School of Dentistry, College of Oral Medicine, Chung Shan Medical University, Taichung, Taiwan.
J Oral Pathol Med. 2013 Mar;42(3):257-62. doi: 10.1111/jop.12007. Epub 2012 Sep 14.
Our previous studies showed that topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is very effective for oral verrucous hyperplasia (OVH) and relatively less effective for oral leukoplakia (OL) lesions. Nevertheless, there has been no report on the association of the expression of apoptosis-related proteins in OVH and OL biopsy tissues prior to PDT with PDT treatment outcomes.
This study used immunohistochemistry to evaluate whether the expression of Bak, Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein in biopsy specimens of OVH and OL lesions could be used to predict the clinical outcomes of 18 OVH and 40 OL lesions treated with topical ALA-PDT. The marker labeling score (LS) was defined as labeling index (positive cells/total cells) multiplied by staining intensity. The lesions after ALA-PDT treatment were divided into complete response (CR) group and partial or no response (PR/NR) group.
The mean Bak LS and the mean Bak/Mcl-1 LS ratio were significantly higher in the CR group than in the PR/NR group. However, there was no significant difference in the Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, or PCNA protein LS between the CR and PR/NR groups.
We conclude that the Bak LS or Bak/Mcl-1 LS ratio may be a useful biomarker to predict the clinical outcomes of OVH and OL lesions treated with topical ALA-PDT. Pre-PDT epithelial cell levels of Mcl-1, caspase-3, caspase-8, caspase-9, p53, p21, and PCNA may not have a significant influence on the clinical outcome of OVH and OL lesions treated with topical ALA-PDT.
我们之前的研究表明,局部 5-氨基酮戊酸介导的光动力疗法(ALA-PDT)对口腔疣状增生(OVH)非常有效,而对口腔白斑(OL)病变的效果相对较差。然而,目前还没有关于 OVH 和 OL 活检组织中与 PDT 治疗前凋亡相关蛋白表达与 PDT 治疗结果之间的关联的报道。
本研究采用免疫组织化学方法评估 OVH 和 OL 病变活检标本中 Bak、Mcl-1、caspase-3、caspase-8、caspase-9、p53、p21 或 PCNA 蛋白的表达是否可用于预测 18 例 OVH 和 40 例 OL 病变经局部 ALA-PDT 治疗的临床结局。标记物标记评分(LS)定义为标记指数(阳性细胞/总细胞)乘以染色强度。ALA-PDT 治疗后的病变分为完全缓解(CR)组和部分缓解或无缓解(PR/NR)组。
CR 组的 Bak LS 和 Bak/Mcl-1 LS 比值的平均值明显高于 PR/NR 组。然而,CR 组和 PR/NR 组之间的 Mcl-1、caspase-3、caspase-8、caspase-9、p53、p21 或 PCNA 蛋白 LS 无显著差异。
我们得出结论,Bak LS 或 Bak/Mcl-1 LS 比值可能是预测局部 ALA-PDT 治疗 OVH 和 OL 病变临床结局的有用生物标志物。治疗前上皮细胞中 Mcl-1、caspase-3、caspase-8、caspase-9、p53、p21 和 PCNA 的水平可能对局部 ALA-PDT 治疗 OVH 和 OL 病变的临床结局没有显著影响。