Clinical significance of Ki-67 and p53 expression in curatively resected non-small cell lung cancer

Abstract

The aim of this study is to explore the association of Ki-67 and p53 expression with prognosis in non-small cell lung cancer (NSCLC) patients who underwent curative resection. We retrospectively identified 116 consecutive patients with stages I-III NSCLC who underwent curative resection at a single center from January 2007 to December 2012. Ki-67 and p53 expression was assessed by immunohistochemistry. Data on clinicopathologic features and survival were collected retrospectively. Ki-67 expression in 109 samples and p53 expression in 115 patients were analyzed. According to the results, 108 patients (99 %) showed at least some expression of Ki-67. The median Ki-67 expression level was 30 %. Positive p53 expression was observed in 91 (79 %) patients. Higher Ki-67 expression (>40 %) was significantly more frequent in male (26 vs. 4 % in female, p=0.002), ever-smoker (31 vs. 10 % in never-smoker, p=0.024), and non-adenocarcinoma (30 vs. 11 % of adenocarcinoma, p=0.012) patients. In univariable analysis, median disease-free survival (DFS) was shorter with higher Ki-67 expression (16.1 vs. 61.9 months in those with lower Ki-67 expression, p=0.005), and p53 expression did not show an association with DFS. Among 42 patients with stage I NSCLC who did not receive adjuvant chemotherapy, DFS was significantly worse in patients with higher Ki-67 expression (2-year DFS rate 57 vs. 88 %, p=0.018). In a Cox regression model, higher Ki-67 expression (>40 %) was a significant independent prognostic factor associated with poorer DFS (HR 2.9, 95 % CI 1.3-6.2) along with TNM stage and age. Higher Ki-67 expression (>40 %) showed an independent association with shorter DFS in NSCLC patients who underwent curative resection.

Correlation between radiomic features based on contrast‐enhanced computed tomography images and Ki‐67 proliferation index in lung cancer: A preliminary study

“…The difference in Ki‐67 cutoff value between our study and others could cause statistical bias. In our study, high Ki‐67 expression showed an association with poor prognostic clinical factors, including male gender and smoking history, consistent with the results of previous research . Despite this concordance, our results require verification by further study.…”

“…Determining a cutoff value is often based on the median value. In accordance with a previous study and based on our data, we used a cutoff value of 40% for Ki‐67 expression . The difference in Ki‐67 cutoff value between our study and others could cause statistical bias.…”

“…The Ki‐67 indices were calculated in the three regions and averaged. Low Ki‐67 expression was defined as ≤ 40% positive staining and high Ki‐67 expression as > 40% positive staining according to a previous study …”

“…Ki‐67, a nuclear protein, is expressed during the active phases of the cell cycle, except the G0 stage, and the Ki‐67 proliferation index (PI) has widely been used as a marker of cell proliferation. Previous studies have shown that a high Ki‐67 PI has a negative impact on disease‐free survival, relapse‐free survival, and overall survival in non‐small cell lung cancer . Moreover, the most recent World Health Organization (WHO) classification has adopted the Ki‐67 PI for the diagnosis of small cell lung cancer (SCLC) and a higher Ki‐67 PI may represent a predictive factor for increased tumor radiosensitivity in SCLC .…”

Correlation of diffusion MRI with the Ki-67 index in non-small cell lung cancer

“…[13][14][15][16][17][18][19] The Ki-67 index has also been used routinely in the evaluation of lung tumours and has been shown to be an important prognostic factor for lung cancer. 3,6,[20][21][22][23][24][25][26][27] Although a few studies have evaluated the association of ADC with Ki-67 index in lung tumours 3,6 , no study has previously investigated differences in the ADC/Ki 67 correlation in different tumour subtypes.…”