1. Comprehensive screening forMED12mutations in gynaecological mesenchymal tumours identified morphologically distinctive mixed epithelial and stromal tumours
- Author
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Chen Hui Lee, Yu-Chien Kao, Ming Chieh Lin, Kuan-Ting Kuo, Hsuan-Ying Huang, Cheng-Han Lee, Jen-Chieh Lee, Chang Tsu Yuan, and Wen Chih Huang
- Subjects
Adult ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Histology ,Genotype ,Genital Neoplasms, Female ,DNA Mutational Analysis ,Laser Capture Microdissection ,Biology ,Polymerase Chain Reaction ,Pathology and Forensic Medicine ,MED12 ,Young Adult ,03 medical and health sciences ,Exon ,0302 clinical medicine ,medicine ,Humans ,Adenomyosis ,Nuclear atypia ,YWHAE ,In Situ Hybridization, Fluorescence ,Aged ,Mediator Complex ,Splice site mutation ,Endometrial stromal sarcoma ,General Medicine ,Middle Aged ,medicine.disease ,Immunohistochemistry ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Adenosarcoma ,Cancer research ,Female ,Neoplasms, Connective and Soft Tissue - Abstract
Aims MED12 exon 2 mutations have been identified in most uterine leiomyomas and mammary fibroepithelial tumours. MED12 has not been genotyped in most other gynaecological mesenchymal tumours. The purpose of this study was to determine the prevalence of MED12 mutations in uncommon gynaecological mesenchymal tumours. Methods and results Sixty-eight uncommon gynaecological mesenchymal tumours were genotyped for MED12 exon 2, including 27 Mullerian adenosarcomas (including three tentatively diagnosed as ‘variant adenosarcomas’), six cellular angiofibromas, six aggressive angiomyxomas, five angiomyofibroblastomas, five superficial myofibroblastomas, five atypical polypoid adenomyomas, and 14 endometrial stromal sarcomas. Immunohistochemistry for CD10, myogenic markers, hormone receptors, MDM2, and CDK4, and fluorescence in-situ hybridization (FISH) for JAZF1, PHF1 and YWHAE rearrangement, were performed on selected cases. The three ‘variant adenosarcomas’ harboured MED12 exon 2 mutations (including p.L36R hotspot mutation, recurrent p.L39_A50del, and a novel splice site mutation). Three endometrial stromal sarcomas with JAZF1–SUZ12 or JAZF1–PHF1 fusion harboured unprecedented mutations (p.D54G in two, and p.Q48* in one). All remaining tumours were wild-type. The three MED12-mutated ‘variant adenosarcomas’ showed distinctive morphological features, including ‘fibromyomatous’ cytomorphology, a close association with adenomyosis, clustered thick-walled vessels, focal conspicuous hyalinization, and intralymphovascular tumour growth. Features of conventional adenosarcomas, including nuclear atypia, mitotic activity, periglandular condensation, and phyllodes-like architecture, were inconspicuous. All three cases showed immunoreactivity for desmin and hormone receptors, while being negative for MDM2 and CDK4; they showed no JAZF1, PHF1 or YWHAE rearrangement. Despite deep myoinvasion, these tumours followed an indolent clinical course. Conclusions These MED12-mutated adenosarcoma-like tumours might represent a distinct entity that requires more studies for its identification. MED12 exon 2 mutations seemed to have no significant role in other uncommon gynaecological mesenchymal tumours.
- Published
- 2017