Research Papers: Pathology:
Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements
Metrics: PDF 1216 views | HTML 1123 views | ?
Seok Joo Lee1, Woo Ick Yang1, Woo-Suk Chung2 and Sang Kyum Kim1
1 Department of Pathology, Yonsei University Medical Center, Seoul, South Korea
2 Department of Diagnostic Radiology, Konyang University Hospital, Daejeon, South Korea
Sang Kyum Kim, email:
Keywords: epithelioid hemangioendothelioma, TFE3, YAP1, CAMTA1, WWTR1, Pathology Section
Received: September 02, 2015 Accepted: January 21, 2016 Published: January 28, 2016
Epithelioid hemangioendotheliomas (EHEs) are vascular tumors of intermediate malignancy that can undergo high-grade malignant transformations. EHEs have been characterized by tumor-specific WW domain-containing transcription regulator 1(WWTR1)-calmodulin-binding transcription activator 1 (CAMTA1) translocations, and recently, a novel Yes-associated protein 1 (YAP1)-transcription factor E3 (TFE3) gene fusion was identified in EHEs. In this study, we examined the expression levels of TFE3 and CAMTA1 via immunohistochemical staining and identified chromosomal alterations using fluorescence in situ hybridization (FISH) assays and RT-PCR tests. Although all of the EHEs were CAMTA1-positive in immunohistochemical staining, only five out of 18 EHEs (27.78%) positively expressed nuclear TFE3. The five TFE3-positive EHEs exhibited TFE3 gene break-apart in FISH assays. YAP1-TFE3 gene fusions were confirmed by RT-PCR. Interestingly, we observed CAMTA1 gene break-apart in all of the five TFE3-positive EHEs via FISH assays, and four out of the five TFE3-positive EHEs exhibited WWTR1-CAMTA1 gene fusions via RT-PCR. These results indicate that these two chromosomal alterations are not mutually exclusive but compossible in EHEs. Finally, primary tumor sites in TFE3-positive EHEs consistently contained single masses (P = 0.0359) with larger sizes (P = 0.0550) compared to TFE3-negative EHEs. Similar to previous reports, we observed well-formed vessels more frequently in TFE3-positive EHEs than in TFE3-negative EHEs (P = 0.0441). In addition, TFE3-positive EHEs tended to more frequently demonstrate high-grade nuclear atypia (P = 0.0654) and hypercellularity (P=0.0987) than TFE3-negative EHEs. Thus, we have now established two clinically distinct subgroups of EHEs: TFE3-positive and TFE3-negative EHEs.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.