Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer

Int J Cancer. 2002 Jun 1;99(4):579-82. doi: 10.1002/ijc.10331.

Abstract

To define the involvement of p16/CDKN2 and p15/MTS2 tumor-suppressor genes for response to chemotherapy in primary epithelial ovarian cancer, we analyzed alterations of the gene in 45 patients who were treated with primary cytoreductive surgery followed by 6 courses of cis-diamminedichloroplatinum (II) (cisplatin)-based combination chemotherapy. Homozygous deletion of p16/CDKN2 and p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to the chemotherapy was confirmed by finding at second surgery after the chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The abundance of gene deletion in nonresponders (56%) was significantly higher (p = 0.0463) when compared to that in responders (18%). Moreover, the deletion of genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a potential indicator for poor chemotherapy response and adverse prognosis in ovarian cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cell Cycle Proteins / genetics*
  • Cisplatin / therapeutic use
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Gene Deletion
  • Genes, p16*
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics*
  • Polymerase Chain Reaction
  • Prognosis
  • Time Factors
  • Treatment Outcome
  • Tumor Suppressor Proteins*

Substances

  • CDKN2B protein, human
  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor p15
  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Proteins
  • Cisplatin