Mammalian mastermind like 2 11q21 gene rearrangement in bronchopulmonary mucoepidermoid carcinoma

• Published in: Human pathology 2009-06, Vol.40 (6), p.854-860
• Main Authors: Achcar, Rosane De Oliveira Duarte, MD, Nikiforova, Marina N., MD, Dacic, Sanja, MD, PhD, Nicholson, Andrew G., DM, Yousem, Samuel A., MD
• Format: Article
• Language: English
• Subjects: Adenosarcoma - genetics; Adenosarcoma - pathology; Adult; Aged; Aged, 80 and over; Artificial chromosomes; Biological and medical sciences; Bronchial Neoplasms - genetics; Bronchial Neoplasms - pathology; Cancer; Carcinoma, Adenosquamous - genetics; Carcinoma, Adenosquamous - pathology; Carcinoma, Mucoepidermoid - genetics; Carcinoma, Mucoepidermoid - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; DNA-Binding Proteins - genetics; Female; Gene Fusion; Gene Rearrangement; Genes; Humans; In Situ Hybridization, Fluorescence; Investigative techniques, diagnostic techniques (general aspects); Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Molecular changes; Mucoepidermoid carcinoma; Nuclear Proteins - genetics; Oncogene Proteins, Fusion - genetics; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pneumology; Reverse Transcriptase Polymerase Chain Reaction; Studies; Transcription Factors - genetics; Translocation, Genetic; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2008.11.007

Summary The translocation t(11;19)(q21;p13) results in the gene fusion of mucoepidermoid carcinoma translocated 1–mammalian mastermind like 2 genes that is the major chromosomal abnormality observed in mucoepidermoid carcinomas of salivary glands but has not been studied in bronchopulmonary mucoepidermoid carcinoma. To investigate the importance of the mammalian mastermind like 2 gene rearrangement and mucoepidermoid carcinoma translocated 1–mammalian mastermind like 2 fusion gene in bronchopulmonary mucoepidermoid carcinoma tumorigenesis and its differential diagnosis with primary pulmonary non–small-cell carcinomas, we evaluated the presence of the mammalian mastermind like 2 gene rearrangement and the mucoepidermoid carcinoma translocated 1–mammalian mastermind like 2 fusion in formalin-fixed, paraffin-embedded tissue sections from 17 adult bronchopulmonary mucoepidermoid carcinoma, 16 adenosquamous carcinomas, 24 squamous cell carcinomas, and 41 primary adenocarcinomas by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction. We detected mammalian mastermind like 2 gene rearrangement by fluorescence in situ hybridization analysis in 13 (77%) of 17 bronchopulmonary mucoepidermoid carcinoma cases (10 of 10 being low grade and 3 of 7 being high grade). Reverse transcriptase polymerase chain reaction analysis confirmed positive fluorescence in situ hybridization results in 6 (43%) of 14 mucoepidermoid carcinoma cases. None of the squamous, adenosquamous, or adenocarcinoma cases revealed the mammalian mastermind like 2 gene rearrangement by fluorescence in situ hybridization, and the mucoepidermoid carcinoma translocated 1–mammalian mastermind like 2 fusion product by reverse transcriptase polymerase chain reaction was not identified specifically in our adenosquamous carcinoma cases. In conclusion, our study demonstrates that mammalian mastermind like 2 gene rearrangement and mucoepidermoid carcinoma translocated 1–mammalian mastermind like 2 fusion product can be detected by fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction analysis performed on low- and high-grade primary bronchopulmonary mucoepidermoid carcinoma and can be used to help discriminate low- and high-grade mucoepidermoid carcinoma from adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma mimics in histologically challenging cases.