The prognostic value of proliferation indices: a study with in vivo bromodeoxyuridine and Ki-67

Proliferation indices are intended to help patients and clinicians make tre atment decisions. We have previously demonstrated that a proliferation inde x based on in vivo labeling of S-phase cells with bromodeoxyuridine (BrdUrd ) correlates with Ki-67 labeling index (LI). We now compare the prognostic value of these indices. With written consent, we gave 129 women with biopsy confirmed breast cancer 200 mg/M-2 BrdUrd during 30 min immediately preceding surgery. We used IU- 4 anti BrdUrd antibody to count the immunohistochemical labeling index (LI) of DNA-incorporated BrdUrd in 2,000 cells and MIB-1 to count Ki-67 (118 ca ses). Patients received standard surgical and adjuvant treatment. No patien ts were lost to follow-up and patients were followed a minimum of 2 (median 5.1) years. We compared survival and recurrence in tumors with high vs low labeling indices. We found that women in the low BrdUrd LI group had bette r disease free survival (92% vs 67% 5-yr DFS p = 0.001) and overall surviva l (94% vs 70% 5-yr OS, p = 0.0001) than those with a high LI. In comparison , a low Ki-67 index predicted better OS (87% vs 80% 5-yr OS, p = 0.020) and a trend for better DFS (84% vs 72% DFS p = 0.055). The apparent superiorit y of BrdUrd LI over Ki-67 LI is likely due to chance (p = 0.18). In multiva riate survival analyses we found that BrdUrd LI proliferative index signifi cantly improves prediction of DFS or OS even when node status, age or tumor size is in the model. We conclude that markers of proliferation are useful adjuncts in predicting patient prognosis.