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Expression of matrix metalloproteinase-26 and tissue inhibitors of metalloproteinase-3 and -4 in normal ovary and ovarian carcinoma
  1. D. Ripley,
  2. R. Tunuguntla,
  3. L. Susi and
  4. N. Chegini
  1. Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida
  1. Address correspondence and reprint requests to: Dr Nasser Chegini, PhD, Department of Obstetrics and Gynecology, University of Florida, Box 100294, Gainesville, FL 32610, USA. Email: cheginin{at}


The objective of this study was to determine the spatial expression of matrix metalloproteinases (MMPs) and their physiologic inhibitors, the tissue inhibitor of MMP (TIMP)-3 and TIMP-4, in ovarian carcinoma compared to normal ovaries. Immunohistochemistry was carried out in this study. Tissue sections prepared from normal ovarian tissues from throughout the menstrual cycle (N = 20) and ovarian carcinomas (N = 45) characterized as stage I (N = 5), stage III/IV (N = 40) were immunostained using polyclonal antibodies to the latent and the active form of MMP-26, TIMP-3, and a monoclonal antibody to TIMP-4. Immunoreactive MMP-26, TIMP-3, and TIMP-4 were detected in all the ovarian cell types in normal and tumor tissues. In normal ovarian tissues, theca externa and luteal cells immunostained with high intensity for MMP-26 and TIMPs while theca/granulosa cell staining intensity increased as lutenization progressed. There was low immunostaining of the ovarian stromal and surface epithelial cells for MMP-26, with moderate staining for TIMPs. In the carcinoma specimens, cancer cells and vascular endothelial cells displayed the highest staining intensity compared to adjacent nontumor areas. The immunostaining intensity of MMP-26 and TIMP-3 increased with stage of tumor with the invading tumor cells displaying the strongest immunostaining. MMP-26, TIMP-3, and TIMP-4 are expressed in normal ovarian as well as ovarian tumors with elevated expression in the invasive tumor cells suggesting a potential role for MMP-26 in normal ovary and ovarian cancer biologic function.

  • cancer
  • menstrual cycle
  • MMP
  • ovary
  • TIMP

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  • This work was presented in part at the 49th Annual Meeting of the Society for Gynecological Investigation, Los Angeles, CA, March 20–23, 2002.

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