Amplicon profiling reveals cytoplasmic overexpression of MUC1 protein as an indicator of resistance to platinum-based chemotherapy in patients with ovarian cancer.
Chromosomal gains of 1q21-q22 and 13q12-q14 were closely related with the chemoresistance of patients with ovarian cancer in our previous CGH (comparative genomic hybridization) study. We conducted the present study to determine the amplified genes on chromosome 1q. Comparisons of relative copy numbers of clinically platinum-sensitive ovarian tumors (CR-group, n=14) and platinum-resistant tumors (PD-group, n=14) were carried out using real-time PCR from ten different gene loci on chromosome 1q. Increased copy numbers were frequently observed in PD-group tumors, especially in the region between WI-8123 and MUC1. Relative copy number of MUC1 over 1.5 was observed in 13 (92%) of 14 PD-group tumors and 3 (21%) of 14 CR-group tumors (p<0.05). Moreover, cytoplasmic expressions of MUC1 protein were significantly higher in PD-group than those in CR-group (p<0.01). We concluded that the cytoplasmic overexpression of MUC1 might be an indicator of resistance to platinum-based chemotherapy and a prognostic marker in ovarian cancer.
Takano
Masashi
M
Department of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan. mastkn@me.ndmc.ac.jp
Fujii
Kazuyuki
K
Kita
Tsunekazu
T
Kikuchi
Yoshihiro
Y
Uchida
Kazuhiko
K
D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D003593:Cytoplasm / Q000378:metabolism*; D017931:DNA Primers; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics*; D017671:Platinum Compounds / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000970:Antineoplastic Agents; D017931:DNA Primers; C116055:MUC1 tandem repeat peptide; D018396:Mucin-1; D010446:Peptide Fragments; D017671:Platinum Compounds