TY - JOUR
T1 - Prognostic significance of the MDM2/HMGA2 ratio and histological tumor grade in dedifferentiated liposarcoma
AU - Yamashita, Kyoko
AU - Kohashi, Kenichi
AU - Yamada, Yuichi
AU - Akatsuka, Shinya
AU - Ikuta, Kunihiro
AU - Nishida, Yoshihiro
AU - Toyokuni, Shinya
AU - Oda, Yoshinao
N1 - Funding Information:
The authors would like to thank pathologist Dr. Shigeo Nakamura and Dr. Yoshie Shimoyama (Department of Pathology and Laboratory Medicine, Nagoya University Hospital), who kindly provided the case materials. This study was supported by JSPS KAKENHI grant numbers JP 16 K19079 (KY) and 19 K16570 (KY). This work was presented in part at the 108th Annual Meeting of the United States and Canadian Academy of Pathology in National Harbor in March 2019.
Funding Information:
JSPS KAKENHI, Grant/Award Numbers: 16K19079, 19K16570 Funding information
Funding Information:
The authors would like to thank pathologist Dr. Shigeo Nakamura and Dr. Yoshie Shimoyama (Department of Pathology and Laboratory Medicine, Nagoya University Hospital), who kindly provided the case materials. This study was supported by JSPS KAKENHI grant numbers JP 16 K19079 (KY) and 19 K16570 (KY). This work was presented in part at the 108th Annual Meeting of the United States and Canadian Academy of Pathology in National Harbor in March 2019.
Publisher Copyright:
© 2020 Wiley Periodicals LLC
PY - 2021/1
Y1 - 2021/1
N2 - Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well-differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra-tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good-prognosis and the poor-prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]-log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P <.001) and poor distant metastasis-free survival (DMFS) (P <.001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.
AB - Dedifferentiated liposarcoma (DDLPS) is a relatively common soft tissue sarcoma that results from the progression of well-differentiated liposarcoma (WDLPS). This study aimed to investigate the progression process and to clarify the pathological and genetic factors related to poor prognosis in DDLPS. In 32 DDLPS cases and five WDLPS cases, genetic factors were analyzed by custom comparative genomic hybridization (CGH) array, which was designed to densely cover gene regions known to be frequently amplified in WD/DDLPS. The analyses comparing primary and metastatic lesions and those comparing histologically different areas in the same tumor revealed intra-tumoral genetic heterogeneity and progression. According to a prognostic analysis comparing the good-prognosis and the poor-prognosis groups, we selected MDM2 and HMGA2 as candidate genes associated with poor and good prognosis, respectively. The ratios of the amplification or gain levels of MDM2 and HMGA2 expressed in log ratios (log[MDM2/HMGA2] = log[MDM2]-log[HMGA2]) were significantly associated with prognosis. An amplification or gain level of MDM2 that was more than twice that of HMGA2 (MDM2/HMGA2 > 2, log[MDM2/HMGA2] > 1) was strongly related to poor OS (P <.001) and poor distant metastasis-free survival (DMFS) (P <.001). In the pathological analysis of 44 cases of DDLPS, histological tumor grade, cellular atypia, and MDM2 immunoreactivity were related to overall survival (OS), while HMGA2 immunoreactivity tended to be associated with OS. Cellular atypia was also associated with DMFS. In conclusion, histological grade and MDM2 expression were determined to be prognostically important, and the MDM2/HMGA2 amplification or gain ratio was found to have significant prognostic value by the custom CGH array analysis.
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U2 - 10.1002/gcc.22899
DO - 10.1002/gcc.22899
M3 - Article
C2 - 33111425
AN - SCOPUS:85093985681
SN - 1045-2257
VL - 60
SP - 26
EP - 37
JO - Genes Chromosomes and Cancer
JF - Genes Chromosomes and Cancer
IS - 1
ER -
