Abstract 5285: Ki-67 expression and mitotic count in lymph node metastasis and their association with clinico-pathologic features and survival in aggressive breast carcinoma
Authors: Aziz Sura M. , Wik Elisabeth , Knutsvik Gøril , Collett Karin , Akslen Lars Andreas 
Published: August 2015

Abstract
Background: Proliferation markers in breast cancer are prognostic and might be predictive for therapy response. However, their prognostic and predictive power in lymph node metastasis is not well established. The aim of our study was to examine the prognostic role of these markers in lymph node metastasis in comparison with the matched primary tumor.
Study design: A retrospective series of node-positive breast cancers (n = 111) was used, as a part of the Norwegian Breast Cancer Screening Program (1996-2003). Sections from the largest node with metastasis (&gt; 2mm) were used. The percentage of Ki-67 staining per 500 tumor cells was counted in hot-spot areas. The mitotic count was determined in the most active areas, using 10 consecutive high power fields (x400), and the number of mitotic figures per mm2 was calculated. Assessment of Ki-67 expression and mitotic count was performed on corresponding primary tumors.
Results: The two proliferation markers were highly correlated between metastasis and their matched primary tumors (r = 0.58, 0.46 for Ki-67 and mitotic count, respectively). Ki-67% in metastasis was slightly but significantly lower than in their primary tumors (median = 15.8 vs 17.2, P = 0.013). In contrast, mitotic count in metastasis was slightly but significantly higher than in their primary lesions (median = 1.4 vs 1.2, P = 0.02). The proliferation markers in metastasis showed a significant association with known unfavorable prognostic features in the primary tumor, including tumor diameter, histologic grade, hormone receptor status, HER2 status and molecular subtype.
A subgroup of concordant cases with high proliferation (in matched metastasis and primary tumors) was significantly associated with large tumor diameter (&gt;2 cm), negative hormone receptors, positivity for Her2 status, as well as the triple negative molecular subtype.
Survival analysis (Kaplan-Meier method, log-rank test) for Ki-67 and mitosis alone in lymph node metastasis showed no statistical significant association with breast cancer specific survival. However, this association was significant when comparing the subgroup with concordant high proliferation to all other subgroups with different proliferation patterns (P = 0.01, 0.01 for Ki-67 and mitosis, respectively). In multivariate analysis, the subgroup with concordant high proliferation for Ki67, and tumor diameter, were the only prognostic factors of independent importance.
Conclusion: Proliferation markers in lymph node metastasis are strongly associated with the most unfavorable features of the primary tumors. Combined high proliferation in metastases and primary lesions is associated with reduced breast cancer specific survival. In multivariate analysis, combined high Ki67 was prognostic together with tumor diameter.
Citation Format: Sura M. Aziz, Elisabeth Wik, Gøril Knutsvik, Karin Collett, Lars Andreas Akslen. Ki-67 expression and mitotic count in lymph node metastasis and their association with clinico-pathologic features and survival in aggressive breast carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5285. doi:10.1158/1538-7445.AM2015-5285