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.
Adenocarcinoma ; genetics ; Carcinoma, Non-Small-Cell Lung ; genetics ; Class I Phosphatidylinositol 3-Kinases ; Genes, erbB-1 ; Genes, erbB-2 ; Genes, ras ; Humans ; Mutation ; PTEN Phosphohydrolase ; Phosphatidylinositol 3-Kinases ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins B-raf ; Proto-Oncogene Proteins p21(ras) ; Retrospective Studies ; ras Proteins

INTRODUCTION: Nontraumatic acute abdomen (NTAA) in dialysis patients is a challenging issue. The aetiologies of NTAA vary considerably depending on the renal replacement therapy (RRT) modality. Although haematological parameters and contributing factors have been reported to be associated with outcomes for dialysis patients, their clinical effect on the length of hospital stay (LOS) remains unknown. METHODS: We retrospectively analysed 52 dialysis patients (peritoneal dialysis [PD], n = 33; haemodialysis [HD], n = 19) and 30 non-dialysis patients (as controls) between January 2011 and December 2014. To attenuate the selection bias, non-dialysis patients with NTAA were matched to cases at a ratio of 1:1 by age, gender and comorbidities (diabetes mellitus and hypertension). Their demographic characteristics, laboratory data, clinical assessment scores and LOS were analysed. RESULTS: The PD group exhibited a significantly higher neutrophil percentage, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR); longer LOS; and lower lymphocyte percentage and absolute lymphocyte count than the control group. After multivariate analysis adjustment, female gender, longer RRT duration and higher intact parathyroid hormone (iPTH) levels were associated with a lower probability of being discharged home. In the dialysis group, a higher iPTH level (> 313 μg/mL) was positively correlated with longer LOS. iPTH level combined with NLR can be used as a surrogate marker for predicting longer LOS (p < 0.001). CONCLUSION NTAA dialysis patients with female gender, longer RRT duration and higher iPTH levels are prone to experiencing longer LOS. In addition, the combination of iPTH and NLR is a significant determinant for LOS in NTAA dialysis patients.