c-myc and chromosome 8 centromere studies of ovarian cancer by interphase FISH.
Forty tumor specimens from patients with ovarian cancer were studied for amplification of the c-myc oncogene relative to chromosome 8 centromere number using dual-color FISH. Interphase cytogenetic analysis showed amplification of the c-myc oncogene in 40% (16/40) of tumors using the standard oncogene:centromere ratio method of analysis. Eleven of these showed moderate amplification of c-myc, and 5 samples showed high amplification. Eight of the sixteen (50%) amplified tumors were polysomic centromere 8 as were 14 of the 24 (58%) non-amplified tumors. In previously reported work with these samples, the oncogene HER-2/neu, the chromosome 17 centromere, and the tumor suppressor gene p53 had been studied. When using the standard oncogene:centromere ratio criteria, 5 samples had amplification of both the c-myc and the HER-2/neu oncogenes, 5 samples had HER-2/neu amplification but not c-myc, 11 samples had c-myc amplification but not HER-2/neu, and 19 samples had neither oncogene amplified. The p53 gene was found to be deleted in 22.5% (9/40) of samples. The loss of the p53 gene did not appear to have any clinical correlation. The presence of an extra centromere 8 also did not appear to have any clinical correlation. The Kaplan-Meier survival curve for those patients who have c-myc amplification, while not statistically significant, appears to show a trend toward poorer survival. The survival curve for patients whose tumors have HER-2/neu amplification shows no clinical significance. It is of great interest, however, that the Kaplan-Meier plot of survival for patients whose tumors have amplification of both c-myc and HER-2/neu shows a significant difference (P = 0.047). The median survival times of the doubly amplified patient group and the non-doubly amplified groups were 12 and 43 months, respectively. This is the first study of the oncogene c-myc using FISH. The results suggest that the amplification of c-myc may indicate a poorer patient survival and that the amplification of both c-myc and HER-2/neu in combination may be a better prognostic indicator of poor patient survival.
Wang
Z R
ZR
Department of Obstetrics and Gynecology, University of South Carolina School of Medicine.
Liu
W
W
Smith
S T
ST
Parrish
R S
RS
Young
S R
SR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002503:Centromere / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007399:Interphase / Q000235:genetics; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D015996:Survival Rate
D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases