Expression Of Fhit And Wwox In Salivary Gland Malignancies And Their Significance

[Objective]Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) which have divergent morphological features and clinical behavior are the most common salivary gland malignancies. FHIT and WWOX are tumor suppressor genes that have been found to span the FRA3B and FRA16D which are the most sensitive common chromosomal fragile site loci at chromosomes 3p14.2 and 16q23.3, respectively in the human genome. Recent studies indicate concordant loss of Fhit and Wwox expression in the process of breast cancer, with significantly more frequent loss in cancers of basal-like phenotype. In our study,we want to detect the expression and significance of Fhit and Wwox in salivary gland neoplasms(MEC and ACC)and analyze if there is a similar correlations in cancers of basal-like phenotype.[Methods]the expression of Fhit and Wwox proteins was investigated by immunohistochemistry SP method in 59 cases of salivary gland neoplasms, 35 MEC and 24 ACC,and 15 cases of normal salivary gland tissues. We divided MEC into two groups, high-grade and low/intermediate.; while ACC was divided into tubular/cribriform type and solid type. SPSS 17.0 Software was used to evaluate the correlation between the expression of Fhit and Wwox proteins and clinicopathological characteristics and the disparity in salivary gland neoplasms(MEC and ACC).[Results]We found reduced Fhit and Wwox proteins expression in salivary gland neoplasms(MEC and ACC) was significantly higher than that in normal salivary gland tissues (P<0.05).Reduced Fhit and Wwox expression in high-grade MEC was found more frequent than that in low/intermediate MEC.Statistically this difference does reach a significant level (P=0.03 and P=0.035, respectively). Reduced Fhit and Wwox expression in tubular/cribriform type of ACC was achieved more frequent than that in solid type of ACC. statistically significant results were observed(P=0.017,P=0.014,respectively). A significantly positive relationship was achieved between Fhit and Wwox in salivary gland neoplasms(MEC and ACC)(r=0.433,P=0.009;r=0.427,P=0.038).There was no relationship between the expression of Fhit and Wwox proteins and age,sex,tumor size and tumor site(P>0.05). Fhit and Wwox protein expression was decreased or lost significantly more common in ACC,a basaloid tumor(P=0.016 and P=0.039, respectively).[Conclusion]In accordance with previous studies, concordant lost or reduced Fhit and Wwox expression might play a important role in the initiation of salivary gland malignant neoplasms, with loss significantly more frequent in basal-like cancers ,similarly to breast cancer. Inactivation in common fragile tumor suppressor genes ,FHIT and WWOX ,which are more susceptible to environmental carcinogens, occur quite early in the development of many types of human cancers. Therefore, common fragile gene therapy could be a novel clinical target for the treatment and prevention of early-stage malignancies ,especially in basal-like cancers.