The Role of CD44 AND SOX-2 Cancer Stem cell Markers in The Development and Progression of Mucoepidermoid Carcinoma and Primary Squamous Cell Carcinoma of Salivary Glands

Abstract

One of the greatest difficulties to reach a successful treatment of mucoepidermoid carcinoma (MEC) and primary squamous cell carcinoma (PSSC) of salivary glands is the resistance to different therapeutic procedures which advocate the existence of a subpopulation of cancer stem cell (CSC). In salivary gland tumors the hypothesis of cancer stem cell has not been fully understood. Aim:To assess the expression of cancer stem cell markers CD44 and SOX2 in low and highgrades MEC and PSSC and to determine whether the expression of these markers can be used to predict tumor aggressiveness.Materials and Methods: 4μm sections were prepared from paraffin-embedded blocks of 16 samples of MEC and 16 samples of PSSC of salivary glands (8 low-grade and 8 high-grade carcinomas for each of them). Staining of each specimen with hematoxylin and eosin, CD44 and SOX2 was done.Results: All lesions of MEC and PSSC showed membranous CD44 and nuclear SOX2 expression. CD44 and SOX2 expression were significantly higher in high-grade tumors than in low-grade tumors. A strong positive correlation between CD44 and SOX2 expression was detected. Conclusion:Cancer stem cells can be identified in MEC and PSSC using CD44 and SOX2 markers and may participate in tumor aggressiveness. The present study also suggests that patients with MEC and PSSC may benefit from therapies that comprise a combination of the two markers.

Prognostic Significance of Cancer Stem Cell Markers in Patients With Salivary Gland Carcinomas

“…Solely an association of lower SOX2 expression with higher histopathologic grade was found in MEC patients. Contrary to the present study, Kamal32 revealed higher level of SOX2 expression in high-grade MECs. According to Thierauf et al,33 lack of expression of SOX2 marker mainly occurs in solid and high-grade AdCCs.…”

“…In line with our findings, Kamal's study also showed that all MECs were positive for CD44. 32 This study indicated a trend toward high CD133 expression in AdCC patients with poor outcomes such as high histopathologic grade, positive recurrence, lymph node involvement, positive distant metastasis, and death caused by disease. MEC tumors manifested a reduction of this marker with the outcomes as mentioned earlier.…”

Evaluation of CD44 Expression in Malignant Salivary Gland Tumors

“…The lowest and highest grade MEC revealed a high mean value in high grade MEC, whereas the lowest mean was in low grade MEC, with a statistically significant difference. In agreement with our findings, it was reported that the highest mean value was recorded in MEC high grade, while the lowest value was recorded in MEC low grade, with a statistically significant difference (20) . In accordance with our findings CD44 was demonstrated in high grade MEC as compared to low grade MEC, which was significantly over-expressed, with significant correlation with proliferative activity and motility (19) .…”

“…In comparison to low-grade tumors, strong CD44 expression was already reported in high-grade MEC. Notably, the authors reported significant associations between CD44 expressions with recurrences/metastases (20) .…”

“…In recent years , the role of CD44 in malignant SGTs has been characterized by a growing body of evidence; previous studies showed overexpression of CD44 in many malignant subtypes of SGTs, highlighting CD44's potential role as a biomarker for these malignancies and their aggressive behavior (20) .…”