Immunophenotype of ovarian cancer as predictor of clinical outcome: evaluation at primary surgery and second-look procedure

Gynecol Oncol. 1998 Sep;70(3):378-85. doi: 10.1006/gyno.1998.5094.

Abstract

Objective: This study was undertaken to evaluate whether immunophenotyping of advanced epithelial ovarian cancer could predict response to initial chemotherapy and whether tumor immunophenotype changed after chemotherapy.

Study design: Fifty-four patients with stage III and IV ovarian cancer, treated at the University of Washington Medical Center, had pathology specimens evaluated. A subset of 23 patients also had specimens from a secondary surgery evaluated. Using immunocytochemistry, tumors were immunostained for overexpression of c-erb-B-2, epidermal growth factor receptor (EGFR), p53, and expression of the Ki67-defined antigen (a marker of cellular proliferation), tumor necrosis factor alpha (TNFalpha), estrogen receptor (ER), progesterone receptor (PR), and P-glycoprotein (P170, a marker of multidrug resistance). Twenty-four patients had a good response to chemotherapy (defined as a negative, or microscopically positive second look), and 30 had a poor response (defined as grossly positive second look or progressive disease).

Results: Comparison of tumor markers from the initial and the secondary surgeries revealed that the only significant change was in the Ki67-defined cell proliferation rate, which showed a marked reduction in those with a good response to chemotherapy (P = 0.002). Comparison of tumor markers at initial surgery between good and poor responders revealed a correlation with p53 expression. Good responders were less likely to have p53 overexpression compared to poor responders, and this result approached significance (P = 0.058). Comparison of tumor markers at secondary surgery revealed a significant reduction in Ki67-defined cell proliferation rate in good responders compared to poor responders (P = 0.01). No significant differences were found between good and poor responders for the other tumor markers evaluated.

Conclusions: The only tumor markers to predict for response to chemotherapy were p53 at initial surgery (P = 0.058) and Ki67 indices at secondary surgery (P = 0.001). Expression of steroid hormone receptors, TNFalpha, and P-glycoprotein and overexpression of c-erb-B-2 or EGFR are not associated with chemoresistance.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Carcinoma / drug therapy*
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunophenotyping
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Predictive Value of Tests
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Reoperation
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • ErbB Receptors
  • Receptor, ErbB-2