Study of FHIT and WWOX expression in mucoepidermoid carcinoma and adenoid cystic carcinoma of salivary gland

• Published in: Oral oncology 2010-03, Vol.46 (3), p.195-199
• Main Authors: Dincer, Nazmiye, Tezel, Gaye Güler, Sungur, Arzu, Himmetoglu, Cigdem, Huebner, Kay, Güler, Gülnur
• Format: Article
• Language: English
• Subjects: Acid Anhydride Hydrolases - genetics; Acid Anhydride Hydrolases - metabolism; Adenoid cystic carcinoma; Adolescent; Adult; Aged; Basal-like phenotype; Biological and medical sciences; Carcinoma, Adenoid Cystic - genetics; Carcinoma, Adenoid Cystic - metabolism; Carcinoma, Mucoepidermoid - genetics; Carcinoma, Mucoepidermoid - metabolism; Cell Line, Tumor; Cell Transformation, Neoplastic; Child; Chromosome Fragile Sites; Chromosomes, Human, Pair 16; Chromosomes, Human, Pair 3; Female; FHIT; Genes, Tumor Suppressor; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Mucoepidermoid carcinoma; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Otolaryngology; Otorhinolaryngology. Stomatology; Oxidoreductases - genetics; Oxidoreductases - metabolism; Prognosis; Salivary gland cancer; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - metabolism; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; WW Domain-Containing Oxidoreductase; WWOX; Young Adult
• ISSN: 1368-8375; 1879-0593
• DOI: 10.1016/j.oraloncology.2009.12.003

Abstract Mucoepidermoid carcinoma (MEC) and adenoid cystic carcinoma (ACC) are salivary gland neoplasms with divergent morphological features and clinical behavior. ACC is a basaloid tumor whereas MEC is a glandular epithelial neoplasm. FHIT and WWOX are tumor suppressor genes that encompass the FRA3B and FRA16D fragile sites at chromosomes 3p14.2 and 16q23.3, respectively. In previous studies, we have shown concordant loss of Fhit and Wwox expression in breast cancer, with significantly more frequent loss in cancers of basal-like phenotype. To determine if there is a similar association in salivary gland neoplasms, we designed a study of MEC and ACC of salivary gland on tissue microarrays (TMA). TMAs were constructed from 25 MEC and 19 ACC of salivary gland. Fhit and Wwox protein expression was assessed by immunohistochemical staining of cores on TMAs. Correlations among immunohistochemical markers and histological type were determined by statistical analyses. Significantly reduced Fhit and Wwox expression was observed in ACC ( p = 0.002 and p < 0.001, respectively). The results suggest that, as for breast cancer, loss of Fhit and Wwox expression might have a role in the pathogenesis of basaloid differentiation in salivary gland neoplasms; alternatively, differences in chromatin structure at chromosome fragile regions might make fragile genes more accessible to DNA damage and rearrangement early during preneoplastic stages of basaloid cancers. Studies of basaloid tumors of other organ systems may show similar results and these findings may have implications for treatment modalities designed for basal-like tumors.