Inactivation of p16/CDKN2 and p15/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer.
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.
Kudoh
Kazuya
K
Department of Obstetrics and Gynecology, Self Defense Force Sendai Hospital, Miyagi 983-8580, Japan. k2-kudoh@xa2.so-net.ne.jp
Ichikawa
Yoshihito
Y
Yoshida
Sadao
S
Hirai
Misako
M
Kikuchi
Yoshihiro
Y
Nagata
Ichiro
I
Miwa
Masanao
M
Uchida
Kazuhiko
K
D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D019942:Genes, p16; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins; D002945:Cisplatin