PMID- 31634336
OWN - NLM
STAT- MEDLINE
DCOM- 20201123
LR  - 20201123
IS  - 1728-7731 (Electronic)
IS  - 1726-4901 (Linking)
VI  - 82
IP  - 12
DP  - 2019 Dec
TI  - Gene amplification and tumor grading in parosteal osteosarcoma.
PG  - 889-894
LID - 10.1097/JCMA.0000000000000211 [doi]
AB  - BACKGROUND: Parosteal osteosarcoma (POS) is a unique low grade osteosarcoma. Two 
      separate oncogenes, MDM2 and CDK4, are specifically amplified in POS. Its 
      clinical behavior is usually indolent. In some occasions, it may progress to high 
      grade and become fatal. Malignant transformation with high grade differentiation 
      is the most reliable indicator to predict its aggressiveness and metastatic 
      potential. This study is to discover the relationship between gene amplification 
      and grading. METHODS: Retrospective analysis of MDM2/CDK4 
      expression/amplification using immunostaining, multiplex quantitative polymerase 
      chain reaction (MQPCR) and fluorescence in situ hybridization (FISH) were studied 
      on 14 patients with recurrent POS. RESULTS: Forty tumor specimens in 
      formalin-fixed paraffin-embedded blocks from 14 patients of POS were included in 
      this study. Twenty-seven tumors are low-grade, 13 are high-grade. All POS showed 
      increased expression of both MDM2 and CDK4 proteins, but not those from 
      conventional osteosarcoma. Except some tumors were non-informative (poor DNA 
      quality), the rest of POS had a marked increase of MDM2 and CDK4 genes copies by 
      MQPCR, and confirmed by MDM2 FISH. Moreover, the folds of amplification increase 
      as tumors progress. And, the amplification folds in high-grade POS are 
      consistently higher than those of conventional ones. CONCLUSION: FISH and MQPCR 
      are both useful assays for estimating oncogene amplification status in bone 
      tumors. Amplification levels of MDM2 and CDK4 are related to tumor grading and 
      progression. Molecular determination of gene amplification status can be a 
      reliable alternative for predicting clinical behavior of POS at small biopsies.
FAU - Chen, Paul Chih-Hsueh
AU  - Chen PC
AD  - Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
AD  - Therapeutical and Research Center of Musculoskeletal tumor, Department of 
      Orthopedics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
FAU - Yen, Chueh-Chuan
AU  - Yen CC
AD  - Therapeutical and Research Center of Musculoskeletal tumor, Department of 
      Orthopedics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
AD  - Division of Hematology and Oncology, Department of Medicine, Taipei Veterans 
      General Hospital, Taipei, Taiwan, ROC.
AD  - Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, 
      Taiwan, ROC.
FAU - Hung, Giun-Yi
AU  - Hung GY
AD  - Therapeutical and Research Center of Musculoskeletal tumor, Department of 
      Orthopedics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
AD  - Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
FAU - Pan, Chin-Chen
AU  - Pan CC
AD  - Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
AD  - Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, 
      Taiwan, ROC.
FAU - Chen, Wei-Ming
AU  - Chen WM
AD  - Therapeutical and Research Center of Musculoskeletal tumor, Department of 
      Orthopedics, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
AD  - Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, 
      Taiwan, ROC.
AD  - Department of Orthopedics, Taipei-Veterans General Hospital, Taipei, Taiwan, ROC.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - J Chin Med Assoc
JT  - Journal of the Chinese Medical Association : JCMA
JID - 101174817
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.11.22 (CDK4 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Bone Neoplasms/*genetics/pathology
MH  - Child
MH  - Cyclin-Dependent Kinase 4/*genetics
MH  - Female
MH  - *Gene Amplification
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Multiplex Polymerase Chain Reaction
MH  - Neoplasm Grading
MH  - Osteosarcoma, Juxtacortical/*genetics/pathology
MH  - Proto-Oncogene Proteins c-mdm2/*genetics
MH  - Retrospective Studies
MH  - Young Adult
EDAT- 2019/10/22 06:00
MHDA- 2020/11/24 06:00
CRDT- 2019/10/22 06:00
PHST- 2019/10/22 06:00 [pubmed]
PHST- 2020/11/24 06:00 [medline]
PHST- 2019/10/22 06:00 [entrez]
AID - 10.1097/JCMA.0000000000000211 [doi]
PST - ppublish
SO  - J Chin Med Assoc. 2019 Dec;82(12):889-894. doi: 10.1097/JCMA.0000000000000211.