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

<div><p>Background</p><p>The 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.</p><p>Method</p><p>Paraffin-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.</p><p>Results</p><p>Ki67 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%).</p><p>Conclusion</p><p>Ki67 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.</p></div

Correlation between Ki67, MVD and alpha SMA by Pearson’s rank correlation analysis.

<p>Correlation between Ki67, MVD and alpha SMA by Pearson’s rank correlation analysis.</p

Clinico-pathological details of oral submucous fibrosis patients.

<p>Clinico-pathological details of oral submucous fibrosis patients.</p

Comparison of Ki67, MVD and Alpha-SMA expression with normal, low-risk epithelial dysplasia and high-risk epithelial dysplasia.

<p>Comparison of Ki67, MVD and Alpha-SMA expression with normal, low-risk epithelial dysplasia and high-risk epithelial dysplasia.</p

Cases positive for a-SMA expression with the intensity of expression in OSMF-LRED, OSMF-HRED and NOM.

<p>Cases positive for a-SMA expression with the intensity of expression in OSMF-LRED, OSMF-HRED and NOM.</p

Ki67, CD105, and α-SMA expression supports the transformation relevant dysplastic features in the atrophic epithelium of oral submucous fibrosis - Fig 1

<p>Photomicrograph of LRED Showing a) Ki67 labeling index, b) CD105 (Neoangiogenesis) and c) α-SMA Expression (100X).</p

Ki67, CD105, and α-SMA expression supports the transformation relevant dysplastic features in the atrophic epithelium of oral submucous fibrosis - Fig 2

<p>Photomicrograph of HRED showing a) Ki67 labeling index, b) CD105 (Neoangiogenesis) and c) α-SMA Expression (100X).</p