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Risk Factors Associated with Discordant Ki-67 Levels between Preoperative Biopsy and Postoperative Surgical Specimens in Breast Cancers

 Hyung Sun Kim  ;  Seho Park  ;  Ja Seung Koo  ;  Sanghwa Kim  ;  Jee Ye Kim  ;  Sanggeun Nam  ;  Hyung Seok Park  ;  Seung Il Kim  ;  Byeong-Woo Park 
 PLOS ONE, Vol.11(3) : e0151054, 2016 
Journal Title
Issue Date
Adult ; Biomarkers, Tumor* ; Biopsy ; Breast Neoplasms/metabolism* ; Breast Neoplasms/pathology* ; Breast Neoplasms/surgery ; Female ; Humans ; Immunohistochemistry ; Ki-67 Antigen/genetics ; Ki-67 Antigen/metabolism* ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Postoperative Period ; Preoperative Period ; Receptor, ErbB-2/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Progesterone/metabolism ; Risk Factors ; Tumor Burden
PURPOSE: The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values.
PATIENTS AND METHODS: Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67-1.5 × interquartile range (IQR)] or (upper quartile + 1.5 × IQR) and were evaluated according to clinicopathological parameters by logistic regression analysis.
RESULTS: The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15) and 10 (IQR, 25), respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676). Of 310 patients, 44 (14.2%) showed outliers of ΔKi-67 (range, ≤-20 or ≥28). A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR) expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9%) patients and a significant proportion of patients with discordant cases had ≥1 risk factor.
CONCLUSION: Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67 values should be cautious considering types of specimens and clinicopathological risk factors.
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1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Koo, Ja Seung(구자승) ORCID logo https://orcid.org/0000-0003-4546-4709
Kim, Seung Il(김승일)
Kim, Hyung Sun(김형선) ORCID logo https://orcid.org/0000-0002-9002-3569
Nam, Sanggeun(남상근)
Park, Byeong Woo(박병우) ORCID logo https://orcid.org/0000-0003-1353-2607
Park, Se Ho(박세호) ORCID logo https://orcid.org/0000-0001-8089-2755
Park, Hyung Seok(박형석) ORCID logo https://orcid.org/0000-0001-5322-6036
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