Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers.

BackgroundAngiogenesis plays a significant role in complex inflammatory and angiogenic processes and is also involved in multiple myeloma (MM) pathogenesis. IL-37 is a proinflammatory cytokine in antitumor activity. Our purpose was to evaluate the IL-37 clinical significance on MM.Material/MethodsWe measured serum levels of IL-37 in 45 patients with different stages of MM and 30 healthy control subjects and correlated IL-37 with numerous cytokines, such as angiogenesis factors including vascular endothelial growth factor (VEGF) and angiotensin-2 (Ang-2). We also measured the tube formation of human umbilical vein endothelial cells (HUVECs) after pretreatment with recombinant human IL-37 (rhIL-37).ResultsSerum IL-37 level was lower in the patients with MM than in the healthy control subjects, whereas VEGF and Ang-2 levels were higher, depending on International Staging System stage. Serum IL-37 level had a negative correlation to VEGF and Ang-2 levels, and VEGF had a positive correlation to Ang-2 level. The tube formation of HUVECs was suppressed by the rhIL-37 pretreatment.ConclusionsOur results indicate that serum level of IL-37 plays a part in the pathophysiology of MM progression. Therefore, IL-37 serum level may be a biomarker for disease stage and angiogenesis processes.

The fatality rate of esophageal carcinomas is high in developing countries, making effective treatment desirable. Traditional treatment has now entered into the platform, and treatments based on the detection of biomarkers increasingly become a trend. This review presents several biomarkers of esophageal cancer, including chemotherapy-related biomarkers and targeted drug-related biomarkers, and the correlation of these biomarkers with drug response.

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Thrombocytopenia is a common manifestation of tumors, which is usually caused by myelosuppression caused by bone marrow involvement of malignant tumor cells or radiotherapy. Immune thrombocytopenia (ITP), as a paraneoplastic syndrome, is more common in lymphatic proliferative neoplasms and rheumatic diseases, less common in solid neoplasms, and has not been reported in peritoneal epithelioid mesothelioma.Herein, we report a 45-year-old patient with peritoneal epithelioid mesothelioma who received remission of thrombocytopenia after treatment with hormones, intravenous human immunoglobulin, and thrombopoietin receptor agonists, as well as subsequent surgery and chemotherapy for the tumor.

e17512 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) has been widely used in non-small cell lung cancer (NSCLC), and the incidence of EGFR mutation in NSCLC is higher in China than in the United States and European countries. EGFR exons 19 and 21 mutation in NSCLC is related to response of tumors to EGFR TKIs, suggesting its usefulness as a biomarker. Some case studies reported that gefitinib-responsive small cell lung cancer (SCLC) with EGFR mutation. However, there are few large studies which reported the mutation status of SCLC patients. It is difficult to obtain tumor tissues to detect EGFR mutation in SCLC patients especially from surgery. This aim of the study is to know the EGFR mutation status in SCLC patients in China, and evaluate the feasibility of EGFR mutation detection from plasma by mutant-enriched liquidchip (MEL) technology. Methods: From September 2011 to January 2012, 27 cases of SCLC plasmas were collected at our Hospital, China. There are 6 female, 21 male. Age from 46 to 74 years old and median age is 60 years old. The stage (Veterans Administration Lung Study Group, VALSG): limited disease (LD) 6 cases, extensive disease (ED) 21 cases. Smoking history: non-smoker 8 cases, light smoker 0 cases, moderate smoker 3 cases and heavy smoker 16 cases. MEL technology was used to detect EGFR exon 19 and exon 21 mutations from plasma of 27 SCLC patients. Results: One of 27 cases was found with mutation in exon 19 of the EGFR gene. The patient with EGFR exon 19 mutation is a female and non-smoker. Conclusions: EGFR mutation is rare in SCLC patients, and may be more easily occurred in female and non-smokers. It is feasible to detect EGFR mutation for SCLC from plasma by MEL technology.

e18142 Background: Responsiveness of non-small cell lung cancer (NSCLC) to EGFR tyrosine kinase inhibitors has been confirmed to relate to mutations in the epidermal growth factor receptor (EGFR) signaling pathway genes. This study’s aim is to detect mutations in two important components of the EGFR signaling pathway, EGFR and KRAS, using a novel liquidchip technology, and to evaluate the correspondence between tumor and plasma DNA in the same patient. Methods: 58 advanced primary NSCLC ( IIIB or ‡W) tumor tissues and matched peripheral blood samples (MPBS) were obtained. The procedures for multiplex PCR, allele specific primer extension (ASPE) and hybridization were performed after DNA extraction. A novel liquidchip platform for simultaneous detection multiple alleles of DNA somatic mutations was applied to detect the EGFR and KRAS status in matched samples. Results: EGFR exon 19 and exon 21 mutation rate was detected to be 29.3% (17/58) and 17.2% (10/58) respectively in tumor tissues, while 20.7% (12/58) and 12.1% (7/58) in MPBS. Among those 27 patients who harbor either EGFR exon 19 or exon 21 mutations in tissues, 19 (70.4%) of them were detected to have the same mutations in their peripheral blood samples. EGFR exon 20 T790M mutations were found in one of the paired samples. All the patients who were detected to have wild-type EGFR in tissues were detected to have wild-type in MPBS as well. In 50 of 58 (86.2%) of the paired samples, the EGFR mutation status in the tumors was consistent with those in the MPBS. The KRAS exon 2 mutation was also found in both blood and tumor samples in one patient; however only in the blood of another patient, not in his tumor. Conclusions: The liquidchip technology may serve as an effective method for detecting multiple gene mutations. EGFR and KRAS gene mutations in blood DNA were highly consistent with the corresponding tissue samples, and therefore, peripheral blood could be used as an alternative sample to predict patients’ response to the anti-EGFR targeted therapy. Further studies to evaluate the clinical application are suggested.

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