Evaluation of Tumor Cell Proliferation by Ki-67 Expression and Mitotic Count in Lymph Node Metastases from Breast Cancer

• Published in: PloS one 2016-03, Vol.11 (3), p.e0150979
• Main Authors: Aziz, Sura, Wik, Elisabeth, Knutsvik, Gøril, Klingen, Tor Audun, Chen, Ying, Davidsen, Benedicte, Aas, Hans, Aas, Turid, Akslen, Lars A
• Format: Article
• Language: English
• Subjects: Aged; Analysis; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor; Biopsy; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Cancer metastasis; Cancer screening; Care and treatment; Cell growth; Cell Proliferation; Clinical medicine; Complications and side effects; Female; Gene Expression; Genetic aspects; Health aspects; Health risks; Hospitals; Humans; Identification and classification; Immunohistochemistry; Ki-67 Antigen - genetics; Ki-67 Antigen - metabolism; Lymph nodes; Lymphatic Metastasis; Lymphatic system; Mammography; Markers; Medical examination; Medical prognosis; Medical screening; Medicine; Medicine and Health Sciences; Metastases; Metastasis; Middle Aged; Mitotic Index; Multivariate analysis; Neoplasm Grading; Pathology; Patient Outcome Assessment; Physical Sciences; Prognosis; Proportional Hazards Models; Research and Analysis Methods; Studies; Surgery; Survival; Tumor Burden; Tumor cells; Tumor markers; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150979

Few studies have addressed the risk of recurrence by assessing proliferation markers in lymph node metastasis from breast cancer. Here, we aimed to examine Ki-67 expression and mitotic count in lymph nodes in comparison with primary tumors. A cohort of node positive breast cancer (n = 168) was studied as a part of the prospective Norwegian Breast Cancer Screening Program (1996-2009). The percentage of Ki-67 positivity was counted per 500 tumor cells in hot-spot areas (x630). Mitotic count was conducted in the most cellular and mitotic active areas in 10 high power fields (x400). Our results showed that Ki-67 and mitotic count were significantly correlated between primary tumor and lymph nodes (Spearman`s correlation 0. 56 and 0.46, respectively) and were associated with most of the histologic features of the primary tumor. Univariate survival analysis (log-rank test) showed that high Ki-67 and mitotic count in the primary tumor and lymph node metastasis significantly predicted risk of recurrence. In multivariate analysis, mitotic count in the lymph node metastasis was an independent predictor of tumor recurrence. In conclusion, proliferation markers in lymph node metastases significantly predicted disease free survival in node positive breast cancer.