Emphysema is an independent risk factor for 5-year mortality in patients with bronchiectasis.

INTRODUCTION: Bronchiectasis is a common disabling respiratory disease in China. However, the literatures that focused on the long-term prognosis and the risk factors for mortality are limited. OBJECTIVE: The aim of this study was to identify risk factors for 5-year mortality in patients with bronchiectasis. METHODS: A retrospective study was conducted. Patients who were newly diagnosed with bronchiectasis by thoracic conventional CT scans from January 2003 to March 2008 were assessed. Baseline characteristics, symptoms, radiographic extent, pulmonary function tests data and comorbidities were recorded through chart review. The vital status of the patients was obtained by telephone contact and record of hospital admission. Multivariate cox regression analysis was used to determine the independent risk factors for 5-year mortality. RESULTS: Eighty-nine patients newly diagnosed with bronchiectasis were included in our cohort. The mean age of the cohort was 55.29 ± 16.15 and 49.4% of the patients were female. At the end of the study, 12 patients (13.5%) died and the mean survival time was 57.05 ± 1.09 months. Multivariate analysis revealed that long-term mortality was significantly associated with emphysema (HR, 5.62; 95% confidence interval [CI], 1.35-23.46; P = 0.02) and radiographic extent (HR, 1.62; 95% CI, 1.02-2.58; P = 0.04). CONCLUSION: The main finding of our study was that emphysema might be a risk factor for mortality in patients with bronchiectasis.

The prevalence and prognostic significance of KRAS mutation subtypes in lung adenocarcinomas from Chinese populations.

BACKGROUND: We performed this retrospective study to identify the prevalence of KRAS mutation in Chinese populations and make a comprehensive investigation of the clinicopathological features of KRAS mutation in these patients. PATIENTS AND METHODS: Patients from 2007 to 2013 diagnosed with primary lung adeno-carcinoma who received a radical resection were examined for KRAS, EGFR, HER2, BRAF mutations, and ALK, RET, and ROS1 fusions. Clinicopathological features, including sex, age, tumor-lymph node-metastasis stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed. RESULT: KRAS mutation was detected in 113 of 1,368 patients. Nine different subtypes of KRAS mutation were identified in codon 12, codon 13, and codon 61. KRAS mutation was more frequently found in male patients and former/current smoker patients. Tumors with KRAS mutation had poorer differentiation. Invasive mucinous adenocarcinoma predominant and solid predominant subtypes were more frequent in KRAS mutant patients. No statistical significance was found in relapse-free survival or overall survival between patients with KRAS mutation and patients with other mutations. CONCLUSION: In Chinese populations, we identified KRAS mutation in 8.3% (113/1,368) of the patients with lung adenocarcinoma. KRAS mutation defines a molecular subset of lung adenocarcinoma with unique clinicopathological features.

Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations.

PURPOSE: We performed this retrospective study to have a comprehensive investigation of the clinicopathological characteristics of ALK fusion-positive lung adenocarcinoma in Chinese populations. METHODS: We screened 1407 patients with primary lung adenocarcinoma from October 2007 to May 2013. Quantitative real-time PCR (qRT-PCR), reverse transcriptase PCR (RT-PCR), and fluorescence in situ hybridization were performed to detect ALK fusion genes, with validation of positive results using immunohistochemistry. Clinicopathological characteristics were collected to assess prognosis in ALK fusion-positive patients. RESULTS: Of 1407 patients with lung adenocarcinoma, there were 74 (5.3 %) ALK fusion-positive patients. Patients harboring ALK fusion were significantly younger (56.0 years vs. 59.8 years p = 0.002) and were more likely to have advanced stages (stage III or stage IV) (OR 1.761; 95 % CI 1.10-2.82, p = 0.017). Lepidic predominant adenocarcinoma was rarely found in ALK fusion patients (2.7 vs. 13.5 % p = 0.025), while IMA (invasive mucinous adenocarcinoma) predominant adenocarcinoma was more frequently found (21.6 vs. 5.0 % p < 0.001). ALK fusion was neither a risk factor nor protective factor in relapse-free survival and overall survival. Male, current smoker, and EML4-ALK variant 3 indicated poor prognosis among ALK fusion-positive lung adenocarcinomas. CONCLUSIONS: ALK fusion was detected in 5.3 % (74/1407) of the Chinese patients with lung adenocarcinoma. ALK fusion defines a molecular subset of lung adenocarcinoma with unique clinicopathological characteristics. Different ALK fusion variants determine distinct prognoses.

Prevalence and Clinicopathological Characteristics of BRAF Mutations in Chinese Patients with Lung Adenocarcinoma.

BACKGROUND: This study was designed to identify the prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma, and to reveal the association between BRAF mutations and clinicopathological characteristics in these patients. METHODS: From October 2007 to February 2013, patients with newly diagnosed primary lung adenocarcinoma were detected for mutations in BRAF, EGFR, KRAS, HER2 and ALK. Clinicopathological characteristics, including sex, age, TNM stage, tumor differentiation, smoking status, histological subtypes, and survival information were analyzed. RESULTS: Of 1358 patients with lung adenocarcinoma, 20 patients were harboring BRAF mutations, including five BRAF V600E mutations and 15 BRAF non-V600E mutations. Among these, BRAF N581I and BRAF G593S were newly reported. BRAF mutations were associated with smoking status (odds ratio 3.28; 95 % CI 1.33-8.08; p = 0.008). In patients less than 60 years of age, BRAF mutations tended to have poor differentiation in tumor samples (70.0 vs. 35.1 %; p = 0.014), and were more likely to relapse (70 vs. 28 %; p = 0.008). A significant difference was found in relapse-free survival (RFS) between BRAF mutations and other mutations, but not in overall survival. CONCLUSIONS: The prevalence of BRAF mutations in Chinese patients with lung adenocarcinoma was approximately 1.5 %. BRAF mutations were more frequent in current smokers. Patients harboring BRAF mutations had a higher rate of recurrence and worse RFS compared with other patients.

Recurrent TERT promoter mutations in non-small cell lung cancers.

INTRODUCTION: The recurrent TERT promoter mutations have been recently described in diverse human cancers. We previously showed that over 60% of non-small cell lung cancer from East Asian harbored well-known oncogenic mutations in EGFR and KRAS. Here, we sought to determine the incidence, clinicopathologic characteristics, and association with known oncogenic mutations. PATIENTS AND METHODS: A total of 467 patients treated surgically for primary lung cancer were examined for mutations in TERT promoter using polymerase chain reaction (PCR) followed by Sanger sequencing. Immunohistochemical (IHC) staining was performed to detect the expression of TERT. Clinical characteristics including gender, age, smoking status, tumor size, differentiation, lymph node metastasis, TNM stage, overall survival and relapse-free survival were analyzed. RESULTS: Of 467 patients with non-small cell lung cancer, the TERT promoter mutation was detected in 12 patients. Of the 12 patients, 3 with C228T, 2 with C250T, 2 with C216T, 1 with C228A, 1 with C229G, 1 with G267C, 1 with C295T and 1 with G233C. Compared to the TERT mutation negative group, patients with TERT promoter mutation were significantly associated with older age (≥ 60 years, p = 0.039). No significant difference was found in overall survival (OS) or relapse-free survival (RFS) between TERT with mutation and TERT without mutation. CONCLUSIONS: TERT promoter mutations are recurrent mutated in 2.57% of NSCLCs and are highly enriched in older patients. It may play an important role in the pathogenesis of NSCLC and may serve as a potential target for therapy.

Comparison of clinical features, molecular alterations, and prognosis in morphological subgroups of lung invasive mucinous adenocarcinoma.

PURPOSE: We performed this analysis to distinguish the differences in two subtypes of lung invasive mucinous adenocarcinoma (IMA) with different kinds of morphological performances, in clinicopathological and molecular features, as well as prognosis. METHODS: On the basis of morphological performance, we divided lung IMAs into two subgroups, mucus-in-cell adenocarcinoma (MICA) and mucus-out-of-cell adenocarcinoma (MOCA). We investigated differences in clinicopathological characteristics, recurrence-free survival (RFS), overall survival (OS), and a spectrum of well-identified driver-gene mutations, including EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET, between the two subgroups. RESULTS: Of 1,699 lung adenocarcinomas, 148 were identified as IMAs (97 MICAs and 51 MOCAs). The MICA patient group had significantly better RFS than did the MOCA group (39.4 months versus 33.0 months, respectively, log rank P=0.020) and significantly better OS (54.2 months versus 45.1 months, log rank P=0.034). There were no differences in RFS and OS between those with IMAs and those with mucus-negative adenocarcinomas. The frequency of the EGFR gene mutation was significantly higher in MOCAs than in MICAs (P<0.001). In contrast, the KRAS gene had a significantly higher mutational frequency in MICAs (P=0.01). MOCAs also had a significantly higher incidence of lymph-node metastasis (P<0.05). CONCLUSION: To our knowledge, this study represents the first comparison of clinical features, molecular alterations, and prognosis in morphological subgroups of lung IMAs. Clinical and pathological features in conjunction with molecular data indicate that IMA should be divided into different subgroups.