ALDH1 Immunohistochemical expression and its association with tumor budding in oral squamous cell carcinoma of gingivobuccal complex

ABSTRACT Background: Aldehyde dehydrogenase 1 is a potential biomarker for cancer stem cells (CSCs), pertinent to tumorigenesis and treatment resistance, whereas tumor buds (TB) are small nests of tumor cells scattered in the stroma of tumor front. This study evaluated the interrelationship of TBs with CSCs in oral squamous cell carcinoma (OSCC) cases of gingivobuccal complex. Methods: An immunohistochemical study was conducted on paraffin-embedded sections of 50 cases of OSCC of gingivobuccal complex with Pan-CK for TB and ALDH1 for CSCs. Correlations were assessed between the semiquantitative scoring for immunohistochemical expression of ALDH1 and tumor budding intensity. Statistical evaluation was performed by the Chi-square test, and cutoff score was determined by employing ROC curve. Results: A significant correlation of ALDH1 expression was attained between the groups both inside ( P = 0.031) and outside ( P = 0.028) the budding area, reflecting a spatial distribution of CSCs in the tumor front. The ROC curve analysis suggested a cutoff value of 11%-50% ALDH1 expression inside TB area, demonstrating 76% of sensitivity and specificity of 63%, which may better predict aggressive behavior and poorer prognosis than TB alone in OSCC. Conclusion: ALDH1 expression inside and outside the budding area correlated significantly with TB intensity, suggesting that TBs have CSCs-like phenotype predisposing to migratory and invasive properties.