CD117 expression is a predictive marker for poor prognosis in patients with non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) accounts for >85% of incidences of lung cancer, for which the predicted 5-year survival rates are low and recurrence rates remain high. Although it has been reported that the patients with SCLC cells that possess the cluster of differentiation (CD) 117 marker exhibited poor prognosis and poor response to chemotherapy, no studies concerning the association of CD117 expression with prognosis of the patients with NSCLC have been reported. An in vitro study reportedly revealed that CD117-positive cell populations in NSCLC cell lines exhibited cancer stem cell (CSC) phenotypes including self-renewal and chemoresistance. Therefore, the present study hypothesized that if CD117-positive cells are CSC-like cells, CD117 positivity may be associated with the prognosis of patients with NSCLC. To confirm this hypothesis, the association between CD117 expression in patients with NSCLC and clinicopathological characteristics was investigated. CD177 expression was examined by immunohistochemistry in 99 patients with NSCLC who underwent curative surgical resection. Tumor samples in the present study included 73 samples of adenocarcinoma and 26 of squamous carcinoma. The associations of CD177 expression with clinicopathological features and prognosis were examined. The lymph node metastasis and rates of recurrence were significantly associated with overall survival rates through multivariate analysis (P<0.001 and P<0.001), respectively. A Kaplan-Meier analysis for relapse-free survival and the log-rank test revealed that the patients with CD117-positive cell populations exhibited shorter relapse-free survival rates compared with patients whose cells were CD117-negative (P=0.014). The multivariate analysis demonstrated that venous invasion, pathological stage, and CD117 expression were independent prognostic parameters for relapse-free survival in patients with NSCLC (P=0.001, P=0.001 and P=0.002), respectively. In conclusion, these data suggest that CD117 expression in NSCLC may serve as a useful marker for predicting the prognosis of patients with NSCLC.

Keywords: CD117; immunohistochemistry; non-small cell lung cancer; prognostic marker; relapse-free survival.

Figure 1.

Immunohistochemical staining of CD117 expressions in patients with non-small cell lung cancer. Representative images of CD117 expression in FFPE non-small cell lung cancer tissues. Positive expression of CD117 in FFPE lung (A) adenocarcinoma tissues and FFPE lung (B) squamous cell carcinoma tissues. The expression of CD117 was demonstrated using the avidin-biotin complex staining method. All images were captured using a Nikon Eclipse E800 upright microscope (x400 magnification). FFPE, formalin-fixed paraffin-embedded; CD, cluster of differentiation.

Figure 2.

Kaplan-Meier analysis for overall survival rate in 99 non-small lung cancer cell patients. Patients were classified into negative (82 cases) and positive groups (17 cases) according to the expression of CD117. Data analysis was performed using the log-rank test. CD, cluster of differentiation, gray curve, CD117-negative group; black curve, CD117-positive group.

Figure 3.

Kaplan-Meier analysis for relapse-free survival in 99 non-small lung cancer cell patients. Patients were classified into negative (82 cases) and positive groups (17 cases) according to the expression of CD117. Data analysis was performed using the log-rank test. CD, cluster of differentiation, gray curve, CD117-negative group; black curve, CD117-positive group.