Loljung Lotta, Coates Philip J, Nekulova Marta, Laurell Göran, Wahlgren Magnus, Wilms Torben, Widlöf Mikael, Hansel Anna, Nylander Karin
Department of Medical Biosciences/Pathology, Umeå University, Umeå, Sweden.
J Oral Pathol Med. 2014 Jan;43(1):14-9. doi: 10.1111/jop.12074. Epub 2013 Apr 23.
p63 proteins are important in formation of the oral mucosa. Normal oral mucosa shows a balance between the six protein isoforms, whereas an imbalance between them is seen in squamous cell carcinomas (SCC). There is controversy over the clinical impact of p63 in SCC, which may relate to different expression in different areas. In addition, p63 isoforms can act as p53-like molecules (TAp63) or can inhibit p53 functions (ΔNp63) and expression of these isoforms varies in different tumours. Here, we chose to concentrate on the most common intra-oral sub-site, SCC of the mobile tongue.
Total p63, ΔNp63 and TAp63 were analysed separately using immunohistochemistry. The percentage of cells and intensity of expression of different isoforms of p63 was evaluated using a quick score method and correlated with clinical data in a group of 87 patients with tongue SCC.
All tumours expressed p63 in at least 60% of the cells when using two different antibodies detecting all 6 isoforms. p63 expression correlated significantly with 2-year survival (P = 0.018), with fewer patients surviving 2 years if their tumours expressed p63 with strong intensity in at least 80% of the cells (quick score 18). Looking at 5-year survival, this was even more emphasized. ΔNp63 was expressed in all tumours, whereas expression of TAp63 was seen only in 59/87 patients, usually at very low levels.
Based on the present data, we recommend using expression of p63 as an additional factor contributing prognostic information in analysis of SCC in the tongue.
p63蛋白在口腔黏膜形成过程中起着重要作用。正常口腔黏膜中六种蛋白亚型之间保持平衡,而在鳞状细胞癌(SCC)中则出现失衡。p63在SCC中的临床影响存在争议,这可能与不同区域的不同表达有关。此外,p63亚型可作为类似p53的分子(TAp63),也可抑制p53功能(ΔNp63),且这些亚型的表达在不同肿瘤中有所不同。在此,我们选择聚焦于口腔内最常见的亚部位——活动期舌部的SCC。
采用免疫组织化学方法分别分析总p63、ΔNp63和TAp63。使用快速评分法评估p63不同亚型的细胞百分比和表达强度,并将其与87例舌SCC患者的临床数据相关联。
当使用两种检测所有6种亚型的不同抗体时,所有肿瘤中至少60%的细胞表达p63。p63表达与2年生存率显著相关(P = 0.018),如果肿瘤中至少80%的细胞以高强度表达p63(快速评分18),则存活2年的患者较少。观察5年生存率时,这种情况更加明显。所有肿瘤均表达ΔNp63,而仅在59/87例患者中观察到TAp63表达,且通常水平很低。
基于目前的数据,我们建议在分析舌部SCC时,将p63的表达作为提供预后信息的一个额外因素。