Changes in Ki-67 labeling indices during neoadjuvant chemotherapy for advanced ovarian cancer are associated with survival.
OBJECTIVE
To evaluate changes in Ki-67 expression during neoadjuvant chemotherapy (NACT) in advanced ovarian cancer.


METHODS
Patients with International Federation of Gynecology and Obstetrics stage IIIC or IV and large-volume ascites were treated with NACT within a phase 2 trial. The expression of Ki-67 was evaluated by immunohistochemistry on paraffin-embedded tissue samples and classified by percentage of stained cells. Survival curves were plotted using the Kaplan-Meier method.


RESULTS
Comparison of 40 individual paired results from pretreatment and posttreatment samples revealed a median difference of -0.11 in the Ki-67 index (95% confidence interval, -0.20 to -0.01; P = 0.005, signed rank test). Univariate analysis identified a high Ki-67 index as well as an increasing Ki-67 index after NACT as significant prognostic markers for progression-free survival (P = 0.004 and P = 0.001; log-rank test). Six of 12 patients with an increased Ki-67 index after NACT developed recurrence within 6 months after therapy.


CONCLUSIONS
Changes of the Ki-67 index during NACT are associated with progression-free survival. If confirmed in prospective trials, an increasing Ki-67 index during preoperative treatment may serve as an indicator for resistance to chemotherapy.
Pölcher
Martin
M
Department of Gynecology and Obstetrics, Center for Integrated Oncology, University of Bonn, Medical Center, Bonn, Germany. martin.poelcher@ukb.uni-bonn.de
Friedrichs
Nicolaus
N
Rudlowski
Christian
C
Fimmers
Rolf
R
Keyver-Paik
Mignon-Denise
MD
Kübler
Kirsten
K
Sauerwald
Axel
A
Büttner
Reinhard
R
Kuhn
Walther
W
Braun
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D049109:Cell Proliferation; D017322:Clinical Trials, Phase II as Topic; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000077143:Docetaxel; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin