Objective To determine the aberrant methylation status of RASSF1A,p16 and DAPK gene promoter region in induced sputum from lung cancer patients and the value of their combined detection in diagnosing lung cancers. Methods Methylation-specific PCR (MSP) was used to detect the promoter methylation status of RASSF1A,p16, and DAPK genes in induced sputum and pathological tissues from 82 patients with lung cancers and 25 patients with pulmonary benign lesion.We also analyzed the relation between methylation status and clinical pathological data.Results The positive rates of promoter methylation of RASSF1A,p16, and DAPK genes in pathological tissues from patients with lung cancers were 63.4%,59.8%, and 58.5%, respectively,and those in induced sputum were 54.9%,48.8%,and 51.2%, respectively. The promoter methylation of RASSF1A,p16, and DAPK genes were not detected in patients with pulmonary benign lesion.There was a significant difference between the lung cancer group and pulmonary benign lesion group (P＜0.05). The methylation rate of RASSF1A gene was significantly lower in the middle and high differentiation and non-metastastic lymph node of lung cancer tissues than that in the poor differentiation and the metastatic lymph node of lung cancer tissues(P＜0.05), and was not correlated with age, sex, smoking index, clinical stage, and pathological types.The methylation rate of p16, and DAPK genes was not significantly correlated with all the above mentioned factors (P＞0.05). The methylation rate of joint detecting RASSF1A, p16, and DAPK genes was 73.2%. Conclusion Joint detection for promoter hypermethylation of RASSF1A, p16, and DAPK genes in induced sputum may be used as a simple and effective index of the diagnosis and prognose of lung cancers, and can improve the positive rate.

OBJECTIVE: To investigate the expression of ubiquitin and cullin-1 (cul-1) in benign and malignant lesions of the lung and to determine their clinicopathological significance. METHODS: EnVison immunohistochemistry was used to detect the expression of ubiquitin and cul-1 in the conventional paraffin-embedded sections from the specimens of lung cancer (n = 80) and benign lesion tissues of the lung (n = 20). We also analyzed the relation of the expression of ubiquitin and cul-1 with the clinical stage, differentiation, and with or without lymphatic metastasis. RESULTS: The positive rates of ubiquitin and cul-1 were significantly higher in lung cancer (51.3% and 60.0%) than those in benign lesion tissues of the lung (20.0% and 30.0%; P < 0.05). Positive rates of ubiquitin and cul-1 were all significantly lower in the middle and high-differentiated, Stage I approximately II, and no lymphatic metastasis patients with lung cancer than those in no- or low-differentiated, Stage III approximately IV, and lymphatic metastasis patients with lung cancer tissues (P < 0.01 approximately 0.05). High consistency was found between the positive expression of ubiquitin and cul-1 in lung cancer tissues (chi(2) = 4.04, P < 0.05). CONCLUSION Expression of ubiquitin and cul-1 in lung cancer tissues may be closely related to the carcinogenesis, progression, clinical biological behaviors, and prognosis of lung cancer.
Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cullin Proteins ; genetics ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis ; Ubiquitin ; genetics ; metabolism

OBJECTIVE: To investigate the expression of von Hippel-Lindau (VHL) protein and hypoxia inducible factor-1alpha (HIF-1alpha) in the lung cancer tissue and to detect their clinical significance. METHODS: EnVisionTM immunohistochemistry was used for detecting the expression of VHL and HIF-1alpha in routinely paraffin-embedded sections from the specimens of lung cancer (n=80) and normal lung tissues (n=20). We also analyzed the relation between the expression of VHL and HIF-1alpha and the clinical stage,differentiation,and with or without lymphatic metastasis. RESULTS: The positive rate of VHL was significantly lower in lung cancer (56.3%) than that in normal lung tissues (90.0%)(P<0.01).The positive rate of HIF-1alpha was significantly higher in lung cancer (65.0%) than that in normal lung tissues (20.0%)(P<0.01). The positive rate of VHL was significantly higher in the middle and high-differentiated, StageI~II, and no-metastasis of lymph node lung cancer tissues than that in the poorly-differentiated, Stage III~IV, metastasis of lymph node lung cancer tissues (P<0.01~0.05) .But the expression of HIF-1alpha in the lung cancer tissues was just the opposite as compared with that of VHL (P<0.05) .VHL and HIF-1alpha expression levels showed highly negative correlation (P<0.01). CONCLUSION The expression of VHL and HIF-1alpha may be important biological markers for carcinogenesis, progression, clinical biological behaviors, and prognosis of lung cancer.
Adenocarcinoma ; metabolism ; pathology ; Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; metabolism ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Von Hippel-Lindau Tumor Suppressor Protein ; metabolism