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

Gynecol Oncol. 2003 Aug;90(2):248-57. doi: 10.1016/s0090-8258(03)00321-4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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