AlphaV- and beta1-integrin subunits are commonly expressed in malignant effusions from ovarian carcinoma patients.

Abstract

OBJECTIVE:

The objective was to study expression of alphav- and beta1-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 alphav- and beta1-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 alphav- and beta1-integrin subunits was detected in carcinoma cells in 116/121 (96%) and 113/121 (93%) effusions, respectively. alphav protein expression was limited to carcinoma cells. IB and FCM confirmed IHC results. mRNA for alphav- and beta1-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 alphav mRNA (P = 0.042) and beta1 protein (P = 0.023). beta1 protein expression in effusions was more frequently detected in better-differentiated tumors (P = 0.006). alphav-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 beta1-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, alphav protein was uniformly present, while beta1 expression was limited to 15/30 (50%) specimens. As in effusions, protein expression of alphav subunit was cancer-specific, while beta1 protein was detected also in stromal fibroblasts and endothelial cells.

CONCLUSIONS:

The alphav- and beta1-integrin subunits are frequently expressed in ovarian carcinoma cells in effusions, and the alphav-integrin subunit is a powerful diagnostic marker for carcinoma cells. The reduced expression of the beta1-integrin subunit in solid lesions may be attributed to the role of other subunits at these stages, such as the beta3 subunit as part of the alphavbeta3-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.

• Authors: Ben Davidson, Iris Goldberg, Reuven Reich, Liora Tell, Hiep Phuc Dong, Claes G Trope', Bjørn Risberg, Juri Kopolovic
• Journal: Gynecologic oncology (Gynecol Oncol) Vol. 90 Issue 2 Pg. 248-57 (Aug 2003) ISSN: 0090-8258 [Print] United States
• PMID: 12893184 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Integrin alphaV
• Integrin beta1
• RNA, Messenger

Topics

• Adult
• Aged
• Aged, 80 and over
• Ascitic Fluid (genetics, metabolism)
• Biomarkers, Tumor (biosynthesis, genetics)
• Cohort Studies
• Female
• Flow Cytometry
• Humans
• Immunoblotting
• Immunohistochemistry
• In Situ Hybridization
• Integrin alphaV (biosynthesis, genetics)
• Integrin beta1 (biosynthesis, genetics)
• Middle Aged
• Neoplasm Metastasis
• Ovarian Neoplasms (genetics, metabolism, pathology)
• RNA, Messenger (biosynthesis, genetics)