Topoisomerase II alpha expression and the benefit of adjuvant chemotherapy for postoperative patients with non-small cell lung cancer

Abstract

Background: Adjuvant chemotherapy has been shown to improve survival rates of postoperative patients with non-small cell lung cancer (NSCLC). Biomarkers could help select an appropriate chemotherapy for NSCLC patients or predict the efficacy of chemotherapy. The objective of this study was to explore the possible prognostic and predictive role of topoisomerase II alpha (TopIIα) expression level in postoperative NSCLC patients who received adjuvant chemotherapy.

Methods: Patients with stage I-III NSCLC, who underwent surgery in our hospital from January 2004 to December 2007 and who also received adjuvant chemotherapy after surgery, were analyzed in this study. Expression of TopIIα and Ki67 in paraffin-embedded tissues was detected by immunohistochemistry (IHC). The relationships between clinicopathological characteristics, chemotherapy regimens, the expression of biomarkers and disease free survival (DFS) were analyzed.

Results: TopIIα and Ki67 were highly expressed in 22.5% and 36.4% of the 151 patients, respectively. Univariate survival analysis showed that male sex (P = 0.036), non-adenocarcinoma (P = 0.004), earlier pathological TNM stage (P = 0.001) or pathological N stage (P < 0.001), and high expression of TopIIα (P = 0.012) were correlated with better DFS, whereas age, smoking history, different chemotherapy regimens, T stage and expression level of Ki67 were of no prognostic significance. Further stratified analysis showed that vinorelbine (NVB)-containing adjuvant regimens were generally associated with better DFS than regimens without NVB in patients with low TopIIα expression, though the difference was not statistically significant (P = 0.065). Pairwise comparisons for patients with low TopIIα expression indicated that the NVB-containing regimen was associated with better DFS than the docetaxel (TXT)-containing regimen (P = 0.047). COX multivariate analysis showed that pathological TNM stage, histological subtype and expression level of TopIIα to be independent of risk factors affecting DFS in postoperative NSCLC patients who received chemotherapy.

Conclusions: High TopIIα expression was discovered to be correlated with better DFS for postoperative NSCLC patients who received adjuvant chemotherapy. The NVB-containing chemotherapy regimen was more effective than the TXT-containing regimen in improving DFS in patients with low TopIIα expression. TopIIα could be considered to be an independent prognostic biomarker of DFS in postoperative NSCLC patients who received adjuvant chemotherapy.

Figure 1

Positive expression of TopIIα and Ki67 in non-small cell lung cancer by immunohistochemistry using the EnVision two-step method. (A) and (B) correspond to ×200 and ×400 magnification of TopIIα respectively; (C) and (D) correspond to ×200 and ×400 magnification of Ki67 respectively

Figure 2

DFS curves according to different clinical and pathological characteristics. DFS curves according to: (A) sex; (B) pathological TNM stage; (C) histological subtype; (D) TopIIα expression level

Figure 3

Comparison of DFS rates among different chemotherapy subgroups in patients with low TopIIα expression. (A) depicts comparison of DFS curves between the NVB regimen group and the group of other regimens without NVB; (B) depicts comparison of DFS curves among four chemotherapy subgroups