PMID- 20871214
OWN - NLM
STAT- MEDLINE
DCOM- 20101014
LR  - 20151119
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 34
IP  - 10
DP  - 2010 Oct
TI  - A distinctive subset of PEComas harbors TFE3 gene fusions.
PG  - 1395-406
LID - 10.1097/PAS.0b013e3181f17ac0 [doi]
AB  - Perivascular epithelioid cell neoplasms (PEComas) include the common renal 
      angiomyolipoma, pulmonary clear cell sugar tumor, lymphangioleiomyomatosis, and 
      less common neoplasms of soft tissue, gynecologic, and gastrointestinal tracts. 
      Recently, aberrant immunoreactivity for TFE3 protein (a sensitive and specific 
      marker of neoplasms harboring TFE3 gene fusions) has been reported in as many as 
      100% of PEComas; however, TFE3 gene status in these neoplasms has not been 
      systematically investigated. We used a fluorescence in situ hybridization (FISH) 
      break-apart assay to evaluate for evidence of TFE3 gene fusions in archival 
      material from 29 PEComas. These cases included 2 earlier published TFE3 
      immunoreactive nonrenal PEComas, 14 additional nonrenal PEComas, and 13 renal 
      angiomyolipomas with predominantly spindle or epithelioid morphology. Four 
      nonrenal PEComas (mean patient age 24 y) showed TFE3 gene rearrangements by FISH, 
      and all 4 of these showed strong positive (3+) TFE3 immunoreactivity using the 
      original validated overnight incubation protocol. Two of these cases had adequate 
      mRNA for RT-PCR analysis, but neither harbored the PSF-TFE3 gene fusion reported 
      earlier in 1 PEComa. In addition, a lung metastasis of a uterine PEComa showed 
      TFE3 gene amplification, an earlier unreported phenomenon. None of the other 24 
      PEComas (mean patient age 54 y) showed TFE3 gene alterations, though 4 exhibited 
      moderate positive (2+) TFE3 immunoreactivity. In contrast, using an automated 
      stainer, 2 of these 4 cases exhibited strong (3+) TFE3 immunoreactivity. All 
      PEComas with TFE3 genetic alterations immunolabeled strongly for Cathepsin K, 
      similar to other PEComas. In conclusion, a subset of lesions currently classified 
      as PEComas harbors TFE3 gene fusions. Although numbers are small, distinctive 
      features of these cases include a tendency to young age, the absence of 
      association with tuberous sclerosis, predominant alveolar architecture and 
      epithelioid cytology, minimal immunoreactivity for muscle markers, and strong 
      (3+) TFE3 immunoreactivity. Despite significant morphologic and 
      immunohistochemical overlap with other PEComas, PEComas harboring TFE3 gene 
      fusions may represent a distinctive entity.
FAU - Argani, Pedram
AU  - Argani P
AD  - Department of Pathology and Oncology, The Johns Hopkins Medical Intuitions, 
      Baltimore, MD, USA. pargani@jhmi.edu
FAU - Aulmann, Sebastian
AU  - Aulmann S
FAU - Illei, Peter B
AU  - Illei PB
FAU - Netto, George J
AU  - Netto GJ
FAU - Ro, Jae
AU  - Ro J
FAU - Cho, Hyun-yee
AU  - Cho HY
FAU - Dogan, Snjezana
AU  - Dogan S
FAU - Ladanyi, Marc
AU  - Ladanyi M
FAU - Martignoni, Guido
AU  - Martignoni G
FAU - Goldblum, John R
AU  - Goldblum JR
FAU - Weiss, Sharon W
AU  - Weiss SW
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Basic Helix-Loop-Helix Leucine Zipper Transcription Factors)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (RNA, Messenger)
RN  - 0 (TFE3 protein, human)
RN  - EC 3.4.22.38 (CTSK protein, human)
RN  - EC 3.4.22.38 (Cathepsin K)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/*genetics/metabolism
MH  - Biomarkers, Tumor/metabolism
MH  - Cathepsin K/metabolism
MH  - Child
MH  - Female
MH  - *Gene Fusion
MH  - Gene Rearrangement/*genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Perivascular Epithelioid Cell Neoplasms/*genetics/metabolism
MH  - RNA, Messenger/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2010/09/28 06:00
MHDA- 2010/10/15 06:00
CRDT- 2010/09/28 06:00
PHST- 2010/09/28 06:00 [entrez]
PHST- 2010/09/28 06:00 [pubmed]
PHST- 2010/10/15 06:00 [medline]
AID - 00000478-201010000-00001 [pii]
AID - 10.1097/PAS.0b013e3181f17ac0 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2010 Oct;34(10):1395-406. doi: 10.1097/PAS.0b013e3181f17ac0.