Expression and clinical significance of PML, P53 and P16INK4A in lung cancer / 中国肺癌杂志

ABSTRACT

<p><b>BACKGROUND</b>The promyelocytic leukaemia (PML) protein has been implicated in control of key tumor-suppressive pathways. However, its role in pathogenesis of lung cancer is still unclear. The objective of this study is to assess expression and clinical significance of PML, P53 and P16INK4A in lung cancer, as well as the relation of these factors.</p><p><b>METHODS</b>The tissue microarrays were created with samples from lung cancers (n=148), pulmonary benign lung tumors (n=5) and normal lung tissues (n=7), and protein expression was analyzed by immunohistochemical staining. The association between protein expression and clinical parameters was evaluated by using Crosstabs method. The Kaplan-Meier method was used to estimate survival. Cox proportional hazards model was used for univariate and multivariate analysis.</p><p><b>RESULTS</b>There was at least triplicate 0.6-mm cores per sample, 4 cases of lung cancer were excluded for lacking of enough tissue. PML was found in the cytoplasm of 14.0% cases of NSCLC and of 39.1% SCLC (P=0.010), and in the nuclei of 31.4% NSCLC and 8.7% SCLC respectively (P=0.026). PML protein was present in 9 patients with SCLC and absent in 14 cases, 5-year cumulative survival rate of the patients was 50% and 23% respectively (Log-rank test, P=0.047). Lacking of PML protein and senior pathologic T-stage were two hazardous factors that influenced prognosis of SCLC. P53 expression was found in 33.3% lung cancer, and absent in benign tumors and normal tissues of the lung (P=0.038). P16INK4A expression was abolished in normal lung tissue, however, increased in lung cancer (28.5%), and especially in lung cancer with non- or poor differentiation (36.5%) and in SCLC (69.6%). There was inverse correlation between PML expression in the nuclei and P16INK4A expression, positive correlation between P53 and P16INK4A expressions in lung cancers. PML was negatively correlated with P53 in squamous cell carcinoma.</p><p><b>CONCLUSIONS</b>As an important suppressor of tumor, PML is related with P53 mutation in squamous cell carcinoma. Increased P16INK4A protein in lung cancer may be the results of gene mutation, and be related with mutant P53 protein.</p>