Detecting the spectrum of multigene mutations in non-small cell lung cancer by Snapshot assay / 癌症

As molecular targets continue to be identified and more targeted inhibitors are developed for personalized treatment of non-small cell lung cancer (NSCLC), multigene mutation determination will be needed for routine oncology practice and for clinical trials. In this study, we evaluated the sensitivity and specificity of multigene mutation testing by using the Snapshot assay in NSCLC. We retrospectively reviewed a cohort of 110 consecutive NSCLC specimens for which epidermal growth factor receptor (EGFR) mutation testing was performed between November 2011 and December 2011 using Sanger sequencing. Using the Snapshot assay, mutation statuses were detected for EGFR, Kirsten rate sarcoma viral oncogene homolog (KRAS), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), v-ras neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen activated protein kinase kinase 1 (MEK1), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (HER2) in patient specimens and cell line DNA. Snapshot data were compared to Sanger sequencing data. Of the 110 samples, 51 (46.4%) harbored at least one mutation. The mutation frequency in adenocarcinoma specimens was 55.6%, and the frequencies of EGFR, KRAS, PIK3CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively (P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity was 100% (positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.

Clinical outcomes of serolimus-eluting stents versus bare metal stents in ST-segment elevation myocardial infarction patients: a meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The benefits and safety of sirolimus-eluting stent (SES) have not been systematically quantified in different trials in ST-segment elevation myocardial infarction (STEMI) patients with primary or rescue percutaneous coronary intervention (PCI). A meta-analysis of randomised trials comparing SES and bare-metal stent (BMS) was performed.</p><p><b>METHODS</b>A systematic literature search was conducted to identify all randomized clinical trials. The primary outcome was the rate of major adverse cardiac events (MACEs). The secondary outcomes included death, recurrent myocardial infarction, recurrent revascularization, and stent thrombosis.</p><p><b>RESULTS</b>Totally, 1973 STEMI patients were enrolled in seven eligible randomized trials comparing SES with BMS. The pooled rate of major adverse cardiac events was significantly lower in the SES group than in the BMS group (9.7% vs 20.3%, OR 2.45, 95% CI 1.88-3.19, P < 0.00001). No significant difference in all causes of death was found between the SES and BMS groups, as well as in the pooled recurrent myocardial infarction rates. The pooled recurrent revascularization rate was significantly lower in the SES group than in the BMS group (5.1% vs 14.8%, OR 3.30, 95% CI 2.37-4.60, P < 0.00001). No significant difference was found between the pooled rates of stent thrombosis (1.2% in the SES group and 2.0% in the BMS group, OR 1.61, 95% CI 0.79-3.26, P = 0.19).</p><p><b>CONCLUSIONS</b>SES is associated with a decreased risk of major adverse cardiac events compared with BMS by the greater reduction in repeat revascularization in STEMI patients. Larger trials with longer follow up are warranted to better define the role of SES in STEMI.</p>

Treatment of non-small-cell lung cancer with paraplatin given by two different dosage calculation methods / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the reasonable dosage for paraplatin according to different dosage calculations.</p><p><b>METHODS</b>A prospective, randomized, single-blinded study on 54 patients with advanced non-small-cell lung cancer (NSCLC) treated with paraplatin was conducted. Patients were divided to 2 groups. In group A, paraplatin dosage was calculated according to patients' body surface, and in group B, it was calculated according to the area under the curve (AUS). Hematological toxicity, response rate and survival rate in the two groups of patients were compared.</p><p><b>RESULTS</b>Neutropenia in group A and group B was seen in 77.8% and 37.0% (P < 0.05), and thrombocytopenia in 18.5% and 3.7% (P > 0.05) of patients, respectively. Hemoglobin decrease was seen in 48.2% of patients in both groups. The average quantity of paraplatin given in one cycle of treatment was 535.93 +/- 106.71 mg and 398.52 +/- 71.72 mg (P < 0.01) respectively. The average time interval between treatment cycles was 27.04 +/- 5.30 d and 22.85 +/- 2.80 d (P < 0.05). The response rate and survival rate of patients in group A and B were 22.2% versus 48.2% (P < 0.05), and 40.7% versus 44.4% (P > 0.05) respectively, but the median survival time was identical (12 months) in the two groups.</p><p><b>CONCLUSION</b>NSCLC patients given paraplatin with dosages calculated on the basis of AUC have higher response rate and less severe hematological toxicity than those given paraplatin with dosages on the basis of body surface. However, the median survival time and survival rate have no statistical differences between the two groups of patients.</p>

Expressions of E-cadherin in non-small cell lung cancer and it correlation with prognosis / 中华外科杂志

<p><b>OBJECTIVE</b>This study was to clarify E-cadherin expressions in non-small cell lung cancer (NSCLC) and its correlation with patients' prognosis.</p><p><b>METHODS</b>Tissue microarrays (TMAs) containing specimens from 365 different NSCLC were constructed, covering all stages and almost all histological types of this disease. Slides were immunohistochemically stained with antibodies against E-cadherin. Expression pattern of the protein was analyzed with relation to the clinicopathological. Correlations of the results with patients' overall survival were also examined.</p><p><b>RESULTS</b>Immunohistochemical staining revealed that E-cadherin protein was localized mainly on membranes and the cytoplasm of NSCLC tumors cells. Reduced E-cadherin expression was evident in 32.1%. Reduced E-cadherin expression significantly correlated with lymph nodes metastasis (chi(2) = 16.430, P = 0.001), histological dedifferentiation (chi(2) = 9.243, P = 0.010) and advanced clinical stage (chi(2) = 9.421, P = 0.024). There was no significant difference in E-cadherin expression between squamous cell carcinoma and adenocarcinoma. E-cadherin reduced expression correlated with a poor prognosis (P < 0.0001) in univariate analysis. Multivariate analysis showed a significantly lower survival probability for patients with reduced E-cadherin (P < 0.001), and E-cadherin was an independent prognostic factor for survival of NSCLC patients.</p><p><b>CONCLUSIONS</b>It suggests that dysfunction of E-cadherin has an important impact in the progression of lung cancer. As an independent prognostic factor, expression of E-cadherin can predict outcome of different group, together with conventional prognostic factors, and subsequently make appropriate management.</p>