Two types of molecular tests have been established to assess the deficiency of the DNA mismatch repair (MMR) system: microsatellite instability (MSI) and immunohistochemical (IHC) analysis. We have developed a reliable method to analyze the MSI status by next-generation sequencing (NGS) based on read-count distribution. A total of 91 patients with primary colorectal cancer were recruited. These patients included 54 cases with loss of expression of any MMR protein in IHC, suggesting deficient MMR (dMMR), and 37 cases of colorectal cancer with staining of all four MMR proteins in IHC, suggesting proficient MMR in the sample after surgery. DNA was extracted from paired tumor-normal tissue for MSI detection by both the ColonCore NGS panel and PCR. The sequencing data from the NGS panel was processed using various MSI detection pipelines for a comparison with the ColonCore panel. Using the MSI-PCR test as the gold standard, MSI-ColonCore achieved 97.9% sensitivity (47 of 48) and 100% specificity (37 of 37) for the detection of MSI status. MSI-ColonCore also showed more efficient and robust performance compared with other NGS-based MSI detection algorithms. The concordance rate was 92.3% between MSI-ColonCore and IHC testing, and 93.4% between MSI-PCR and IHC testing. These results suggest that MSI-ColonCore is a reliable and robust method for MSI status detection by NGS based on read-count distribution.

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are the standard first line treatment for advanced non-small cell lung cancer (NSCLC) with sensitive EGFR mutations. Among NSCLC, giant cell carcinoma of the lung (GCCL) is a rare pathological subtype with poor prognosis, with no confirmed evidence about its epidemiological features or therapeutic efficiency of EGFR-TKIs. We present two advanced GCCLs with sensitive EGFR mutations, also collected the cases of GCCL from our hospital and the Surveillance, Epidemiology, and End Results (SEER) program. Kaplan-Meier methods and Cox proportional hazards modeling were used to perform the survival analyses. Both two cases of advanced GCCL with sensitive EGFR mutations benefited from EGFR-TKIs. Twelve GCCLs were recorded in our hospital from May 2006 to July 2015. GCCL is associated with males (83.3%) and smoking status (63.6%). The EGFR mutation rate was 40.0%. In SEER database, the total number of GCCLs was 184, 0.11% for all NSCLCs. In Kaplan-Meier analysis, the 5-year overall survival of GCCL patients was significantly lower than that of non-GCC NSCLC (16% and 19%; P<0.001), and it was confirmed in multivariate analysis. Further survival analyses indicated that male were more susceptible to GCCL and GCCL was prone to metastasize. Only age and M stage were independent prognostic factors for GCCL in the multivariate analysis. In conclusion, GCCL was an unfavorable prognostic factor and associated with males and metastasis. GCCL patients with sensitive EGFR mutations may also benefit from EGFR-TKI, we therefore recommend the evaluation of EGFR in the treatment of advanced GCCL.

BackgroundThe role of surgical therapy in gastric cancer patients with distant metastases remains controversial. This retrospective analysis was performed to identify whether gastric cancer patients with distant metastases might benefit from surgery.Patients and methodsA total of 5185 patients from the SEER database who were initially diagnosed with histologically confirmed gastric cancer with distant metastases from 2004 to 2009 were included. Patients were divided into the following three groups: patients who underwent resection of both the primary tumor and distant metastatic tumors (‘PMTR’ group), patients who only underwent resection of the primary tumor (‘PTR’ group) and patients who did not undergo any surgery (‘No surgery’ group). We employed the Kaplan-Meier analysis, the log-rank test and multivariate Cox proportional hazards regression models to estimate the survival time of the different groups.ResultsA total of 5185 patients had a median survival time (MST) of 9.0 months. The improvement in survival of the ‘PMTR’ and ‘PTR’ groups was significantly different compared with that of the ‘No surgery’ group (MST, 12.0 vs 12.0 vs 9.0 months, respectively, P<0.001; 1-year survival rate, 49.6% vs 49.1% vs 30.1%, respectively, P<0.001; 3-year survival rate, 12.5% vs 15.1% vs 5.8%, respectively, P<0.001), whereas no significant difference was found between the ‘PMTR’ group and ‘PTR’ group (P=0.642). Multivariate Cox proportional analysis showed that surgery was an independent prognostic factor (‘PMTR’, hazard ratio (HR) =0.648, 95% confidence interval (CI) 0.574-0.733, P<0.001; ‘PTR’, HR=0.631, 95% CI 0.583-0.684, P<0.001).ConclusionsThis retrospective analysis demonstrated that combined PTR and metastasectomy or PTR alone were independent prognostic factors for survival improvement in gastric cancer patients with distant metastases. Because no statistically significant difference in survival was observed between the ‘PMTR’ group and ‘PTR’ group, PTR, which is a more minor surgery, might be more appropriate than PMTR in clinical practice for gastric cancer patients with distant metastases.

PurposePretreatment systemic inflammatory response has been confirmed to have prognostic value in patients with inoperable non-small-cell lung cancer (NSCLC). Increasing studies show that the modified Glasgow prognostic score (mGPS), a prognostic score based on C-reactive protein (CRP) and albumin, is a prognostic factor in these patients. This study was aimed at recognizing possible prognostic factors and new prognostic scores of inoperable NSCLC based on pretreatment systemic inflammatory response.Patients and methodsWe retrospectively reviewed the clinicopathological data of 105 patients with inoperable NSCLC who received first-line chemotherapy as initial treatment. Univariate and multivariate analyses of progression-free survival (PFS) and overall survival (OS) for prognostic factors and scores were performed.ResultsThe serum CRP, lactate dehydrogenase (LDH), cancer antigen 125 (CA125), and pathological type were independent pretreatment prognostic factors for PFS and OS. A new score was assembled by CRP, LDH, and CA125. In multivariate analysis, when the mGPS and the new score were covariates, only the new score retained independent prognostic value for both PFS (P<0.001; hazard ratio =2.12; 95% confidence interval: 1.60–2.82) and OS (P<0.001; hazard ratio =1.82; 95% confidence interval: 1.33–2.48).ConclusionThe new score based on pretreatment serum level of CRP, LDH, and CA125, indicates the prognosis of both PFS and OS in patients with inoperable NSCLC who were treated with first-line systemic chemotherapy, and it was found to be more effective than mGPS.