Prognostic role of p53 and Ki-67 immunohistochemical expression in patients with surgically resected lung adenocarcinoma: a retrospective study

Cheol-Hong Kim, Hee Sung Lee, Ju-Hee Park, Jeong-Hee Choi, Seung-Hun Jang, Yong-Bum Park, Myung Goo Lee, In Gyu Hyun, Kun Il Kim, Hyoung Soo Kim, Sung Woo Cho, Won Yong Lee, Eung-Joong Kim, Haeyoung Kim, Jung Weon Shim, Young Hee Choi


Objectives: p53 mutations and the Ki-67 protein are frequently observed in various types of human cancer; the abnormal expression of p53 and Ki-67 in the tumor is associated with poor survival of lung cancer patients. We aimed to assess the prognostic role of immunohistochemical (IHC) expression of p53 and Ki-67 in lung adenocarcinoma tissue.
Methods: Tumor samples from 136 patients who had undergone surgical resection for lung adenocarcinoma were retrospectively evaluated for p53 and Ki-67 expression by immunohistochemistry. Associations of clinical and pathologic variables with p53 and Ki-67 were determined using the χ2 test. After excluding two patients (follow-up loss), 134 cases were evaluated for associations between p53, Ki-67, clinical and pathologic variables, and survival by using the Cox proportional hazards regression model and Kaplan-Meier method.
Results: In the 136 patients, p53 was positive in 71.0% (93/131), and Ki-67 showed high in 49.2% (61/124). Unlike p53, Ki-67 was associated with male sex, smoking, and poor tumor differentiation (P=0.004, P=0.001 and P=0.006). Of these, poor tumor differentiation strongly was correlated with high level of Ki-67 expression (P=0.008). Neither p53 nor Ki-67 was associated with increased risk of death (P=0.318, P=0.053); however, age ≥60 years and lymph node involvement were significant predictors of death (P=0.039 and P=0.042). The log-rank test revealed a significant association between Ki-67 and lower survival in all patients (χ2=5637; P=0.018); however, the risk was limited to stage III cases (χ2=5.939; P=0.015). Unlike p53, patients with high level of Ki-67 expression showed lower 3-year actuarial survival than those without (log-rank test, χ2=4.936; P=0.026).
Conclusions: IHC expression of Ki-67 in lung adenocarcinoma tissue shows stronger association with poor tumor differentiation, and negatively affects patients’ survival in advanced-stage lung cancer; however, the role of p53 on patient outcome needs further study.