Ki67, CD105, and α-SMA expression supports the transformation relevant dysplastic features in the atrophic epithelium of oral submucous fibrosis

Amol R Gadbail,Satyajit A Tekade,Sachin C Sarode,Prajakta Zade,Shailesh Gondivkar,Gargi S Sarode,Minal Chaudhary,Shankargouda Patil,Alka Hande,Gururaj Arakeri

doi:10.1371/journal.pone.0200171

Abstract

BackgroundThe grading of oral epithelial dysplasia is not possible in the atrophic epithelium of oral submucous fibrosis (OSMF). Recently, we found that features such as increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, increased nuclear size, and hyperchromasia represent transformation-relevant dysplastic features in the atrophic epithelium of OSMF. The presence of these features can be considered a high-risk feature for patients. However, these findings have not been tested and authenticated using markers relevant to oral carcinogenesis.MethodParaffin-embedded tissues from 30 normal oral mucosa (NOM) and 50 OSMF were retrieved from 2008 to 2016 and subjected to immunohistochemical expression using Ki67, CD105 and α-SMA antibodies.ResultsKi67 LI showed significant increases from NOM (12.47±2.34) to LRED (23.47±3.75) to HRED (34.31±7.31) (<0.0001). Similarly, MVD was increased significantly from NOM (3.53±5.17) to LRED (27.57±12.25) to HRED (46.18±12.55) (p<0.0001). The expression of α-SMA was significantly increased from LRED (0.21±0.41) to HRED (1.13±0.56) (<0.0001). The Ki67 LI and α-SMA; MVD and α-SMA; and Ki67Ki67 LI and MVD in NOM, LRED and HRED showed a statistically significant positive correlation (P<0.0001). The increase in Ki67 LI was directly proportional to MVD and α-SMA expression from NOM to LRED to HRED (P<0.0001). The connective tissue stroma of NOM lacks α-SMA expression. Mild myofibroblast expression was noted in 4 cases of LRED (14.28%) and in 18 cases of HRED (81.81%). Moderate expression was noted only in 4 cases of HRED (22.22%).ConclusionKi67 LI, CD105, and α-SMA expression showed significant differences between normal, LRED and HRED. These findings further support that features such as increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, and hyperchromasia could be transformation-relevant dysplastic features.

Highlights

Oral epithelial dysplasia (OED) is currently used as a tool for predicting malignant potential and determining the treatment strategy for oral potentially malignant disorders (OPMDs)
The expression of α-SMA was significantly increased from low-risk epithelial dysplasia (LRED) (0.21±0.41) to highrisk epithelial dysplasia (HRED) (1.13±0.56) (
Ki67 labeling index (LI), CD105, and α-SMA expression showed significant differences between normal, LRED and HRED. These findings further support that features such as increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, and hyperchromasia could be transformation-relevant dysplastic features

Summary

Introduction

Oral epithelial dysplasia (OED) is currently used as a tool for predicting malignant potential and determining the treatment strategy for oral potentially malignant disorders (OPMDs). The criteria for the current grading system of OED, which is based on the thickness (height) of the cellular and architectural changes, will not be applicable for OSMF This finding raises the question about the authenticity of previous studies that have mentioned OED in OSMF. We found that features such as increased basal cell layer hyperplasia, abnormal superficial mitosis, increased nuclear-cytoplasmic ratio, increased nuclear size, and hyperchromasia represent transformation-relevant dysplastic features in the atrophic epithelium of OSMF Their presence can be considered a high-risk feature for OSMF patients. The presence of these features can be considered a high-risk feature for patients. These findings have not been tested and authenticated using markers relevant to oral carcinogenesis

Methods

Results

Conclusion