Prognostic value of the copper transporters, CTR1 and CTR2, in patients with ovarian carcinoma receiving platinum-based chemotherapy

Gynecol Oncol. 2011 Aug;122(2):361-5. doi: 10.1016/j.ygyno.2011.04.025. Epub 2011 May 13.

Abstract

Objective: CTR1 and CTR2 are copper transporters that have been associated with platinum sensitivity in several human cancers. We investigated the prognostic significance of CTR1 and CTR2 in women with ovarian carcinoma.

Materials and methods: We evaluated the expression of CTR1 and CTR2 using real-time PCR in 40 women with ovarian carcinoma (IIb=2, IIIb=2, IIIc=30, IV=6). We compared the expression of CTR1 and CTR2 with participants' clinicopathological findings.

Results: We found lower expression of CTR1 and CTR2 mRNA in ovarian cancer cells against normal ovarian tissue with statistically significant differences (p=0.018 and 0.011, respectively). High CTR1 expression was a prognostic factor for improved survival after adjusting for age, tumor grade, stage, residual tumor, and CTR2 mRNA expression (HR, 0.35; 95% CI, 0.15-0.84). However, CTR2 expression did not exhibit any prognostic significance. Of the 20 women with elevated CTR1 expression, 17 (85%) were sensitive to platinum-based chemotherapy. Of the 7 women with low CTR1 expression and high CTR2 expression, 6 (85.7%) were resistant to platinum-based chemotherapy and had the shortest progression-free survival of all women in our study sample.

Conclusion: In our sample of 40 women with ovarian carcinoma, high CTR1 expression was significantly associated with sensitivity to platinum-based chemotherapy and longer progression-free survival. Conversely, low CTR1 expression and high CTR2 expression were significantly associated with resistance to platinum-based chemotherapy and the shortest survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / therapeutic use*
  • Cation Transport Proteins / analysis
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / physiology*
  • Copper Transporter 1
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Polymerase Chain Reaction
  • Prognosis
  • RNA, Messenger / analysis
  • Retrospective Studies
  • SLC31 Proteins

Substances

  • Cation Transport Proteins
  • Copper Transporter 1
  • RNA, Messenger
  • SLC31 Proteins
  • SLC31A1 protein, human
  • SLC31A2 protein, human
  • Carboplatin