Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients

Abstract

The aim of the present study was to identify the optimal Ki-67 cut-off value in breast cancer (BC) patients, and investigate the association of Ki-67 expression levels with other prognostic factors. Firstly, a retrospective search was performed to identify patients with stage I–III BC (n=462). A range of Ki-67 index values were then assigned to five groups (<10, 10–14, 15–19, 20–24 and ≥25%). The correlation between the Ki-67 index and other prognostic factors [age, tumor type, histological and nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were investigated in each group. The median Ki-67 value was revealed to be 20% (range, 1–95%). A young age (≤40 years old), tumor type, size and grade, LVI, ER/PR negativity and HER-2 positivity were revealed to be associated with the Ki-67 level. Furthermore, Ki-67 was demonstrated to be negatively correlated with ER/PR expression (P<0.001), but positively correlated with tumor size (P<0.001). The multivariate analysis revealed that a Ki-67 value of ≥15% was associated with the largest number of poor prognostic factors (P=0.036). In addition, a Ki-67 value of ≥15% was identified to be statistically significant in association with certain luminal subtypes. The rate of disease-free survival was higher in patients with luminal A subtype BC (P=0.036). Following the correlation analysis for the Ki-67 index and the other prognostic factors, a Ki-67 value of ≥15% was revealed to be the optimal cut-off level for BC patients.

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

“…39,40 Ki-67 is a nuclear protein that is commonly used for the detection and quantification of proliferating cells. 28 In agreement with the observations by others, 35,50,51 it was found that Ki-67 positively connected with Her-2 overexpression in this study, suggesting that Her-2 overexpression might upregulate the expression of Ki-67.…”

“…12 In agreement with the observation by Kobayashi et al, 61 our finding that p53 positive is connected with the progression of carcinoma to a higher histological grade and Her-2 overexpression in breast cancer patients suggests that p53 positive could be used as a prognostic biomarker for breast cancer 56,[62][63][64] in addition to being used as a diagnostic biomarker. 38 Our findings that Ki-67 positive is connected with the progression of carcinoma to a higher histological grade as well as Her-2 overexpression in breast cancer patients are consistent with the previous observations 5,35,50,61 and increase the reliability of this emerging biomarker 38 as a predictor of breast cancer prognosis outcomes. Our observation that both PR positive and ER positive are connected with a slower histological progress and are negatively connected with Her-2 overexpression in breast cancer supports that PR positive and ER positive are good biomarkers for predicting better prognosis and response to endocrine therapy than patients that lacked these receptors.…”

“…30,31 ER and PR were negatively correlated with Her-2 overexpression. 32,33 The association between Her-2 and Ki-67 in breast cancer patients 5,6,31,34,35 makes Ki-67 an emerging biomarker for breast cancer. 36 This study retrospectively compared 160 cases of Her-2 overexpressing breast cancer patients with 100 cases of Her-2 negative patients in terms of clinicopathological characteristics and the expression of p53 and Ki-67, and further uncovered the connection among Her-2, p53 and Ki-67.…”

Reduction of global 5-hydroxymethylcytosine is a poor prognostic factor in breast cancer patients, especially for an ER/PR-negative subtype

“…Distinct breast cancer molecular subtypes are well associated with specific morphological characteristics and various clinical outcomes [3][4][5]. Previous studies reported that ER status was negatively correlated with Ki-67, suggesting that the high-proliferating breast tumors were observed in patients with ER-negative subtype [46,47]. Depletion of 5hmC has been identified depending on cell proliferation in numerous types of human cancer via passive demethylation [16][17][18][19].…”

Favorable Reproducibility of Ki-67-Labeling Index between Core Needle Biopsy and Surgical Materials in Mammary Carcinoma: Reproducibility Influenced by Hot Spots, a High Ki-67 Labeling Index, and the Total Length of Biopsy Material

“…The optimal cut-off value of the Ki-67-labeling index has been controversial, although there have been a number of reports on it [5] [6] [7] [8]. At the 2015 St. Gallen Consensus Conference, there was no optimal cut point of the Ki-67-labeling index.…”