Assessment of tumor cell repopulation after chemotherapy for advanced ovarian cancer: Pilot study

Background: Repopulation of clonogenic tumor cells appears to increase during fractionated radiation treatment and is recognized as an important factor affecting local control. Given the longer intervals between cycles and longer total duration of treatment, the impact of repopulation is likely to be greater after chemotherapy. Methods: We assessed tumor cell repopulation with the proliferative marker Ki-67 in 21 patients with ovarian carcinoma who received initial chemotherapy. Paraffin slides were evaluated from the diagnostic biopsy and from tumor obtained at debulking surgery after chemotherapy. Immunohistochemistry using the MIB-1 antibody was performed on the paired samples and analyzed with a digital imaging device linked to a color camera mounted on a transmitted-light microscope. The ratio of Ki-67 positive to all nuclei was used as a proliferative index and compared for pre- and postchemotherapy specimens. Results: All patients received platinum-based chemotherapy and most showed a response to treatment. The median duration between last chemotherapy and debulking surgery was 33 days (range, 22-50 days). Four (19%) of 21 patients showed an increased proliferative index after chemotherapy, and the remainder showed a decrease (n = 12) or no significant change (n = 5). Conclusions: Our results did not suggest an increase in proliferation of tumor cells after this type of chemotherapy in the majority of patients with ovarian cancer.