Tumor-infiltrating Foxp3+ Tregs were positively correlated with intratumoral COX-2 expression and were associated with a worse RFS, especially among patients with node-negative NSCLC.

The prognosis of patients with NSCLC recurrence after surgery is currently improving. Our results suggested two new prognostic factors, adjuvant chemotherapy and EGFR mutations, neither of which have been previously reported. Treatment strategies for postoperative recurrence should be established based on a more detailed subdivision of factors, such as histology and molecular markers, in the future.

The role of the epidermal growth factor receptor (EGFR)/Posphorylated-Akt (P-Akt) signaling axis in regulating hypoxia-inducible factor-1alpha (HIF-1alpha) expression in vivo is not well understood and is of potential clinical importance since the extent of hypoxia in the tumor environment is thought to be an important determination of resistance to chemotherapy and radiotherapy. We performed the immunohistochemical studies in 80 patients with non-small cell lung cancers to evaluate EGFR, P-Akt, and HIF-1alpha expression. Significant correlation between P-Akt and HIF-1alpha (P=0.0006) and marginal correlation between EGFR and P-Akt (P=0.066) were found. P-Akt was shown to be a poor prognostic factor as to patients with lymph node involvement (P=0.031).

Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis. Several studies have reported that genomic VEGF polymorphisms may influence VEGF synthesis. To evaluate the role of VEGF single nucleotide polymorphisms (SNPs), we examined the expression of several angiogenesis-related proteins [VEGF, hypoxia-inducible factor-1α (HIF-1α) and delta-like ligand 4 (Dll4)] and the spread of microvessels in resected non-small cell lung cancer (NSCLC). Blood and tumor tissue from 83 patients with NSCLC were examined for VEGF −460T/C (rs833061) and VEGF +405G/C (rs2010963) SNPs using the SNaPshot method. Immunohistochemical staining was performed to measure protein expression and microvessel density (MVD). VEGF −460T/C and +405G/C SNPs showed no association with VEGF or HIF-1α expression and MVD. Patients with VEGF −460TT and the TC genotype had significantly higher MVD compared to those with the CC genotypes. Furthermore, patients with the VEGF −460TT genotype had significantly higher Dll4 expression compared to those with the TC or CC genotypes, while the VEGF +405G/C SNP displayed no association with Dll4 expression and MVD. These findings indicate that the VEGF −460T/C SNP may have a functional influence on tumor angiogenesis in NSCLC. We hypothesize that VEGF SNPs may influence angiogenesis through Dll4.

The purpose of this study was to clarify the distribution of epidermal growth factor receptor (EGFR) mutations between primary tumors (PT) and metastatic lymph node (MLN) in patients with resected non-small cell lung cancer (NSCLC) and to identify a better predictive marker of the response to EGFR tyrosine kinase inhibitor (EGFR-TKI). We conducted a retrospective review of the data of 70 lung cancer patients with lymph node metastasis who underwent surgical resection. Analysis to detect EGFR mutations was performed by a peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. EGFR mutations were detected in 15.7 % of both the PT and MLN and in 14.3 % of the PT only. The response rate to EGFR-TKI tended to be higher in patients with EGFR mutations in the MLN, as all patients with EGFR mutations in the MLN showed disease control to treatment with EGFR-TKI. Our results demonstrated that the EGFR mutation status of MLN is a predictive marker of the response to EGFR-TKI therapy in patients with recurrent NSCLC after surgical resection.

BackgroundThe purpose of this study is to clarify the correlations between the expression of membrane-bound estrogen receptor-α (mERα) and epidermal growth factor receptor (EGFR) mutation and clinicopathological factors, especially in relation to the prognosis, in patients with lung adenocarcinoma.MethodsWe conducted a retrospective review of the data of 51 lung adenocarcinoma patients with tumors measuring less than 3 cm in diameter. Immunohistochemical staining for mERα expression and detection of the EGFR mutation status were performed.ResultsAmong the 51 patients, the tumors in 15 showed both mERα expression and EGFR mutation. ("double positive") Significant associations between "double positive" and vascular invasion, vascular endothelial growth factor expression, and Ki-67 expression were observed. A multivariate analysis revealed that only "double positive" was an independent risk factor influencing the recurrence-free survival.ConclusionsPresence of mERα expression together with EGFR mutation was found to be an independent prognostic factor for survival in patients with lung adenocarcinoma, suggesting cross-talk between mERα and EGFR mutation.

A 38-year-old man without any symptoms was admitted to our institution because of an abnormal shadow found incidentally on a chest X-ray. Chest computed tomography showed a round mass in the lingular segment of the left upper lobe. Lingular segmentectomy was performed, and the histopathological diagnosis was intrapulmonary schwannoma. Immunohistochemical staining revealed a positive result for S-100 protein and negative results for CD34 and desmin. We report this case of intrapulmonary schwannoma, which is extremely rare.

Cigarette smoking is a well-known risk factor for perioperative surgery-related complications; however, steady progress in perioperative management has been made year by year. This study investigated the influence of cigarette smoking on postoperative complications in patients with lung cancer over the last three years in our institution. Clinical records of 194 patients who had undergone a pulmonary resection for lung cancer were retrospectively reviewed. The clinico-pathological findings and postoperative complications were compared among patients with smoking history. Smokers, including a higher number of men, had more preoperative respiratory complications, a lower FEV(1)/FVC, larger tumors, and included more squamous cell carcinoma in comparison to non-smokers. A univariate analysis revealed that sex, age and smoking history were independent risk factors in the postoperative complications; however, a multivariate analysis revealed that those factors including smoking history were not independent. In a subgroup of smokers subclassified by their smoking status or smoking index, there were no significant differences in postoperative complications. Over the recent three years of this study, smoking history was not a significant risk factor in postoperative complications. Especially in smokers, smoking status or smoking index was not a significant risk factor in postoperative complications, too.