Expression of Bak and Bak/Mcl‐1 ratio can predict photodynamic therapy outcome for oral verrucous hyperplasia and leukoplakia

Abstract

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.