Prognostic value of mutant p53, Ki-67, and TTF-1 and their correlation with EGFR mutation in patients with non-small cell lung cancer.

Abstract

Introduction. The clinical characteristics of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation have been well studied. However, the correlation of EGFR mutation with mutant p53, Ki-67, and thyroid transcription factor 1 (TTF-1) and their prognostic value remain indistinct. Material and methods. Clinical and pathological characteristics and overall survival were analysed retrospectively in 523 surgically resected NSCLC patients. The expression levels of p53, Ki-67, and TTF-1 protein were detected by immunohistochemistry, and an amplification refractory mutation system was used to access the status of EGFR mutations. Results. Of 523 patients with surgically resected NSCLC, 210 patients (38.4%) harboured EGFR mutations. Compared to the EGFR wild-type lung cancer, mutated EGFR harboured significantly increased mutant p53-positive or TTF-1-positive tumors (P<0.001 and <0.001, respectively). Former or current smokers, pathological stage and mutant p53-or TTF-1-positive status were independent predictors of EGFR mutation (P=0.001, 0.014, 0.014 and <0.001, respectively). Patients with p53 under expression had significantly better overall survival in the whole cohort and wild-type EGFR cohort (P=0.0010 and 0.0020, respectively) as well as in Ki-67-negative and TTF-1-positive patients (P<0.0001 and 0.0009, and P<0.0001 and 0.0004, respectively). Interestingly, in patients harbouring EGFR mutations, p53-under expression and Ki-67-negative cases still had better survival than positive cases, whereas there was no obvious difference between TTF- 1-negative and TTF-1-positive cases (P=0.0198, 0.0068 and 0.3684, respectively). Finally, in NSCLC patients with wild-type EGFR, positive Ki-67 expression was the independent predictor for the worst survival (P=0.022). Conclusion. The expression levels of mutant p53, Ki-67, and TTF-1 were correlated with EGFR mutation. High expression of mutant p53 and Ki-67 correlated with poor survival in the entire cohort, EGFR mutation or wild-type cohort. In addition, Ki-67 might have an impact on the prognosis for patients with NSCLC with wild-type EGFR.