Objectives: We aimed to analyze the accuracy of video-assisted mediastinoscopic lymphadenectomy (VAMLA) as a tool for preoperative staging and the impact of the technique on survival in patients with non-small cell lung cancer (NSCLC) undergoing pulmonary resection.Methods: Between May 2006 and December 2010, 433 patients underwent pulmonary resection for NSCLC, 89 (21%) had VAMLA before resection and 344 (79%) had standard mediastinoscopy. The patients who had negative VAMLA/mediastinoscopy results underwent anatomic pulmonary resection and systematic lymph node dissection.Results: The median and mean numbers of resected lymph node stations were 5 and 4.9 in the VAMLA group and 4 and 4.2 in the mediastinoscopy group (P ¼ .9). The mean number of lymph nodes per biopsy specimen using standard mediastinoscopy was 10.1, whereas it was 30.4 using VAMLA (P<.001). VAMLA unveiled N2 or N3 disease in 30 (33.7%) and in 6 (6.7%) of patients, respectively. The negative predictive value, sensitivity, false-negative value, and accuracy of VAMLA were statistically higher in the VAMLA groups compared with those of standard mediastinoscopy. The 5-year survival was 90% for VAMLA patients and 66% for mediastinoscopy patients (P ¼ .01). By multivariable analysis, VAMLA was associated with better survival (odds ratio, 1.34; 95% confidence interval, 1.1-3.2; P ¼ .02).Conclusions: VAMLA was associated with improved survival in NSCLC patients who had resectional surgery.

Chromosomal alterations are frequent events in lung carcinogenesis and usually display regions of focal amplification containing several overexpressed oncogenes. Although gains and losses of chromosomal loci have been reported copy number changes of the individual genes have not been analyzed in lung cancer. In this study 22 genes were analyzed by MLPA in tumors and matched normal tissue samples from 82 patients with non-small cell lung cancer. Gene amplifications were observed in 84% of the samples. Chromosome 8 was found to harbor the most frequent copy number alterations. The most frequently amplified genes were ZNF703, PRDM14 and MYC on chromosome 8 and the BIRC5 gene on chromosome 17. The frequency of deletions were much lower and the most frequently deleted gene was ADAM9. Amplification of the ZNF703, PRDM14 and MYC genes were highly correlated suggesting that the genes displaying high copy number changes on chromosome 8 collaborate during lung carcinogenesis.

Lung cancer is the most common cause of cancer-related death worldwide and, like many other cancers, is affected by different genetic, epigenetic, and environmental factors. The WW domain-containing oxidoreductase (WWOX) gene is a tumor-suppressor gene located on chromosome 16q23.3-24.1, and it has been shown that it loses its function due to alterations in genetic and epigenetic mechanisms. The aim of this study is to investigate the relationship between lung cancer and WWOX gene. Tumor tissue samples, corresponding normal tissues, and blood samples obtained from 50 lung cancer patients were involved in the study. We analyzed methylation profile by methylation-specific PCR and mutations and polymorphisms by DNA sequencing. Methylation analysis showed that promoter hypermethylation was present in 38 of 50 (76%) patients. In addition, promoter region of WWOX gene of younger patients was more frequently methylated than older patients. Using DNA sequencing, we found four genetic alterations in WWOX gene. Two of them were germline mutations (Exon 4 and 7), and two of them were polymorphic (Exon 6 and 8). We found a new mutation in exon 7 (Arg-254-->Cys) which has not been described previously. The changes in the short-chain dehydrogenase domain of the protein caused by the genetic alterations may affect the function of the gene. We conclude that hypermethylation of WWOX gene promoter region and mutations in the gene might be related to lung carcinogenesis.

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Despite therapeutic advances, lung cancer remains one of the most common causes of cancer‐related deaths worldwide. The ZNF703 gene has been identified as the driver of the 8p11‐12 region and its amplification or overexpression has been associated with several types of cancers. It has also been shown that ZNF703 overexpression can activate the Akt/mTOR signaling pathway. The aim of our study was to investigate the role of the ZNF703 gene in association with Akt/mTOR activation in non‐small cell lung cancer (NSCLC). Expression levels in tumors and matched noncancerous tissue samples from 47 patients were analyzed by qRT‐PCR and the Akt phosphorylation levels were investigated by Western blotting. Our results show that ZNF703 is up‐regulated in 63.4% of NSCLC tumor samples. Althogh the correlation did not reach a statistically significant level Akt phosphorylation was increased in tumor tissues expressing high levels of ZNF703. The role of the ZNF703 gene has not been investigated in NSCLC. Our data show that ZNF703 may contribute to tumor development in NSCLC by activating the Akt/mTOR pathway.

PNET is an aggressive malignancy that often requires multimodal therapy. Induction chemotherapy leads to a greater complete resection rate and better disease-free survival, while involvement of the costovertebral junction indicates a poorer survival.

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