PMID- 35034038
OWN - NLM
STAT- MEDLINE
DCOM- 20220621
LR  - 20230922
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 46
IP  - 7
DP  - 2022 Jul 1
TI  - Molecular Characterization of Dermatofibrosarcoma Protuberans: The 
      Clinicopathologic Significance of Uncommon Fusion Gene Rearrangements and Their 
      Diagnostic Importance in the Exclusively Subcutaneous and Circumscribed Lesions.
PG  - 942-955
LID - 10.1097/PAS.0000000000001866 [doi]
AB  - The clinicopathologic relevance of various gene rearrangements underlying 
      dermatofibrosarcoma protuberans (DFSP) remains insufficiently characterized. In 
      188 DFSPs, we determined PDGFB, COL1A1, PDGFD, COL6A3, and EMILIN2 rearrangements 
      by fluorescence in situ hybridization (FISH). The clinicopathologic significance 
      of rearrangement types and factors related to recurrence and metastasis were 
      statistically analyzed. In all, classic PDGFB rearrangement, cryptic COL1A1-PDGFB 
      fusion, and PDGFD rearrangement were identified in 172 (91.4%), 8 (4.3%), and 8 
      (4.3%: 4 COL6A3-PDFGD, 4 EMILIN2-PDGFD) cases, respectively. In an index DFSP 
      harboring the cryptic fusion, the COL1A1-PDGFB transcript was confirmed by both 
      RNA sequencing and reverse transcription-polymerase chain reaction. In comparison 
      with cases harboring classic PDGFB rearrangement, cryptic PDGFB-rearranged DFSPs 
      usually exhibited higher 5'-COL1A1 copy numbers. In a combined reappraisal of 
      published and current cases, COL6A3-PDGFD-positive DFSPs (n=16) predominated in 
      females (n=14, 88%) and torso (n=14, 88%), especially the breast (n=7, 44%); 
      EMILIN2-PDGFD-positive DFSPs (n=6) preferentially demonstrated near exclusively 
      subcutaneous growth (n=5, 83%) and fibrosarcomatous transformation (n=5, 83%). In 
      our cohort, local recurrence was related to fibrosarcomatous variant (P=0.029, 
      odds ratio=3.478) and head and neck location (P=0.046, odds ratio=3.508). Distant 
      metastasis only occurred in the fibrosarcomatous variant (9/73, 12.3%) but not in 
      other cases. In conclusion, 8.6% of DFSPs are negative for PDGFB break-apart 
      FISH, which, especially those with challenging subcutaneous and circumscribed 
      manifestation, require complementary diagnosis by FISH assays targeting COL1A1 
      and PDGFD. The types of fusion gene rearrangements, head and neck location, and 
      fibrosarcomatous transformation may account for clinicopathologic and prognostic 
      variations in DFSPs and warrant future independent validation.
CI  - Copyright (c) 2022 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Lee, Pei-Hang
AU  - Lee PH
AD  - Departments of Anatomical Pathology.
FAU - Huang, Shih-Chiang
AU  - Huang SC
AD  - Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital, Chang Gung 
      University, College of Medicine.
AD  - Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung 
      University, Taoyuan.
FAU - Wu, Pao-Shu
AU  - Wu PS
AD  - Department of Pathology, MacKay Memorial Hospital.
AD  - Mackay Junior College of Medicine, Nursing, and Management.
FAU - Tai, Hui-Chun
AU  - Tai HC
AD  - Department of Pathology, Changhua Christian Hospital, Changhua.
FAU - Lee, Chih-Hung
AU  - Lee CH
AD  - Dermatology.
FAU - Lee, Jen-Chieh
AU  - Lee JC
AD  - Department and Graduate Institute of Pathology, National Taiwan University 
      Hospital, National Taiwan University College of Medicine.
FAU - Kao, Yu-Chien
AU  - Kao YC
AD  - Department of Pathology, Shuang Ho Hospital, Taipei Medical University.
AD  - Department of Pathology, School of Medicine, College of Medicine, Taipei Medical 
      University.
FAU - Tsai, Jen-Wei
AU  - Tsai JW
AD  - Department of Pathology, E-DA Hospital, I-Shou University.
FAU - Hsieh, Tsung-Han
AU  - Hsieh TH
AD  - Joint Biobank, Office of Human Research, Taipei Medical University, Taipei.
FAU - Li, Chien-Feng
AU  - Li CF
AD  - Department of Medical Research, Chi-Mei Medical Center.
FAU - Li, Wan-Shan
AU  - Li WS
AD  - Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
FAU - Liu, Ting-Ting
AU  - Liu TT
AD  - Departments of Anatomical Pathology.
AD  - Department of Medical Laboratory Science, I-Shou University, Kaohsiung.
FAU - Su, Yu-Li
AU  - Su YL
AD  - Division of Medical Oncology, Department of Internal Medicine, Kaohsiung Chang 
      Gung Memorial Hospital and Chang Gung University College of Medicine.
FAU - Yu, Shih-Chen
AU  - Yu SC
AD  - Departments of Anatomical Pathology.
FAU - Huang, Hsuan-Ying
AU  - Huang HY
AD  - Departments of Anatomical Pathology.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220117
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Collagen
MH  - *Dermatofibrosarcoma/diagnosis/genetics/pathology
MH  - Female
MH  - *Fibrosarcoma/genetics
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Oncogene Proteins, Fusion/genetics
MH  - Proto-Oncogene Proteins c-sis/genetics
MH  - *Skin Neoplasms/pathology
COIS- Conflicts of Interest and Source of Funding: Sponsored in part by Ministry of 
      Science and Technology, Taiwan (108-2320-B-182A-017-MY3 to H.-Y.H.) and Chang 
      Gung Hospital (CORPG8K0051, CMRPG8L0371 to H.-Y.H.). The authors have disclosed 
      that they have no significant relationships with, or financial interest in, any 
      commercial companies pertaining to this article.
EDAT- 2022/01/17 06:00
MHDA- 2022/06/22 06:00
CRDT- 2022/01/16 21:10
PHST- 2022/01/17 06:00 [pubmed]
PHST- 2022/06/22 06:00 [medline]
PHST- 2022/01/16 21:10 [entrez]
AID - 00000478-202207000-00007 [pii]
AID - 10.1097/PAS.0000000000001866 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2022 Jul 1;46(7):942-955. doi: 10.1097/PAS.0000000000001866. 
      Epub 2022 Jan 17.