A link between the expression of the stem cell marker HMGA2, grading, and the fusion CRTC1-MAML2 in mucoepidermoid carcinoma.
Recently, the concept of cancer stem cells and their expression of embryonic stem cell markers has gained considerable experimental support. In this study, we examined the expression of one such marker, the high-mobility group AT-hook 2 gene (HMGA2) mRNA, in 53 formalin-fixed, paraffin-embedded mucoepidermoid carcinomas (MEC) and four normal parotid tissues using quantitative real-time RT-PCR (qPCR). MECs are often characterized by the fusion gene CRTC1-MAML2, the detection of which is an important tool for the diagnosis and prognosis of MEC. For detection of the CRTC1-MAML2 fusion transcript, we performed RT-PCR. The mean expression level of HMGA2 was higher in fusion negative (302.8 +/- 124.4; n = 14) than in positive tumors (67.3 +/- 13.1; n = 39). Furthermore, the fusion-negative tumors were often high-grade tumors and the HMGA2 expression level rose with the tumor grade (low: 43.7 +/- 11.0, intermediate: 126.2 +/- 28.3, and high: 271.2 +/- 126.5). A significant difference was found in the HMGA2 expression levels between the different grading groups (one-way ANOVA, P = 0.04) and among the fusion-negative and -positive tumors (t-test, P = 0.05), indicating that the expression level of HMGA2 was closely linked to grading, the presence/absence of the CRTC1-MAML2 fusion, and the tumor behavior of MECs. These findings offer further evidence for the theory that the MEC group comprises two subgroups: one group with the CRTC1-MAML2 fusion, which is a group with a moderate aggressiveness and prognosis, and the other group lacking that fusion corresponding to an increased stemness, and thus, higher aggressiveness and worse prognosis.
Fehr
André
A
Center for Human Genetics, University of Bremen, Bremen, Germany.
Meyer
Anke
A
Heidorn
Klaus
K
Röser
Kerstin
K
Löning
Thomas
T
Bullerdiek
Jörn
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D025743:HMGA2 Protein / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis / Q000235:genetics*; D010306:Parotid Gland / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D055815:Young Adult
C500984:CRTC1 protein, human; D004268:DNA-Binding Proteins; D025743:HMGA2 Protein; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors