Prognostic implication of ezrin overexpression in myxofibrosarcomas.
BACKGROUND
The bases of tumorigenesis, progression, and metastasis remain obscure in myxofibrosarcoma. As a member of ezrin-radixin-moesin family, ezrin acts as a link between the cell membrane and actin cytoskeleton to integrate cell adhesion-mediated signaling. It is implicated in tumor progression and metastatic dissemination, and it is associated with adverse outcomes in several cancer types, including pediatric sarcomas.


METHODS
Ezrin immunostain could be assessed from tissue microarrays of 78 cases of primary localized myxofibrosarcomas and correlated with clinicopathological factors and patient survival. In two myxofibrosarcoma cell lines, ezrin mRNA expression was measured by real-time reverse transcriptase-polymerase chain reaction and the endogenous expression and activating phosphorylation of ezrin protein analyzed by Western blot test.


RESULTS
Ezrin overexpression was significantly associated with remarkable tumor necrosis (P = 0.025), increased histological grades (P = 0.037), advanced American Joint Committee on Cancer stages (P = 0.034), and higher mitotic rate (P < 0.001). Importantly, ezrin overexpression independently predicted inferior metastasis-free survival (P = 0.012, risk ratio = 4.083) and disease-specific survival (P = 0.0337, risk ratio = 4.537). The mRNA and total protein of ezrin in various cells were comparable in the expression level. Despite variation in abundance, phosphorylated ezrin at threonine(567) was detectable in myxofibrosarcoma cell lines but not in fibroblasts.


CONCLUSIONS
In primary myxofibrosarcomas, ezrin overexpression correlates with important prognostic elements and independently portends worse outcomes, highlighting the potential prognostic usefulness of ezrin in predicting tumor aggressiveness.
Huang
Hsuan-Ying
HY
Department of Pathology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung County 833, Taiwan. cfli.hyhuang@gmail.com
Li
Chien-Feng
CF
Fang
Fu-Min
FM
Tsai
Jen-Wei
JW
Li
Shau-Hsuan
SH
Lee
Yuan-Ting
YT
Wei
Huei-Min
HM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009236:Myxosarcoma / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D000099149:Ezrin