Epitope recognition by anti-cathepsin D autoantibodies in endometrial cancer patients

Gynecol Oncol. 2001 May;81(2):138-43. doi: 10.1006/gyno.2001.6120.


Objective: This study analyzed a model for the identification of specific epitopes recognized by autologous tumor-reactive humoral responses of endometrial cancer patients as potential markers for the monitoring of cancer.

Methods: The presence of circulating pro- and mature forms of cathepsin D and antibodies reactive with this enzyme were identified by Western immunoblot and quantitated by an enzyme immunoassay. Specific immunoreactivities with 34- and 52-kDa cathepsin D forms were analyzed by Western immunoblot using sera from endometrial cancer patients (n = 40) and normal volunteers (n = 15). Subsequently, reactivities with specific cathepsin D epitopes were defined by a peptide-specific ELISA.

Results: Circulating pro-forms of cathepsin D were detected in 31 of 40 endometrial cancer patients tested and none of the control volunteers. Circulating IgG reactive with cathepsin D could be demonstrated in 29/31 patients with circulating procathepsin D, while an anti-cathepsin D response was not detectable in normal controls. This response appeared to be directed against the pro-peptide portion of cathepsin D. Using a peptide-specific ELISA, the frequencies of antibody production against specific epitopes within the pro-peptide were defined.

Conclusion: There is a demonstrable tumor-reactive immune response elicited in endometrial cancer patients, directed against specific antigenic epitopes, some of which are conserved among these patients. Since these proteins are recognized as non-self, due at least in part to posttranslational processing errors, defining these epitopes will be useful as a means of diagnosis, assessment of therapeutic success, and, ultimately, identification of immunotherapeutic targets.

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Neoplasm / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Cathepsin D / blood
  • Cathepsin D / immunology*
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / immunology*
  • Enzyme Precursors / blood
  • Enzyme Precursors / immunology
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / immunology*
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Molecular Sequence Data


  • Antibodies, Neoplasm
  • Autoantibodies
  • Enzyme Precursors
  • Epitopes
  • Immunoglobulin G
  • procathepsin D
  • Cathepsin D