Clonal and genetic relationship between individual components of mucoepidermoid carcinoma: X-chromosome inactivation assay and microsatellite analysis

• Published in: Human pathology 2016-10, Vol.56, p.114-122
• Main Authors: Wang, Wei, MS, Zou, Bingqing, MS, Zhu, Hongguang, PhD, Bao, Yun, MS
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Carcinoma, Mucoepidermoid - genetics; Carcinoma, Mucoepidermoid - pathology; Chromosomes; Chromosomes, Human, X; Deoxyribonucleic acid; DNA; Female; Genes; Genetic Predisposition to Disease; Heterogeneity; Humans; Individual components; Laser-capture microdissection; Loss of Heterozygosity; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Microsatellite Instability; Microsatellite Repeats; Mucoepidermoid carcinoma; Neoplasm Grading; Pathology; Phenotype; Polymerase chain reaction; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - pathology; Tumors; X Chromosome Inactivation
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2016.05.022

Mucoepidermoid carcinoma (MEC) is a common salivary gland malignancy characterized by genetic heterogeneity as well as cellular diversity of its neoplastic components which include mucinous cells, epidermoid cells and intermediate cells. The clonal and genetic relationship between each component has not been investigated before and it is unclear whether these three phenotypically distinct components differ genetically. Each component from all 21 cases was precisely microdissected and examined by microsatellite loss of heterozygosity (LOH) analysis with a panel of 5 microsatellite markers: D2S125, D5S417, D6S297, D6S1577 and D11S1311. In addition, X-chromosome inactivation assay was performed in the components from 18 female cases. The number of microdissected components varied from 2 to 3 depending on the quantity of each cell sub-population. Histopathological observation indicated that these three components shared an inseparable connection. Identical patterns of X-chromosome inactivation were shared among all the components in 9 of the 11 available informative cases. Of these 9 cases, 5 cases showed partially or totally discordant LOH patterns. Microsatellite analyses revealed discordant LOH patterns in 9 cases, 4 of which were corroborated to have identical X-chromosome inactivation patterns. Concordant LOH patterns were observed in all the components in 3 cases. These data suggest that heterologous components in most MECs are monoclonally originated. Individual components displayed identical and/or distinct LOH, implying that disparate genetic changes were implicated in the process of phenotypic divergence.