Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10(-17), per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10(-9), per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations

Identification of Early T1b Lung Adenocarcinoma Based on Thin-Section Computed Tomography Findings

IntroductionThe aim of this study was to radiologically identify early lung adenocarcinoma in clinical T1bN0M0 lung cancer, based on pathological findings and long-term prognosis.MethodsIn this study, we reviewed lung nodules findings on thin-section computed tomography in 173 patients with clinical T1bN0M0 lung adenocarcinoma who underwent surgery between 2003 and 2007. The ratio of the size of solid attenuation to the maximum tumor dimension (consolidation/tumor [C/T] ratio) was calculated. We defined two groups of patients by C/T ratio cutoff levels of 0.00, 0.25, 0.50, 0.75, and 1.00 and compared the rates of pathological nonaggressive lung adenocarcinoma, overall survival, and recurrence rates between the groups. The percentages of predominant histological subtypes were compared between two groups divided by the optimal cutoff level. Various clinical factors were analyzed by univariate and multivariate analyses to predict pathological lymph node involvement.ResultsThe median follow-up period was 62 months. All patients with C/T ratios of 0.5 or less were diagnosed as having pathological nonaggressive adenocarcinomas, and there was no recurrence; their 5-year overall survival rate was 97.4%, which was significantly better than that for patients with C/T ratios of greater than 0.5 (76.2%). None of the ground-glass opacity–predominant tumors were predominantly solid adenocarcinoma with mucin. The C/T ratio of 0.5 or more was an independent predictor of lymph node involvement.ConclusionIn patients with clinical T1bN0M0 disease, the C/T ratio of 0.5 or less identified early lung adenocarcinoma. In patients with the identified early disease, a feasibility study of limited surgery may be warranted

Impact of Extratumoral Lymphatic Permeation on Postoperative Survival of Non–Small-Cell Lung Cancer Patients

Introduction:Lymphatic permeation has been reported as a prognostic factor for patients with resected non–small-cell lung cancer (NSCLC). Lymphatic canals are located in both intratumoral and extratumoral areas. Since 2001, we have prospectively evaluated lymphatic permeation based on its location. The purpose of this study was to determine the survival impact of extratumoral lymphatic permeation in patients with resected NSCLC by analyzing the long-term follow-up data.Methods:We reviewed 1069 consecutive patients with NSCLC who underwent complete resection between 2001 and 2006. Lymphatic permeation was classified as follows: ly0, absence of lymphatic permeation; ly1, intratumoral; and ly2, extratumoral.Results:There were 845 patients (79%) with ly0, 134 (12%) with ly1, and 90 (9%) with ly2. Ly2 was more frequently observed in patients with advanced disease and intrapulmonary metastases than ly0–1. The 5-year overall survival (OS) rates of the ly0, ly1, and ly2 groups were 75%, 63%, and 34%, respectively. The OS rate was significantly worse in the ly2 group compared with OS rate in the ly0 (p < 0.01) and ly1 groups (p < 0.01). In multivariate analyses, ly2 proved to be an independent poor prognostic factor (hazard ratio, 1.73; p < 0.01). OS and recurrence-free survival of patients with T1 and T2 tumors with ly2 were not statistically different from that of the patients with T3 tumor (OS, p = 0.43 and p = 0.77; recurrence-free survival, p = 0.94 and p = 0.94, respectively).Conclusions:The adverse prognostic impact of lymphatic permeation was remarkably different whether it is detected in intratumoral or extratumoral lymphatic canals. We recommend that lymphatic permeation in resected NSCLC should be evaluated by considering its location

A Case with Significant Proteinuria Caused by Secreted Protein from Urothelial Carcinoma

58-year-old female was admitted to our hospital complaining isolated proteinuria of 1.7 g/day. Abdominal echography showed right-sided unilateral hydronephrosis, and computed tomography pointed out a tumor of the right renal pelvis, suggesting cancer of renal pelvis. The right nephroureterectomy was carried out. Pathological diagnosis was urothelial carcinoma. Renal tissue revealed no apparent glomerulopathy with tubular atrophy, interstitial fibrosis, and mildly-to-moderately interstitial mononuclear cell infiltration. Immunofluorescence study showed no deposition of immunoreactanct, and electron microscopy showed almost normal glomerulus without electron dense deposit. Proteinuria disappeared within 6 days after the operation. Moderate amount of proteinuria in our patient was probably caused by secreted protein from urothelial carcinoma. This condition is rare but should be taken into account in patients with even moderate amount of proteinuria

Prognostic Impact of CD204-Positive Macrophages in Lung Squamous Cell Carcinoma: Possible Contribution of Cd204-Positive Macrophages to the Tumor-Promoting Microenvironment

Introduction:Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 (+) TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 (+) TAMs and the clinicopathological features of lung squamous cell carcinoma.Methods:We investigated the relationships between the numbers of CD204 (+) TAMs and clinicopathological factors, microvessel density, and the numbers of Foxp3 (+) lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 (+) TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 (+) TAMs.Results:A high number of CD204 (+) TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 (+) TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 (+) TAMs were correlated with the microvessel density and the numbers of Foxp3 (+) lymphocytes. A high number of CD204 (+) TAMs was strongly correlated with the tissue expression level of monocyte chemoattractant protein-1. CD204 (+) TAMs were shown to be significant independent prognostic factors in a multivariate analysis.Conclusions:CD204 (+) TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 (+) TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments