DNA ploidy and MYC DNA amplification in ovarian carcinomas. Correlation with p53 and bcl-2 expression, proliferative activity and prognosis.
There is increasing evidence that DNA ploidy is a prognostic factor in ovarian carcinomas, but it is uncertain whether MYC DNA amplification is an epiphenomenon of DNA nondiploidy or a distinct biological change with an impact on the clinical course of the disease. To clarify these issues we analysed DNA ploidy by flow and image cytometry and MYC copy number by polymerase chain reaction in archival material from ovarian carcinomas with known follow up. The results were compared with proliferative activity (Ki67 index) and p53 and bcl-2 expression. DNA cytometry revealed nondiploidy in 84 of 144 cases (58.3%). Nondiploidy was statistically significantly correlated with histological tumour type, histological grade, Ki67 index > 10%, FIGO stage, presence of residual tumour after debulking surgery and adverse postoperative outcome. Furthermore, DNA nondiploidy was associated with p53 accumulation. We found that 84.9% of the p53-positive cases were nondiploid. This points to the paramount importance of wild type p53 for the maintenance of genome integrity in this tumour type. MYC DNA amplification was seen in 33.8% (26/77 cases) of ovarian carcinoma. There was no correlation between MYC DNA amplification and histological tumour type, histological grade, FIGO stage, DNA ploidy, proliferative activity or prognosis. However, when p53 and bcl-2 expression was taken into account, a statistically significant correlation between gene alteration or expression patterns and histological tumour type was revealed. The group of mucinous carcinomas demonstrated both MYC DNA amplification and strong bcl-2 expression in 50% and contained the largest fraction of cases without aberration (37.5%). Endometrioid carcinomas were characterized by strong bcl-2 expression in 85%, whereas serous and undifferentiated carcinomas predominantly exhibited p53 alterations, frequently accompanied by bcl-2 overexpression or MYC DNA amplification. Thus, in interaction with other genes MYC DNA amplification may play a role in the determination of the varying differentiation patterns of ovarian carcinomas.
Diebold
J
J
Pathological Institute, Ludwig Maximilians University, München, Germany.
Suchy
B
B
Baretton
G B
GB
Blasenbreu
S
S
Meier
W
W
Schmidt
M
M
Rabes
H
H
Löhrs
U
U
D000368:Aged; D002277:Carcinoma / Q000175:diagnosis* / Q000235:genetics; D004273:DNA, Neoplasm / Q000737:chemistry*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005784:Gene Amplification / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D006801:Humans; D019044:Image Cytometry / Q000379:methods; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics; D011003:Ploidies; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53