A new prognostic histopathologic classification of nasopharyngeal carcinoma

Background:The current World Health Organization(WHO) classification of nasopharyngeal carcinoma(NPC) con?veys little prognostic information.This study aimed to propose an NPC histopathologic classification that can poten?tially be used to predict prognosis and treatment response.Methods:We initially developed a histopathologic classification based on the morphologic traits and cell differentia?tion of tumors of 2716 NPC patients who were identified at Sun Yat?sen University Cancer Center(SYSUCC)(training cohort).Then,the proposed classification was applied to 1702 patients(retrospective validation cohort) from hospitals outside SYSUCC and 1613 patients(prospective validation cohort) from SYSUCC.The efficacy of radiochemotherapy and radiotherapy modalities was compared between the proposed subtypes.We used Cox proportional hazards models to estimate hazard ratios(HRs) with 95% confidence intervals(CI) for overall survival(OS).Results:The 5?year OS rates for all NPC patients who were diagnosed with epithelial carcinoma(EC;3708 patients),mixed sarcomatoid?epithelial carcinoma(MSEC;1247 patients),sarcomatoid carcinoma(SC;823 patients),and squamous cell carcinoma(SCC;253 patients) were 79.4%,70.5%,59.6%,and 42.6%,respectively(P < 0.001).In mul?tivariate models,patients with MSEC had a shorter OS than patients with EC(HR = 1.44,95% CI = 1.27–1.62),SC(HR = 2.00,95% CI = 1.76–2.28),or SCC(HR = 4.23,95% CI = 3.34–5.38).Radiochemotherapy significantly improved survival compared with radiotherapy alone for patients with EC(HR 49–0.75),and possibly for those with SCC(HR = 0.67,95% CI = 0.56–0.80),MSEC(HR = 0.58,95% CI = 0..74–1.28).= 0.63;95% CI = 0.40–0.98),but not for patients with SC(HR = 0.97,95% CI = 0Conclusions:The proposed classification offers more information for the prediction of NPC prognosis compared with the WHO classification and might be a valuable tool to guide treatment decisions for subtypes that are associ?ated with a poor prognosis.

ALK gene copy number gain and its clinical significance in hepatocellular carcinoma

AIM: To examine the status and clinical significance of anaplastic lymphoma kinase (ALK) gene alterations in hepatocellular carcinoma (HCC) patients.

Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations

Background:Identification of activated epidermal growth factor receptor(EGFR)mutations and application of EGFR-tyrosine kinase inhibitors(EGFR-TKIs)have greatly changed the therapeutic strategies of non-small-cell lung cancer(NSCLC).However,the long-term efficacy of EGFR-TKI therapy is limited due to the development of drug resistance.The aim of this study was to investigate the correlation between the aberrant alterations of 8 driver genes and the primary resistance to EGFR-TKIs in advanced NSCLC patients with activated EGFR mutations.Methods:We retrospectively reviewed the clinical data from 416 patients with stage III/IV or recurrent NSCLC who received an initial EGFR-TKI treatment,from April 2004 and March 2011,at the Sun Yat-sen University Cancer Center.Several genetic alterations associated with the efficacy of EGFR-TKIs,including the alterations in BIM,ALK,KRAS,PIK3CA,PTEN,MET,IGF1R,and ROS1,were detected by the routine clinical technologies.The progression-free survival(PFS)and overall survival(OS)were compared between different groups using Kaplan-Meier survival analysis with the log-rank test.A Cox regression model was used to estimate multivariable-adjusted hazard ratios(HRs)and their 95%confi-dence intervals(95%CIs)associated with the PFS and OS.Results:Among the investigated patients,169 NSCLC patients harbored EGFR-sensitive mutations.EGFR-mutant patients having PTEN deletion had a shorter PFS and OS than those with intact PTEN(P=0.003 for PFS,and P=0.034 for OS).In the combined molecular analysis of EGFR signaling pathway and resistance genes,we found that EGFR-mutant patients coexisted with aberrant alterations in EGFR signaling pathway and those having resistant genes had a statistically poorer PFS than those without such alterations(P<0.001).A Cox proportional regression model determined that PTEN deletion(HR=4.29,95%CI=1.72-10.70)and low PTEN expression(HR=1.96,95%CI=1.22-3.13),MET FISH+(HR=2.83,95%CI=1.37-5.86)were independent predictors for PFS in patients with EGFR-TKI treatment after adjustment for multiple factor.Conclusions:We determined that the coexistence of genetic alterations in cancer genes may explain primary resistance to EGFR-TKIs.