TY - JOUR
T1 - Wilms' tumor 1 protein and estrogen receptor beta expression are associated with poor outcomes in uterine carcinosarcoma
AU - Guntupalli, Saketh R.
AU - Cao, Dengfeng
AU - Shroff, Rupal
AU - Gao, Feng
AU - Menias, Christine
AU - Stewart Massad, L.
AU - Powell, Matthew A.
AU - Mutch, David G.
AU - Thaker, Premal H.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878859042&partnerID=8YFLogxK
U2 - 10.1245/s10434-012-2838-9
DO - 10.1245/s10434-012-2838-9
M3 - Article
C2 - 23344579
AN - SCOPUS:84878859042
SN - 1068-9265
VL - 20
SP - 2373
EP - 2379
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 7
ER -