Clinical relevance of CD44 surface expression in advanced stage serous epithelial ovarian cancer: a prospective study

J Cancer Res Clin Oncol. 2016 May;142(5):949-58. doi: 10.1007/s00432-016-2116-5. Epub 2016 Jan 13.

Abstract

Purpose: Cluster of differentiation (CD) 44 is a cell surface receptor that correlates with the development of drug resistance in epithelial ovarian cancer (EOC). Here, we prospectively investigated the clinical impact of CD44 expression on the development of chemoresistance, and on disease-free and overall survival in EOC.

Methods: This study included patients with primary serous EOC that was at International Federation of Gynecology and Obstetrics stages IIIB-IVA and tumors that were CD44 positive and negative in a 1:1 ratio. All patients underwent primary surgical cytoreduction, followed by six cycles of combined paclitaxel and carboplatin chemotherapy every 3 weeks. The treatment was considered complete after the chemotherapy had finished. All patients were followed up for 24 months after completing their chemotherapy.

Results: Of the 96 patients with serous EOC at stages IIIB-IVA, 51 % of the tumors were negative for the expression of CD44 and 49 % showed variable CD44 expression. Patients who had CD44-positive tumors had statistically significant shorter disease-free (p ≤ 0.001) and overall survival (p ≤ 0.001) intervals compared with patients with CD44-negative tumors. The hazard ratio for death was 6.8 (95 % confidence interval 2.4-19.2, p ≤ 0.001) among the patients with CD44-positive tumors. A multivariate analysis showed that carboplatin-resistant or carboplatin-refractory EOC was the only independent predictive factor for death.

Conclusions: CD44 expression contributes to the development of carboplatin resistance in advanced serous EOC, and it may contribute to worse prognoses for patients, but it is neither an independent predictor of survival nor of recurrence.

Keywords: Cluster of differentiation 44; Epithelial ovarian cancer; Platinum resistance.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Carboplatin / therapeutic use
  • Carcinoma, Ovarian Epithelial
  • Cystadenocarcinoma, Serous / drug therapy
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / mortality
  • Cystadenocarcinoma, Serous / pathology*
  • Drug Resistance, Neoplasm*
  • Female
  • Follow-Up Studies
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Immunoenzyme Techniques
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Recurrence, Local / pathology*
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / drug therapy
  • Neoplasms, Glandular and Epithelial / metabolism
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • Prospective Studies
  • Survival Rate

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CD44 protein, human
  • Hyaluronan Receptors
  • Carboplatin