Expression of the c-myc gene as a predictor of chemotherapy response and a prognostic factor in patients with ovarian cancer.
The present study was conducted to determine whether and how expression of the c-myc gene is related to the response to chemotherapy in patients with epithelial ovarian cancer. This study includes 101 consecutive patients with stage Ic to IV epithelial ovarian cancer who underwent primary surgery followed by platinum-based chemotherapy. Immunohistochemical studies were performed to detect Ki-67 and ARF proteins. Apoptotic cells were identified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling method. Mutation of the p53 gene was screened by polymerase chain reaction (PCR)-single strand conformation polymorphism analysis and confirmed by direct sequencing. mRNA expression of c-myc was determined by means of reverse transcription-PCR. Apoptotic index (AI) and ARF labeling index (LI) were significantly increased and Ki-67 LI was decreased after chemotherapy in patients from whom specimens could be obtained before and after chemotherapy. AI, ARF LI, and Ki-67 LI were not related to p53 gene status. A significant correlation between expression of c-myc and ARF LI was observed. Of 38 patients with measurable lesion, 23 (60.5%) responded to chemotherapy and 15 (39.5%) did not. Tumors with the wild-type p53 gene responded significantly better to chemotherapy than did tumors with the mutation. Responders showed a higher expression of c-myc than nonresponders (468 +/- 76 vs. 187 +/- 68). The receiver operating characteristic (ROC) curve according to chemoresponse demonstrated that the cut-off value of c-myc expression was 200. Patients with c-myc expression of more than 200 had a better 5-year survival rate (69.8% vs. 43.5%; 101 patients). Multivariate analysis revealed that c-myc expression was an independent prognostic factor. Our results suggest that the expression of c-myc gene is related to chemoresponse and might be a useful prognostic factor in patients with epithelial ovarian cancer.
Iba
Takahiro
T
Department of Obstetrics and Gynecology, Tottori University School of Medicine, Yonago 683-8504, Japan.
Kigawa
Junzo
J
Kanamori
Yasunobu
Y
Itamochi
Hiroaki
H
Oishi
Tetsuro
T
Simada
Muneaki
M
Uegaki
Kazunori
K
Naniwa
Jun
J
Terakawa
Naoki
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000601:surgery; D017239:Paclitaxel / Q000008:administration & dosage; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011237:Predictive Value of Tests; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D016019:Survival Analysis; D016896:Treatment Outcome
C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016190:Carboplatin; D017239:Paclitaxel