Unlimited cell proliferation is a character of malignancy. MIB-1 is a DNA-binding nuclear protein expressed throughout the cell cycle in proliferating but not in quiescent (G0) cells. MIB-1 labeling index (LI) is measured to evaluate a malignant potential of tumors. The purpose of our study is to develop its prognostic and predictive role.
A total of 633 non-small cell lung cancer (NSCLC) were surgically resected from 2002 to 2011. Male:Female ratio was 246:387; range of age was between 32 and 89 years old and the mean age was 69.1 years old. Follow up duration was from 1.6 months to 143.1 months and the mean duration was 27.8 months. MIB-1 LI was assessed by immunohistochemistry and automated analyzer, and correlated with clinicopathological background including patients' outcome and adjuvant chemotherapy.
MIB-1 LI was related with disease-free survival and overall survival in both adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). In ADC, high MIB-1 LI (optimized validated cut off: 10.6%) was an independent negative prognosticator (Hazards ratio: 2.53, 95% Confidential interval: 1.69-3.77, p < 0.01). In SQCC, high MIB-1 LI (cut off: 27.1%) was an independent negative prognosticator (Hazards ratio: 2.46, 95% Confidential interval: 1.42-4.25, p < 0.01). Survival differences were influenced by adjuvant chemotherapy. In pstage II/III ADC, the patients with MIB-I LI high/adjuvant chemotherapy had a better prognosis than the patients with MIB-1 LI high/no adjuvant chemotherapy (Median survival time: 48.6 months vs. 18.4 months, Hazards ratio: 0.77, p = 0.54), although not significantly. In pstage II/III SQCC, the patients with MIB-1 LI high/adjuvant chemotherapy had a better prognosis than the patients with MIB-1 LI high/no adjuvant chemotherapy (Median survival time: 62.3 months vs. 32.2 months, Hazards ratio: 0.45, p = 0.13), although not significantly. On the other hand, there was no difference in the patients with MIB-1 LI low both ADC and SQCC.
Our study shows MIB-1 LI was different among histologic subtypes. By arranging an appropriate cut off value, MIB-1 LI is a useful biomarker to predict patients' outcome and effect of chemotherapy in NSCLC.
Clinical trial identification
All authors have declared no conflicts of interest.