Carcinoma, Non-Small-Cell Lung ; blood ; mortality ; Female ; Humans ; Male ; Vascular Endothelial Growth Factor A ; metabolism

BACKGROUNDTranscription factor Pokemon, a central regulation gene of the important tumor suppressor ARF gene, exerted its activity by acting upstream of many tumor-suppressing genes and proto-oncogenes. Its expression in non-small cell lung cancer (NSCLC) and its clinical significance remains unclear. The aim of this study was to investigate the expression of Pokemon in NSCLC and to explore its correlation with the clinical pathological characteristics and its influence on patients' prognosis.

METHODSFifty-five cases of NSCLC were involved in this study. The expression of Pokemon in the tumor tissue, the corresponding tumor adjacent tissue and the surrounding tissue was detected via reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, with the aim of investigating the correlation between the expression of Pokemon in tumor tissue of NSCLC and its clinical pathological characteristics. Moreover, a prognostic analysis was carried out based upon the immunohistochemical (IHC) detection of the expression of Pokemon gene in archival tumor specimens (5 years ago) of 62 cases of NSCLC.

RESULTSStatistical significance of the expression of Pokemon mRNA and protein was determined in the tumor tissue, the tumor adjacent tissue and the surrounding tissue (P<0.05). The expression of Pokemon was determined not to be associated with the patients' sex, age, smoking condition, tumor differentiation degree, histology and lymph node metastasis condition. However, its relationship with TNM staging was established (P<0.05). Furthermore, it was shown that the survival rate of patients with negative Pokemon expression was significantly higher than that of those with positive Pokemon expression (P=0.004), therefore, the expression of Pokemon is believed to be an independent factor affecting prognosis (P=0.034).

CONCLUSIONPokemon was over-expressed in NSCLC tissue and the expression of Pokemon might be of clinical significance in non-small cell lung cancer prognostic evaluation.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; mortality ; Male ; Middle Aged ; RNA, Messenger ; analysis ; Transcription Factors ; analysis ; genetics

OBJECTIVE: To explore the expression patterns of transcription factor SOX12 in lung adenocarcinoma and its significance in the diagnosis and prognosis of the malignancy. METHODS: Large cancer genome databases were used to analyze SOX12 expression level in lung adenocarcinoma. Immunohistochemistry (IHC) and semiquantitative PCR were used to detect the expression of SOX12 in 36 specimens of lung adenocarcinoma tissues, 15 adjacent tissues and 21 normal lung tissues. The prognostic value of SOX12 in lung adenocarcinoma and lung squamous cell carcinoma were analyzed using Kaplan-Meier Plotter database, and the relationship between SOX12 expression and the overall survival (OS) and progression free survival (PPS) of the patients were analyzed. RESULTS: Analysis of TCGA database and GEO (GSE40419) database showed that SOX12 expression levels were significantly higher in in lung adenocarcinoma than in normal lung tissues ( < 0.001). The results of IHC and semiquantitative PCR revealed that SOX12 was expressed at significantly higher levels in lung adenocarcinoma than in normal lung tissues ( < 0.001). Kaplan-Meier survival analysis showed that patients with lung adenocarcinoma positive for SOX12 had a significantly shorter OS and PPS time than those negative for SOX12 ( < 0.05), but SOX12 positivity did not significantly affect OS and PPS of patients with lung squamous cell carcinoma. CONCLUSIONS High expression levels of SOX12 in lung adenocarcinoma are significantly associated with a poor OS of the patients, suggesting the value of SOX12 to assist in early diagnosis and prognostic evaluation of lung adenocarcinoma.
Adenocarcinoma ; metabolism ; Adenocarcinoma of Lung ; metabolism ; mortality ; Biomarkers, Tumor ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; Databases, Factual ; Humans ; Kaplan-Meier Estimate ; Lung Neoplasms ; metabolism ; mortality ; Prognosis ; SOXC Transcription Factors ; metabolism ; Transcription Factors

OBJECTIVEThe aim of this study was to investigate the prognostic value of combined expression of Aurora A, Ki-67, p53 and p21 WAF1 in patients after curative resection of non-small cell lung cancer (NSCLC).

METHODSExpressions of Aurora A, Ki-67, p53 and p21 WAF1 in 58 tumor samples from resected primary NSCLCs were detected by immunohistochemistry. The correlation of proteins, survival and clinicopathological characteristics was analyzed.

RESULTSThe positive rates of Aurora A, Ki-67, p53 and p21 WAF1 expression were 89.7% (52/58), 53.4% (31/58), 46.6% (27/58) and 34.5% (20/58), respectively. Aurora A expression was positively correlated with nodal metastasis (69.2% vs. 37.8%, P = 0.045). The univariable analysis showed that the overall survival (OS) was 75.0%in patients with low Aurora A expression and 46.0% in patients with high Aurora A expression (P = 0.039). The 3-year survival rate was 40.0% in patients with positive expression of Aurora A and p53, 65.0% in the patients with positive expression of Aurora A or p53, and 82.1% in the patients with negative expression of Aurora A and p53 (P = 0.039). The Cox regression model showed that combined expression of Aurora and p53 is an independent factor affecting the prognosis of NSCLC patients (P = 0.015).

CONCLUSIONSOur findings suggest that the positive expression of Aurora A, Ki-67 and p53 proteins is an unfavorable factor affecting the prognosis for NSCLC patients, and the overexpression of Aurora A is an independent unfavorable factor association with shorter OS in NSCLC patients. Detection of positive Aurora A and p53 expression may be a useful predictive prognostic indicator for NSCLC patients.

Aurora Kinase A ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; surgery ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Humans ; Immunohistochemistry ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; surgery ; Prognosis ; Survival Analysis ; Survival Rate ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo investigate the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1), and their relationship to behaviors of the non-small-cell lung cancer.

METHODSThe study included 86 patients with non-small-cell lung cancer. A rapid immunohistochemical method (streptoavidin-peroxidase, SP) was used to detect VEGF and ICAM-1 expression. All patients were treated surgically and without preoperative radio- or chemotherapy.

RESULTSThe positive expression of VEGF was significantly correlated with the lymph node metastasis, TNM stage, prognosis and hematogenous tumor metastasis positively, but ICAM-1 was negatively. For patients with positive expression of VEGF and negative expression of ICAM-1, the 5-year survival rate was the lowest in all patients.

CONCLUSIONSThe expression of VEGF and ICAM-1 correlates with the malignant behavior of non-small-cell lung cancer. Examination of VEGF and ICAM-1 in non-small-cell lung cancer may help to evaluate its intensity of lymph node metastasis, TNM stage and prognosis. VEGF and ICAM-1 may play an important role in the development and metastasis of non-small-cell lung cancer.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; pathology ; Female ; Humans ; Immunohistochemistry ; Intercellular Adhesion Molecule-1 ; metabolism ; Lung Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Staging ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism

This study was aimed to evaluate the prevalence and prognostic implication of thyroid transcription factor-1 (TTF-1) immunoreactivity in 81 human lung carcinomas, including 65 cases of non-small cell lung carcinoma (NSCLC) and 16 cases of small cell lung carcinoma (SCLC); and also to investigate its relationship with the cell proliferation and regulation by immunostaining of Ki-67 and p53 proteins, respectively. The immunohistochemical staining for TTF-1(clone 8G7G3/1) was performed and several clinicopathologic variables and the follow-up data were obtained. The immuno-staining results for TTF-1 were semiquantitatively interpreted as negative and positive. Of NSCLCs, TTF-1 is highly expressed in adenocarcinomas (76%), whereas squamous cell carcinomas revealed no immunoreactivity (0%). SCLCs showed strong TTF-1 expression (88%). In NSCLC, TTF-1 expression was inversely correlated with Ki-67 proliferative activity and independent of p53 overexpression. TTF-1(+) group tended to show better survival than TTF-1(-) group in NSCLC. Conclusively, these observations suggest that TTF-1 is a sensitive and specific diagnostic marker for pulmonary adenocarcinomas and SCLCs; that TTF-1 might have a good prognostic implication based on its inverse correlation with Ki-67 proliferative activity and tendency for better survival in NSCLC; that this cell lineage marker may play a role in the molecular pathogenesis of lung cancers at the level of transcription.
Adenocarcinoma/diagnosis/metabolism ; Adult ; Aged ; Carcinoma, Non-Small-Cell Lung/diagnosis/*metabolism/mortality ; Carcinoma, Small Cell/diagnosis/*metabolism/mortality ; Cell Division ; Cell Line, Tumor ; Cell Lineage ; Female ; Human ; Immunohistochemistry ; Ki-67 Antigen/*biosynthesis ; Lung Neoplasms/diagnosis/*metabolism/mortality ; Male ; Middle Aged ; Nuclear Proteins/*biosynthesis ; Prognosis ; Protein p53/*biosynthesis ; Sensitivity and Specificity ; Time Factors ; Transcription Factors/*biosynthesis ; Transcription, Genetic ; Tumor Markers, Biological

BACKGROUNDPatients with single station mediastinal lymph node (N2) non-small cell lung cancer (NSCLC) have a better prognosis than those with multilevel N2. The molecular factors which are involved in disease progression remain largely unknown. The purpose of this study was to investigate gene expression differences between single station and multilevel N2 NSCLC and to identify the crucial molecular factors which are associated with progress and prognosis of stage N2 NSCLC.

METHODSGene expression analysis was performed using Agilent 4×44K Whole Human Genome Oligo Microarray on 10 freshfrozen lymph node tissue samples from single station N2 and paired multilevel N2 NSCLC patients. Real-time reverse transcription (RT)-PCR was used to validate the differential expression of 14 genes selected by cDNA microarray of which four were confirmed. Immunohistochemical staining for these validated genes was performed on formalin-fixed, paraffinembedded tissue samples from 130 cases of stage N2 NSCLC arranged in a high-density tissue microarray.

RESULTSWe identified a 14 gene expression signature by comparative analysis of gene expression. Expression of these genes strongly differed between single station and multilevel N2 NSCLC. Four genes (ADAM28, MUC4, CLDN1, and IGF2) correlated with the results of microarray and real-time RT-PCR analysis for the gene-expression data in samples from 56 NSCLC patients. Immunohistochemical staining for these genes in samples from 130 cases of stage N2 NSCLC demonstrated the expression of IGF2 and CLDN1 was negatively correlated with overall survival of stage N2 NSCLC.

CONCLUSIONSOur results suggest that the expression of CLDN1 and IGF2 indicate a poor prognosis in stage N2 NSCLC. Further, CLDN1 and IGF2 may provide potential targeting opportunities in future therapies.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; pathology ; Claudin-1 ; analysis ; genetics ; Female ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor II ; analysis ; genetics ; Lung Neoplasms ; metabolism ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis

OBJECTIVEThis study was to clarify E-cadherin expressions in non-small cell lung cancer (NSCLC) and its correlation with patients' prognosis.

METHODSTissue microarrays (TMAs) containing specimens from 365 different NSCLC were constructed, covering all stages and almost all histological types of this disease. Slides were immunohistochemically stained with antibodies against E-cadherin. Expression pattern of the protein was analyzed with relation to the clinicopathological. Correlations of the results with patients' overall survival were also examined.

RESULTSImmunohistochemical staining revealed that E-cadherin protein was localized mainly on membranes and the cytoplasm of NSCLC tumors cells. Reduced E-cadherin expression was evident in 32.1%. Reduced E-cadherin expression significantly correlated with lymph nodes metastasis (chi(2) = 16.430, P = 0.001), histological dedifferentiation (chi(2) = 9.243, P = 0.010) and advanced clinical stage (chi(2) = 9.421, P = 0.024). There was no significant difference in E-cadherin expression between squamous cell carcinoma and adenocarcinoma. E-cadherin reduced expression correlated with a poor prognosis (P < 0.0001) in univariate analysis. Multivariate analysis showed a significantly lower survival probability for patients with reduced E-cadherin (P < 0.001), and E-cadherin was an independent prognostic factor for survival of NSCLC patients.

CONCLUSIONSIt suggests that dysfunction of E-cadherin has an important impact in the progression of lung cancer. As an independent prognostic factor, expression of E-cadherin can predict outcome of different group, together with conventional prognostic factors, and subsequently make appropriate management.

Adult ; Aged ; Aged, 80 and over ; Cadherins ; biosynthesis ; Carcinoma, Non-Small-Cell Lung ; metabolism ; mortality ; secondary ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; mortality ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Survival Rate

OBJECTIVETo evaluate the expression of fatty acid synthase (FAS) in non-small cell lung cancer (NSCLC).

METHODSFAS was examined by immunohistochemical S-P technique in 175 specimens of NSCLC patients. Multiple clinical factors were analyzed according to their relation with expression of FAS.

RESULTSThe overall FAS expression rate was 31.4% (55/175). The expression of FAS in the non-adenocarcinoma patients was significantly higher than that of adenocarcinoma patients (38.4% vs 22.4%, P = 0.036). Higher FAS expression was also detected in patients who had vascular invasion or bone metastasis than those without (75.0% vs 29.3%, P = 0.02 and 46.9% vs 28.0%, P = 0.037). But, there was no significant difference between FAS and other clinical factors such as age, sex, smoking index, tumor size, stage, degree of differentiation, lymphatic metastasis, local recurrence or distant metastasis. Although there was no significant difference in the survival rates of FAS positive and negative patients (P = 0.066), the survival rate of FAS positive stage I patients was lower than that of negative ones (P = 0.005).

CONCLUSIONFatty acid synthase in the specimens of non-small cell lung cancer patients has no correlation with most clinical factors, except that, in early lesions, it may signify poor prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; enzymology ; metabolism ; mortality ; Fatty Acid Synthases ; biosynthesis ; Female ; Gene Expression ; Humans ; Lung Neoplasms ; diagnosis ; enzymology ; metabolism ; mortality ; Male ; Middle Aged ; Prognosis ; Survival Rate

Using immunohistochemical staining, we studied the relationship between the microvessel count (MC) and the expression of K-ras, mutant p53 protein, and vascular endothelial growth factor (VEGF) in 61 surgically resected non-small cell lung cancers (NSCLC) (42 squamous cell carcinoma, 14 adenocarcinoma, 2 large cell carcinoma, 2 adenosquamous carcinoma, and 1 mucoepidermoid carcinoma). MC of the tumors with lymph node (LN) metastasis was significantly higher than that of tumors without LN metastasis (66.1+/-23.1 vs. 33.8+/-13.1, p<0.05). VEGF was positive in 54 patients (88.5%). MC was 58.1+/-25.2 (mean+/-S.D.) in a x200 field, and it was significantly higher in VEGF(+) tumors than in VEGF(-) tumors (61.4+/-23.7 vs. 32.9+/-23.8, p<0.05). VEGF expression was higher in K-ras-positive or mutant p53-positive tumors than in negative tumors (p<0.05). MC was significantly higher in K-ras(+) tumors than in K-ras(-) tumors, although it did not differ according to the level of mutant p53 protein expression. Survival did not differ with VEGF, mutant p53, or K-ras expression, or the level of MC. In conclusion, there is a flow of molecular alterations from K-ras and p53, to VEGF expression, leading to angiogenesis and ultimately lymph node metastasis. Correlations between variables in close approximation and the lack of prognostic significance of individual molecular alterations suggest that tumorigenesis and metastasis are multifactorial processes.
Adult ; Aged ; Carcinoma, Non-Small-Cell Lung/*blood supply/chemistry/mortality ; Endothelial Growth Factors/*analysis ; Female ; Human ; Lung Neoplasms/*blood supply/chemistry/mortality ; Lymphokines/*analysis ; Male ; Middle Age ; Neovascularization, Pathologic/*metabolism ; Protein p53/*analysis ; Survival Rate ; ras Proteins/*analysis