Altered Presence of Cancer Stem Cell ALDH1/2 in Oral Leukoplakias and Squamous Cell Carcinomas

Introduction: Cancer stem cells (CSCs) are responsible for initiating the process of carcinogenesis by enabling the self-renewal and self-proliferation of the cancer cells. This study aimed to investigate the presence of epithelial cells with cancer stem cells characteristics (ALDH+) in the early stages of oral precancerous lesions (Oral Leukoplakias) and the frequency of these cells in the different stages of oral squamous cell carcinomas (OSCCs).

Materials & methods: The aim of this study was the detection of the immunohistochemical pattern of expression of CSC protein-biomarker ALDH1&2 (sc-166362, Santa Cruz Co, Dallas, Texas, USA) in paraffin-embedded samples of 30 cases of leukoplakia of all degrees of dysplasia and 21 cases of oral squamous cell carcinomas (OSCC) of all degrees of differentiation compared to the histologically normal oral epithelium. The samples were retrieved from 2009-2019 from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. The samples were evaluated through a three-tier scale (positive cells Ι: 6-35%, ΙΙ: 36-70%, ΙΙΙ: 71-100%). Statistical analysis was performed through SPSS Pearson Chi-square, and the significance level was set at 0.05 (p=0.05). Results: The staining of ALDH1&2 was observed mildly in the cell membrane of cells in the stratum spinosum of the normal epithelium and the cell membrane of cells in the stratum basale of the normal epithelium, characteristically at the interface point with the basal membrane. ALDH1&2 were expressed significantly more in the OSCC than in the leukoplakia (p-value=0.0001) and the normal epithelium (p-value=0.0001). Mainly, ALDH1&2 were expressed significantly more in the severely and moderately dysplastic oral leukoplakia compared to the mildly dysplastic and non-dysplastic leukoplakia (p-value=0.001).

Discussion: The characteristic expression of ALDH in potentially malignant oral and OSCC lesions suggests the presence of CSCs and their possible implication in the early stages of oral tumorigenesis, even at the stage of oral leukoplakia.