p63 过表达与口腔鳞状细胞癌的辐射抗性和预后相关。

Overexpression of p63 is associated with radiation resistance and prognosis in oral squamous cell carcinoma.

机构信息

Department of Oral and Maxillofacial Surgery, University of Mainz, Medical Center, Mainz, Germany.

出版信息

Oral Oncol. 2010 Sep;46(9):667-71. doi: 10.1016/j.oraloncology.2010.06.012. Epub 2010 Jul 24.

DOI:10.1016/j.oraloncology.2010.06.012

PMID:20656547

Abstract

BACKGROUND

The tumor suppressor homologue p63 is expressed in basal and parabasal layers of intraoral mucosa. Full length transcripts with transactivational domain (TA forms) present with homology to p53 and implicate functions governing cell proliferation, differentiation and apoptosis control. To date studies show an increase of p63 expression in oral dysplasia and additionally high expression levels correlated with poor prognosis for patients with OSCC, whereas a possible link to radiation resistance of tumors has not been investigated yet. In the present study we tested the hypothesis for p63 being a marker of radioresistance and overall survival in OSCC.

METHODS

p63 Expression was labeled by immunohistochemistry in pre-treatment biopsies collected from 33 patients with OSCC. Quantification of the labeling index (Li) based on the relation of p63 positive cells to overall tumor cell count. Histological examination of the resection specimen allowed categorization of the radiation response. Statistical analyses of the association between Li and radiation response were performed. Survival analysis utilized Kaplan-Meier estimates and additionally a Cox regression model was built for p63 (Li), T stage, N-stage and chemotherapy and presented as hazard ratios.

RESULTS

All tumors had enhanced p63 expression. The median Li was 63.1% (range 36-87%). Tumors with a p63 positive cell count>63.1% showed increased resistance to radiation (p=0.027). Overall survival was higher (p=0.001) for patients with low Li (<median value) than those with high Li (>median value) and multivariate Cox regression analysis confirmed the significance of p63 as a prognostic marker of survival.

CONCLUSIONS

The results of this analysis advocate p63 expression in pre-treatment tumor tissue to be a marker of radiation resistance in OSCC, with high expression levels being associated with poor radiation response and shorter survival. The promising results of this biomarker should now be confirmed by a study with larger patient counts.

摘要

背景

肿瘤抑制同源物 p63 在口腔黏膜的基底层和副基底层表达。具有转录激活域（TA 形式）的全长转录本与 p53 具有同源性，并暗示了控制细胞增殖、分化和凋亡控制的功能。迄今为止的研究表明，p63 在口腔发育不良中的表达增加，此外，高表达水平与 OSCC 患者的预后不良相关，而 p63 与肿瘤的放射抵抗之间可能存在联系尚未得到研究。在本研究中，我们检验了 p63 作为 OSCC 放射抵抗和总生存的标志物的假设。

方法

在 33 名 OSCC 患者的治疗前活检中，通过免疫组织化学标记 p63 表达。根据 p63 阳性细胞与总肿瘤细胞计数的关系，对标记指数（Li）进行量化。切除标本的组织学检查允许对放射反应进行分类。对 Li 与放射反应之间的关联进行了统计学分析。生存分析利用 Kaplan-Meier 估计值，并且还为 p63（Li）、T 分期、N 分期和化疗构建了 Cox 回归模型，并以危险比表示。

结果

所有肿瘤均增强了 p63 表达。Li 的中位数为 63.1%（范围 36-87%）。p63 阳性细胞计数>63.1%的肿瘤对放射的抵抗力增加（p=0.027）。Li<中位数（<中位数）的患者的总生存率高于 Li>中位数（>中位数）的患者（p=0.001），多变量 Cox 回归分析证实了 p63 作为生存预后标志物的意义。