Wilms' tumor 1 protein and estrogen receptor beta expression are associated with poor outcomes in uterine carcinosarcoma.
BACKGROUND
Uterine carcinosarcoma (CS) is an aggressive malignancy. Increased expression of Wilms' tumor 1 (WT1) protein and estrogen receptor beta (ER-β) protein is associated with worse outcomes in gynecologic cancers; therefore, we sought to assess this association in CS patients.


METHODS
A retrospective analysis was conducted for women diagnosed with uterine CS from departmental databases. WT1/ER-β expression was determined by immunohistochemical staining and scoring of specimens. Univariate and multivariate models were used to correlate progression-free survival (PFS) and overall survival (OS) with WT1/ER-β expression and clinicopathologic factors.


RESULTS
Ninety four patients had mean follow-up of 27 months. Postoperative treatments included chemotherapy for 52 (55 %) subjects and radiotherapy for 25 (27 %). Sixty-four (68 %) and 74 (79 %) tumor samples expressed WT1 and ER-β by immunohistochemistry, respectively. On univariate analysis, stage (p = .02) and lower uterine segment invasion (LUSI) (p = .001) were associated with decreased PFS. Only stage (p = .003) was linked to OS. In the total sample, increased WT1 expression was marginally associated with impaired PFS (p = .07) and OS (p = .09) but ER-β expression was not associated with PFS (p = .89) or OS (p = .30). WT1 and ER-β concurrent expression was associated with impaired OS (p = .02) and PFS (p = .02). On multivariate analysis, LUSI was a significant prognostic factor for PFS [hazard ratio (HR) 2.21, 95 % confidence interval (CI) = 1.12-4.32, p = .03] and stage for OS (HR 3.20, 95 % CI = 1.23-8.35, p = .02). Increased WT1/ER-β expression was associated with impaired OS (HR 1.31, 95 % CI = 1.02-1.69, p = .04).


CONCLUSIONS
Concurrent increased WT1 and ER-β expression impairs prognosis for women with uterine CS. Further research is warranted to define how relevant pathways interact and whether targeting these pathways improves OS.
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Colorado School of Medicine at Denver, Denver, CO, USA. saketh.guntupalli@ucdenver.edu
Saketh R
SR
Guntupalli
Dengfeng
D
Cao
Rupal
R
Shroff
Feng
F
Gao
Christine
C
Menias
L
L
Stewart Massad
Matthew A
MA
Powell
David G
DG
Mutch
Premal H
PH
Thaker
D000368:Aged; D002296:Carcinosarcoma / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D007044:Hysterectomy; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D012189:Retrospective Studies; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D025721:WT1 Proteins / Q000378:metabolism*
D047629:Estrogen Receptor beta; D025721:WT1 Proteins; C583751:WT1 protein, human