TY - JOUR
T1 - Anterior gradient protein 2 (AGR2) is an independent prognostic factor in ovarian high-grade serous carcinoma
AU - Darb-Esfahani, S.
AU - Fritzsche, F.
AU - Kristiansen, G.
AU - Weichert, W.
AU - Sehouli, J.
AU - Braicu, I.
AU - Dietel, M.
AU - Denkert, C.
PY - 2012/8
Y1 - 2012/8
N2 - Ovarian high-grade serous carcinoma (HGSC, type 2 ovarian carcinoma) is a poor prognosis cancer with limited therapeutic options. We aimed to investigate the expression pattern and prognostic potential of the metastasispromoting protein anterior gradient 2 (AGR2) in primary HGSC. Immunohistochemistry was applied to a cohort of 124 primary HGSCs using tissue microarrays. Additionally, in 48 type 1 carcinomas (low-grade serous (LGSC), endometrioid (EC), clear cell (CCC), and mucinous carcinoma (MC)), AGR2 expression was investigated in an exploratory approach. A strong expression of AGR2 was seen in 15 HGSCs (12.1 %) and was significantly linked to shortened overall survival (OS, p=0.011) and also for progression-free survival (PFS, p=0.001) in the setting of adjuvant platinum-based chemotherapy (CTX). Multivariate survival analysis including age, stage, and residual tumor after surgery revealed that AGR2 expression was an independent prognostic marker for OS (p=0.001) and PFS (p=0.001) in HGSC. In type 1 carcinomas, AGR2 was significantly increased as compared to HGSC (p=0.001) and was seen in subsets of all histological types, low-grade serous LGSC, EC, CCC, and MC. In particular, strong diffuse staining was seen in LGSC and MC. There was no association between AGR2 and estrogen receptor expression in ovarian type 1 or type 2 carcinomas. AGR2 expression identifies highly aggressive HGSC with a compromised prognosis for which novel therapeutic options are needed. Our data strongly support the further evaluation of AGR2 as a therapeutic target and a potential marker for response to platinum-based CTX in this tumor entity.
AB - Ovarian high-grade serous carcinoma (HGSC, type 2 ovarian carcinoma) is a poor prognosis cancer with limited therapeutic options. We aimed to investigate the expression pattern and prognostic potential of the metastasispromoting protein anterior gradient 2 (AGR2) in primary HGSC. Immunohistochemistry was applied to a cohort of 124 primary HGSCs using tissue microarrays. Additionally, in 48 type 1 carcinomas (low-grade serous (LGSC), endometrioid (EC), clear cell (CCC), and mucinous carcinoma (MC)), AGR2 expression was investigated in an exploratory approach. A strong expression of AGR2 was seen in 15 HGSCs (12.1 %) and was significantly linked to shortened overall survival (OS, p=0.011) and also for progression-free survival (PFS, p=0.001) in the setting of adjuvant platinum-based chemotherapy (CTX). Multivariate survival analysis including age, stage, and residual tumor after surgery revealed that AGR2 expression was an independent prognostic marker for OS (p=0.001) and PFS (p=0.001) in HGSC. In type 1 carcinomas, AGR2 was significantly increased as compared to HGSC (p=0.001) and was seen in subsets of all histological types, low-grade serous LGSC, EC, CCC, and MC. In particular, strong diffuse staining was seen in LGSC and MC. There was no association between AGR2 and estrogen receptor expression in ovarian type 1 or type 2 carcinomas. AGR2 expression identifies highly aggressive HGSC with a compromised prognosis for which novel therapeutic options are needed. Our data strongly support the further evaluation of AGR2 as a therapeutic target and a potential marker for response to platinum-based CTX in this tumor entity.
KW - AGR2
KW - High-grade serous carcinoma
KW - Ovarian
KW - Prognosis
UR - http://www.scopus.com/inward/record.url?scp=84867403102&partnerID=8YFLogxK
U2 - 10.1007/s00428-012-1273-4
DO - 10.1007/s00428-012-1273-4
M3 - Article
C2 - 22752467
AN - SCOPUS:84867403102
SN - 0945-6317
VL - 461
SP - 109
EP - 116
JO - Virchows Archiv
JF - Virchows Archiv
IS - 2
ER -
