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

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

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.
Adenocarcinoma ; diagnosis ; genetics ; mortality ; pathology ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; genetics ; mortality ; pathology ; Carcinoma, Squamous Cell ; diagnosis ; genetics ; mortality ; pathology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Lung Neoplasms ; diagnosis ; genetics ; mortality ; pathology ; Lymphatic Metastasis ; Neoplasm Grading ; Neoplasm Staging ; Odds Ratio ; Prognosis ; Receptor, Epidermal Growth Factor ; genetics ; metabolism ; Survival Analysis ; Vascular Endothelial Growth Factor A ; genetics ; metabolism

Accumulating studies explored the clinicopathologic and prognostic value of programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC), but the results were controversial. We therefore conducted a meta-analysis to evaluate the predictive role of PD-L1 in NSCLC patients. We systematically collected relevant studies from PubMed, Embase, Web of Science and China National Knowledge Infrastructure. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), and odd ratios (ORs) with 95% CIs for clinicopathologic factors were calculated. A total of 15 studies involving 3605 patients were included in this meta-analysis. The results showed no prognostic role of PD-L1 in the whole patients (HR=1.60, 95% CI: 0.88-2.89, P=0.123). Subgroup analysis showed that PD-L1 was associated with decreased OS in Asian patients (HR=2.00, 95% CI: 1.55-2.57, P<0.001). Among all the clinicopathologic factors, PD-L1 overexpression was significantly in relevance with poor tumor cell differentiation (HR=1.84, 95% CI: 1.49-2.28, P<0.001), late stage (HR=1.21, 95% CI: 1.02-1.43, P=0.026) and anaplastic lymphoma kinase (ALK) translocation (HR=2.63, 95% CI: 1.08-6.40, P=0.034), but not with other factors. In conclusion, our meta-analysis demonstrated that PD-L1 has a prognostic role in Asian patients with NSCLC.
Asian Continental Ancestry Group ; B7-H1 Antigen ; genetics ; metabolism ; Biomarkers, Tumor ; genetics ; metabolism ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; ethnology ; genetics ; mortality ; European Continental Ancestry Group ; Humans ; Lung Neoplasms ; diagnosis ; ethnology ; genetics ; mortality ; Neoplasm Grading ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Protein Transport ; Receptor Protein-Tyrosine Kinases ; genetics ; metabolism

Non-small cell lung cancers (NSCLC) vary in their biologic behavior. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors. This study evaluated such immunophenotypes with regard to cell cycle regulation and proliferation, apoptosis, and angiogenesis, to determine their significance for patient outcome. Core biopsies from 219 patients with NSCLC were assembled on tissue microarrays, and the expressions of p16, p21, p27, cyclin B1, cyclin E, Ki-67, caspase-3, survivin, bcl-2, VEGF, and endostatin were evaluated by immunohistochemistry. Despite previously described prognostic relevance of some of the investigated molecules, many of those markers were not directly associated with recurrence or survival. However, there was a trend for p16 immunoreactivity to be associated with a good prognosis (57% vs. 42% in 5-yr survival) (p=0.071). bcl-2 expression was strongly correlated with a better outcome (65% vs. 45% in 5-yr survival) (p=0.029), and the hazard of death for bcl-2 positive patients was 0.42 times of that for bcl-2 negative patients (p=0.047). A multivariate analysis with Cox proportional hazards model confirmed that the lymph node status (p=0.043) and stage (p=0.003) were other independent prognostic factors. Our results suggest that p16 and bcl-2 provide prognostic information independent of the TNM stage in NSCLC.
Tumor Markers, Biological/*analysis ; Survival Rate ; Survival Analysis ; Statistics ; Sensitivity and Specificity ; Reproducibility of Results ; Prognosis ; Outcome Assessment (Health Care)/*methods ; Neoplasm Proteins/*analysis ; Male ; Lung Neoplasms/*diagnosis/*metabolism/mortality ; Korea/epidemiology ; Humans ; Female ; Carcinoma, Non-Small-Cell Lung/*diagnosis/*metabolism/mortality ; Aged