Mucoepidermoid carcinoma of the cervix: another tumor with the t(11;19)-associated CRTC1-MAML2 gene fusion.
Mucoepidermoid carcinoma (MEC) of the uterine cervix is a controversial entity. By strict morphologic criteria, the tumor has features identical to those of salivary gland MEC and is characterized by nests composed of 3 cell types (epidermoid, intermediate, and mucin producing) in the absence of overt glandular differentiation. Nonetheless, the entity is not recognized in the current World Health Organization classification of cervical tumors. Given the morphologic similarity between MEC of the cervix and MEC of the salivary glands, we sought to determine if MEC of the cervix harbors the t(11;19)(q21;p13) characteristic of MEC of the major and minor salivary glands, a rearrangement that results in fusion of the cyclic adenosine 3',5' monophosphate coactivator CRTC1 to the Notch coactivator MAML2. We identified 7 cervical tumors from our departmental files and performed reverse transcription-polymerase chain reaction and fluorescence in situ hybridization-based molecular analysis for rearrangements of CRTC1 and MAML2; 14 conventional cervical adenosquamous carcinomas were used as controls. Analysis of the cervical MECs demonstrated a CRTC1-MAML2 fusion in 1 case, rearrangements of CRTC1 in 4 cases, and aberrations of MAML2 in 5 cases (rearrangements in 2 cases, amplification in 3 cases). All MEC showed aberrations of at least 1 of the loci, whereas none of the cervical adenosquamous carcinomas harbored rearrangements or amplification of either locus. Our results demonstrate that cervical tumors defined as MEC by strict morphologic criteria harbor genetic aberrations involving the genes characteristically rearranged in MEC of the salivary glands, and suggest that cervical MEC is an entity distinct from conventional cervical adenosquamous carcinoma. The development of drug therapy targeted to the genes rearranged in MEC underscores the importance of correct classification of cervical MEC because the diagnosis may hold therapeutic implications different from other cervical malignancies.
Lennerz
Jochen K M
JK
Divisions of Anatomic and Molecular Pathology, Washington University Medical Center, St Louis, MO, USA.
Perry
Arie
A
Mills
Jason C
JC
Huettner
Phyllis C
PC
Pfeifer
John D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000473:pathology*; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
C500984:CRTC1 protein, human; D004268:DNA-Binding Proteins; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors