Expression of the FUT2 gene and CD44 marker in patients with oral lesions

ENSINCK A; LEBENSOHN N; VALLES M; COTORRUELO C; BIONDI C

Amsterdam

Congreso; 23rd Regional Congress of the International Society of Blood Transfusion; 2013

International Society of Blood Transfusion

Background: The mechanisms of aberrant expression of blood-group antigens are not clear in all cases. It has been demonstrated in a number of earlier studies on the etiology and pathogenesis of certain diseases that the patients' secretor status (ABO (H) blood group antigens) may probably be a factor influencing of the development of systemic oral diseases. One of the genes involved in tumour processes is CD44 which appears to be one of the most promising candidates as a cancer diagnosis marker. Aim: To investigate the FUT 2 gene, the secretor status and the expression of CD44 protein in epithelial cells obtain from saliva samples from patients with oral lesions (benign, pre-cancerous and cancerous lesions). Methods: Patients with benign oral lesions showed hyperplasia caused by diverse agents such as infectious, inflammatory, traumatic, hormonal, and drugs. The premalignant lesions included leukoplakia and lichen planus. The malignant lesions studied were squamous cell carcinoma. Appropriate informed consent was obtained from all subjects and all procedures were performed according to the ethical standards established by the University of Rosario. In total 188 subjects were examined, half of whom suffered from oral lesions, while the other half were the healthy control group. In order to establish the secretor status we analyzed their saliva by the agglutination inhibition technique We analyzed polymorphisms of the FUT2 gene by allele specific oligonucleotide? polymerase chain reaction. The FUT2 gene encodes the á(1,2) fucosyltransferase (Se enzyme) that regulates the expression of ABH antigens in secretions. We also investigate by confocal microscopy, the expression of CD44 protein in epithelial cells obtained from saliva samples from these patients. Results: The 79.5 % of the healthy individuals studied posses the Se gene (FUT 2) that governs the secretion of water-soluble ABH antigens into saliva. We found a higher intensity of oral disease in the non-secretor group (OR = 3.44). 51 % of the patients with oral pre-cancerous and cancerous lesions were non-secretors, in contrast with the healthy population. We observed a marginal association between secretor status and these lesions. The results obtained also showed fluorescence corresponding to the presence of CD44 protein in samples from patients diagnosed with cancer and precancer. A higher intensity was observed in individuals with a pathological diagnosis of squamous cell carcinoma. In contrast, samples from patients with benign lesions showed no fluorescence images as samples of the control group. Conclusions: Our study suggests that the lack of wild type FUT2 gene and a nonsecretor status appear to be an associated risk marker for the development of oral cancer in patients with oral lesions. Several mechanisms, based on the properties of CD44 as the major hyaluronan CD44 in squamous cell carcinomas receptor and as a signal transmitter and growth presenting molecule, have been proposed to explain the role of elevated CD44 expression during tumour development and progression. CD44 might be a good candidate as a predictor of prognosis in this group of cancers. Further follow-up studies are required to clarify the role of predictive markers of risk in precursor lesions of oral cancer.