Evaluatıon Of Dıagnostıc And Prognostıc Role Of Cancer Stem Cells And Aldehyde Dehydrogenase Actıvıty In Dıfferent Salıvary Gland Tumors


Thesis Type: Doctorate

Institution Of The Thesis: Gazi University, Turkey

Approval Date: 2015

Thesis Language: English

Student: Alaa M. Shuibat

Supervisor: BENAY YILDIRIM

Abstract:

Salivary gland tumors exhibit a diverse range of histological appearance because of the various shapes and arrangements of the neoplastic cells which makes the diagnostic and prognostic predictions a real challenge. A subset of cells, tentatively called cancer stem cells (CSCs) have been associated with tumor initiation, drug resistance, and tumor aggressiveness. Recent evidence suggests that enhanced activity of aldehyde dehydrogenase 1 (ALDH 1), CD44, CD24, CD166, as hallmark of cancer stem cells. For that reason this study aims to determine the distribution of the cancer stem cell markers ALDH1, CD166, CD44 and CD24 among different benign, malignant salivary gland tumors as well as normal salivary gland tissues. 24 malignant salivary gland tumors (6 mucoepidermoid carcinoma, 6 polymorphous low grade adenocarcinoma, 8 adenoid cystic carcinoma, 2 carcinoma ex-pleomorphic adenoma, 2 acinic cell carcinoma) 24 benign salivary gland tumors (21 pleomorphic adenoma, 3 basal cell adenoma) and 7 normal salivary gland tissues from the archive of Gazi University Faculty of Dentistry were enrolled in the study. Demographic features and 7 years follow up data of patients were recorded. A total of 55 blocks have been immunohistochemically stained for CSCs markers ALDH1, CD44, CD24, and CD166. ALDH1 expression was down regulated in malignant tumors (P 0.034). Decreased ALDH expression was noted in high grade tumors. The lack of ALDH1 expression in adenoid cystic carcinomas (P 0.000) and basal call adenomas in relation to other tumors (P 0.026) were statistically significant. Malignant SG tumors displayed statistically significant up regulated CD166 expression (P 0.002). Loss of CD166 was determined both in metastasising/recurrent and high grade tumors in comparison to nonmetastisizin/ non-recurrent and low grade tumors. Diminishing CD44 expression was noted in benign and malignant tumors in descending order while metastisizing/recurrent tumor had higher CD44 expression in comparision to non-metastasizing / non-recurrent tumors. Benign SGT showed higher CD24 expression in comparison to malignant tumors. There was a higher CD24 expression in metastasising /recurrent tumors. Down regulation of ALDH expression by age also showed statistical significance (P 0.007). In conclusion there was a statistically significant up regulation of CD166 and down regulation of ALDH1 expression in malignant salivary gland tumors. This data suggested that these molecules could be useful markers for cancer stem cells in salivary gland tumors. Our results also supported the literature information that variations in expressions of these markers might be correlated with the prognosis of salivary gland tumors. The lack of ALDH1 expression in adenoid cystic carcinoma (Ad CC) suggested the potential role of this molecule as a diagnostic marker in differential diagnosis of Ad CC.