001）、EGFR 高表达（P =.003）、cyclin A2 高表达（P =.005）和 p16 低表达（P =.019），以及临床分期（P <.001）、肿瘤大小（P <.001）、淋巴结转移（P <.001）和神经周围渗透（P =.039）与生存降低有关。基于这些结果，我们构建了一个免疫组织化学评分，其基础是任何肿瘤都有可能不表达这四个标志物中的任何一个（评分 0）、一个或两个标志物（评分 1）和三个或更多标志物（评分 2）。在多变量分析中，该免疫组织化学评分对癌症特异性生存具有独立的预后价值（P =.001；HR：3.7：95%CI 1.7-7.9）。此外，我们证实，在早期肿瘤（I 期或 II 期）中，该评分在 CSS 上仍然具有独立的预后价值（P =.025；HR：7.9，95%CI 1.3-49.1）。