TY - JOUR
T1 - αv- and β1-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients
AU - Davidson, Ben
AU - Goldberg, Iris
AU - Reich, Reuven
AU - Tell, Liora
AU - Dong, Hiep Phuc
AU - Trope', Claes G.
AU - Risberg, Bjørn
AU - Kopolovic, Juri
PY - 2003/8/1
Y1 - 2003/8/1
N2 - Objective. The objective was to study expression of αv- and β1-integrin subunits in effusions, primary tumors, and solid metastases of ovarian carcinoma patients, as well as to evaluate its potential association with previously studied metastasis-associated molecules and clinicopathologic parameters. Methods. Sections from 121 malignant effusions and 30 corresponding primary and metastatic lesions were evaluated for protein expression of the αv- and β1-integrin subunits using immunohistochemistry (IHC). A subset of effusions was additionally studied using immunoblotting (IB) and flow cytometry (FCM). mRNA in situ hybridization (ISH) was performed in 58 effusions and 30 biopsies. Results. Protein expression of αv- and β1-integrin subunits was detected in carcinoma cells in 116/121 (96%) and 113/121 (93%) effusions, respectively. αv protein expression was limited to carcinoma cells. IB and FCM confirmed IHC results. mRNA for αv- and β1-integrin subunits was detected in carcinoma cells in 37/58 (64%) and 33/58 (57%) effusions, respectively. Both protein and mRNA expression were higher in peritoneal effusions, significantly for αv mRNA (P = 0.042) and β1 protein (P = 0.023). β1 protein expression in effusions was more frequently detected in better-differentiated tumors (P = 0.006). αv-integrin subunit expression correlated with that of the previously studied matrix metalloproteinase-9 (MMP-9) (P = 0.006) and the MMP inducer EMMPRIN (P = 0.001). Expression of β1-integrin subunit showed an association with that of EMMPRIN (P = 0.029), basic fibroblast growth factor (P < 0.001), and the MMP inhibitor TIMP-2 (P = 0.025). In carcinoma cells of solid lesions, αv protein was uniformly present, while β1 expression was limited to 15/30 (50%) specimens. As in effusions, protein expression of αv subunit was cancer-specific, while β1 protein was detected also in stromal fibroblasts and endothelial cells. Conclusions. The αv- and β1-integrin subunits are frequently expressed in ovarian carcinoma cells in effusions, and the αv-integrin subunit is a powerful diagnostic marker for carcinoma cells. The reduced expression of the β1-integrin subunit in solid lesions may be attributed to the role of other subunits at these stages, such as the β3 subunit as part of the αvβ3-vitronectin receptor. The high expression of integrin subunits with a role of binding mesothelium, invasion, and angiogenesis in carcinoma cells in both peritoneal and pleural effusions suggests that cells at both sites have metastatic potential.
AB - Objective. The objective was to study expression of αv- and β1-integrin subunits in effusions, primary tumors, and solid metastases of ovarian carcinoma patients, as well as to evaluate its potential association with previously studied metastasis-associated molecules and clinicopathologic parameters. Methods. Sections from 121 malignant effusions and 30 corresponding primary and metastatic lesions were evaluated for protein expression of the αv- and β1-integrin subunits using immunohistochemistry (IHC). A subset of effusions was additionally studied using immunoblotting (IB) and flow cytometry (FCM). mRNA in situ hybridization (ISH) was performed in 58 effusions and 30 biopsies. Results. Protein expression of αv- and β1-integrin subunits was detected in carcinoma cells in 116/121 (96%) and 113/121 (93%) effusions, respectively. αv protein expression was limited to carcinoma cells. IB and FCM confirmed IHC results. mRNA for αv- and β1-integrin subunits was detected in carcinoma cells in 37/58 (64%) and 33/58 (57%) effusions, respectively. Both protein and mRNA expression were higher in peritoneal effusions, significantly for αv mRNA (P = 0.042) and β1 protein (P = 0.023). β1 protein expression in effusions was more frequently detected in better-differentiated tumors (P = 0.006). αv-integrin subunit expression correlated with that of the previously studied matrix metalloproteinase-9 (MMP-9) (P = 0.006) and the MMP inducer EMMPRIN (P = 0.001). Expression of β1-integrin subunit showed an association with that of EMMPRIN (P = 0.029), basic fibroblast growth factor (P < 0.001), and the MMP inhibitor TIMP-2 (P = 0.025). In carcinoma cells of solid lesions, αv protein was uniformly present, while β1 expression was limited to 15/30 (50%) specimens. As in effusions, protein expression of αv subunit was cancer-specific, while β1 protein was detected also in stromal fibroblasts and endothelial cells. Conclusions. The αv- and β1-integrin subunits are frequently expressed in ovarian carcinoma cells in effusions, and the αv-integrin subunit is a powerful diagnostic marker for carcinoma cells. The reduced expression of the β1-integrin subunit in solid lesions may be attributed to the role of other subunits at these stages, such as the β3 subunit as part of the αvβ3-vitronectin receptor. The high expression of integrin subunits with a role of binding mesothelium, invasion, and angiogenesis in carcinoma cells in both peritoneal and pleural effusions suggests that cells at both sites have metastatic potential.
KW - Adhesion molecules
KW - Immunohistochemistry
KW - Integrins
KW - mRNA in situ hybridization
KW - Ovarian carcinoma
KW - Serous effusions
UR - http://www.scopus.com/inward/record.url?scp=0042922958&partnerID=8YFLogxK
U2 - 10.1016/S0090-8258(03)00321-4
DO - 10.1016/S0090-8258(03)00321-4
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
C2 - 12893184
AN - SCOPUS:0042922958
SN - 0090-8258
VL - 90
SP - 248
EP - 257
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -