Proliferation Markers PHH3, Ki67 and Mitotic Count All Show Significant Associations with Features of Aggressive Breast Carcinomas and Reduced Survival
Goril Knutsvik, Ingunn M Stefansson, Karin Collett, Lars A Akslen. University of Bergen, Bergen, Norway; Haukeland University Hospital, Bergen, Norway
Background: Determination of proliferation in breast carcinomas is highly prognostic and may also predict response to chemotherapy. However, there is no consensus on issues such as counting area or cut-off values. Our aim was to evaluate Ki67 counts in different tumor areas as compared with the novel mitosis marker phosphohistone H3 (PHH3) and standard mitotic count. Furthermore, we aimed to assess the prognostic value of these proliferation markers.
Design: We examined a retrospective, population-based series (n = 556) as part of the Norwegian Breast Cancer Screening Program, including all women (50-69 years) diagnosed with breast cancer in one county of Norway between 1996-2003. The percentage of Ki67 positive nuclei among 500 tumor cells was evaluated for both hot-spots (HS; highest proliferation) and cold-spots (CS; lowest proliferation) on full sections. For standard mitotic count and PHH3, mitotic figures were counted in 10 consecutive high power fields (HPF) in the most active area, and the number of mitoses per mm2 was calculated.
Results: The 3 proliferation markers were highly correlated. The upper quartiles for Ki67-HS, Ki67-CS, PHH3 and mitotic count consistently showed the strongest associations with known unfavorable tumor features, including larger tumor diameter, high histologic grade, and negative estrogen receptor (ER) and progesterone receptor (PR) status. High proliferation was significantly associated with interval cancers as compared with screen-detected cases. In a subset of cases (n = 190), follow-up data were available (information is currently collected on all cases). Univariate survival analysis of this subgroup showed comparable prognostic strength of Ki67-HS, PHH3 count and mitotic count. In multivariate analysis, mitotic count was the strongest prognostic factor among these.
Conclusions: By upper quartile, Ki67-HS, PHH3 and mitotic count all showed strong associations with various unfavorable tumor features. In multivariate survival analysis of a subset of patients, mitotic count was the strongest proliferation marker.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 17, Wednesday Afternoon