Influence of chemotherapy on the expression of p53, HER-2/neu and proliferation markers in ovarian cancer.
OBJECTIVE
Mutated p53 and HER-2/neu play a role in the etiology of ovarian cancer. It is important to know whether the expression of these proteins is affected by platinum-containing chemotherapy.


METHODS
Together with the cell proliferation markers Ki-67 and PCNA, the expression of p53 and HER-2/neu was assessed before and after chemotherapy. Paraffin-embedded tumor sections from 20 patients with ovarian cancer and four patients with benign disorders of the ovaries (controls) were analyzed. The expression of p53 was determined by the antibodies DO-1 and BP53-12. In addition to HER-2/neu and PCNA specific antibodies, MIB-1 was used to detect Ki-67.


RESULTS
The expression of all markers was higher in ovarian cancer patients than in non-malignant controls. MIB-1 showed a significant increase of expression after chemotherapy (P=0.002). HER-2/neu, p53 and PCNA also showed a clear increase after treatment, but this was not statistically significant. HER-2/neu is of prognostic relevance with respect to the response to chemotherapy (P=0.005) and survival (P=0.0002).


CONCLUSIONS
The different markers tested all increase after chemotherapy, but the differences are not statistically significant. Low HER-2/neu expression correlates with good outcome at second look.
Nijman
H W
HW
Department of Obstetrics and Gynaecology, Vrije Universiteit Amsterdam, Academic Hospital, The Netherlands.
Kenemans
P
P
Poort-Keesom
R J
RJ
Verstraeten
R A
RA
Mensdorff-Pouilly
S
S
Verheijen
R H
RH
Melief
C J
CJ
Hilgers
J
J
Meijer
C J
CJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D016190:Carboplatin / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000096:biosynthesis; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D016190:Carboplatin; D002945:Cisplatin; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53