PMID- 24714697 OWN - NLM STAT- MEDLINE DCOM- 20141203 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 4 DP - 2014 TI - MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression. PG - e94399 LID - 10.1371/journal.pone.0094399 [doi] LID - e94399 AB - INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC) is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19) resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH) in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC), and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC). The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001) and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively). Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023) or disease-free survival (p = 0.027) as well as correlation between FLT1 and overall survival (p = 0.009). CONCLUSIONS: MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC. FAU - Zhu, Fen AU - Zhu F AD - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Wang, Weige AU - Wang W AD - Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. FAU - Hou, Yingyong AU - Hou Y AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Shi, Jindong AU - Shi J AD - The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China. FAU - Liu, Zilong AU - Liu Z AD - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - He, Deming AU - He D AD - Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Bai, Chunxue AU - Bai C AD - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Li, Shanqun AU - Li S AD - Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Jiang, Liyan AU - Jiang L AD - Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140408 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (DNA-Binding Proteins) RN - 0 (MAML2 protein, human) RN - 0 (Nuclear Proteins) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (Trans-Activators) RN - 0 (Transcription Factors) RN - EC 2.7.10.1 (FLT1 protein, human) RN - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-1) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Carcinoma, Mucoepidermoid/*genetics/mortality/pathology MH - DNA-Binding Proteins/*genetics MH - Female MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Staging MH - Nuclear Proteins/*genetics MH - Oncogene Proteins, Fusion/*genetics MH - Prognosis MH - Salivary Gland Neoplasms/*genetics/mortality/pathology MH - Trans-Activators MH - Transcription Factors/*genetics MH - Translocation, Genetic MH - Vascular Endothelial Growth Factor Receptor-1/*genetics MH - Young Adult PMC - PMC3979848 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/04/10 06:00 MHDA- 2014/12/15 06:00 PMCR- 2014/04/08 CRDT- 2014/04/10 06:00 PHST- 2014/01/23 00:00 [received] PHST- 2014/03/13 00:00 [accepted] PHST- 2014/04/10 06:00 [entrez] PHST- 2014/04/10 06:00 [pubmed] PHST- 2014/12/15 06:00 [medline] PHST- 2014/04/08 00:00 [pmc-release] AID - PONE-D-14-02260 [pii] AID - 10.1371/journal.pone.0094399 [doi] PST - epublish SO - PLoS One. 2014 Apr 8;9(4):e94399. doi: 10.1371/journal.pone.0094399. eCollection 2014.