Hepatitis B virus reactivation and hepatitis in diffuse large B-cell lymphoma patients with resolved hepatitis B receiving rituximab-containing chemotherapy:risk factors and survival

Introduction:Hepatitis B virus(HBV) reactivation has been reported in B-cell lymphoma patients with resolved hepatitis B(hepatitis B surface antigen[HBsAg]-negative and hepatitis B core antibody[HBcAb]-positive).This study aimed to assess HBV reaaivation and hepatitis occurrence in diffuse large B-cell lymphoma(DLBCL) patients with resolved hepatitis B receiving rituximab-containing chemotherapy compared with HBsAg-negative/HBcAb-negative patients to identify risk factors for HBV reaaivation and hepatitis occurrence and to analyze whether HBV reaaivation and hepatitis affect the survival of DLBCL patients with resolved hepatitis B.Methods:We reviewed the clinical data of 278 patients with DLBCL treated with rituximab-containing therapy between January 2004 and May 2008 at Sun Yat-sen University Cancer Center,China.Prediaive faaors for HBV reaaivation,hepatitis development,and survival were examined by univariate analysis using the chi-square or Fisher's exact test and by multivariate analysis using the Cox regression model.Results:Among the 278 patients,165 were HBsAg-negative.Among these 165 patients,6(10.9%) of 55 HBcAb-positive(resolved HBV infeaion) patients experienced HBV reactivation compared with none(0%) of 110 HBcAb-negative patients(P=0.001).Patients with resolved hepatitis B had a higher hepatitis occurrence rate than HBsAg-negative/HBcAb-negative patients(21.8%vs.8.2%,P = 0.013).HBcAb positivity and elevated baseline alanine aminotransferase(ALT) levels were independent risk factors for hepatitis.Among the 55 patients with resolved hepatitis B,patients with elevated baseline serum ALT or aspartate aminotransferase(AST) levels were more likely to develop hepatitis than those with normal serum ALT or AST levels(P = 0.037,P = 0.005,respeaively).An elevated baseline AST level was an independent risk factor for hepatitis in these patients.Six patients with HBV reactivation recovered after immediate antiviral therapy,and chemotherapy was continued.HBcAb positivity,HBV reactivation,or hepatitis did not negatively affect the survival of DLBCL patients.Conclusions:DLBCL patients with resolved hepatitis B may have a higher risk of developing HBV reaaivation and hepatitis than HBsAg-negative/HBcAb-negative patients.Close monitoring and prompt antiviral therapy are required in these patients.

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.

A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is closely associated with high risk of nasopharyngeal carcinoma in Cantonese from southern China

Matrix metalloproteinase 2(MMP2) has been shown to play an important role in several steps of cancer development.The-1306C/T polymorphism of the MMP2 gene displays a strikingly lower promoter activity than the T allele,and the CC genotype in the MMP2 promoter has been reported to associate with the development of several cancers.To assess the contribution of the MMP2-1306C/T polymorphism to the risk of nasopharyngeal carcinoma(NPC),we conducted a case-control study and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched controls using real-time PCR-based TaqMan allele analysis.We found that subjects with the CC genotype had an increased risk(OR = 1.55,95% CI = 1.05-2.27) of developing NPC compared to those with the CT or TT genotypes.Furthermore,we found that the risk of NPC was markedly increased in subjects who were smokers(OR = 15.04,95% CI = 6.65-33.99),heavy smokers who smoked ≥20 pack-years(OR = 18.66,95% CI = 7.67-45.38),or young(<60 years) at diagnosis(OR = 1.52,95% CI = 1.01-2.29).Our results provide molecular epidemiological evidence that the MMP2-1306C/T promoter polymorphism is associated with NPC risk,and this association is especially noteworthy in heavy smokers.

Relationship between epidermal growth factor receptor gene mutation and copy number in Chinese patients with non-small cell lung cancer

Epidermal growth factor receptor(EGFR) gene mutation and copy number are useful predictive markers that guide the selection of non-small cell lung cancer(NSCLC) patients for EGFR-targeting therapy.This study aimed to investigate the correlation between EGFR gene mutation and copy number and clinicopathologic characteristics of Chinese patients with NSCLC.NSCLC specimens collected from 205 patients between November 2009 and January 2011 were selected to detect EGFR gene mutations with real-time polymerase chain reaction(RT-PCR) and to detect EGFR gene copy number with fluorescence in situ hybridization(FISH).EGFR mutations primarily occurred in females,non-smokers,and patients with adenocarinomas(all P < 0.001).Tissues from 128(62%) patients were FISH-positive for EGFR,including 37(18%) with gene amplification and 91(44%) with high polysomy.EGFR gene mutation was correlated with FISH-positive status(R = 0.340,P < 0.001).Multivariate analysis showed that not smoking(OR = 5.910,95% CI = 2.363-14.779,P < 0.001) and having adenocarcinoma(OR = 0.122,95% CI = 0.026-0.581,P = 0.008) were favorable factors for EGFR gene mutation.These results show a high frequency of EGFR FISH positivity in NSCLC tissues from Chinese patients and a significant relevance between EGFR gene mutations and FISH-positive status.Among the FISH-positive samples,EGFR gene mutation occurred more frequently in samples with gene amplification compared to those with high polysomy,suggesting that EGFR mutation and gene amplification should be used as clinical decision parameters to predict response to EGFR-targeting therapy.

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.

Germline mutational profile of Chinese patients under 70 years old with colorectal cancer

Background:Inherited susceptibility accounts for nearly one-third of colorectal cancer(CRC)predispositions and has an 80%-100%lifetime risk of this disease.However,there are few data about germline mutations of hereditary CRC-related genes in Chinese patients with CRC.This study aimed to assess the prevalence of gene mutations related to cancer susceptibility among Chinese patients with CRC,differences between Chinese and Western patients,and the phenotypegenotype correlation.Methods:We retrospectively collected tumor samples from 526 patients with CRC under 70 years old who underwent hereditary CRC genetic testing.A series of bioinformatic analyses,as well as statistical comparisons,were performed.Results:We found that 77 patients(14.6%)harbored functional variants of the 12 genes.The mutation frequencies of the top 5 mutated genes were 6.5%for MutL homolog 1(MLH1),5.1%for MutS homolog 2(MSH2),1.0%for MSH6,0.8%for PMS1 homolog 2(PMS2),and 0.8%for APC regulator of the WNT signaling pathway(APC).Our data showed much higher rates of mutations of MSH6 and PMS2 genes among all mismatch repair(MMR)genes as compared with those in Western populations.Mutations in MLH1,MSH2,and MSH6 were found to be mutually exclusive.Patients with MLH1 or MSH2 mutations had higher frequencies of personal history of cancer(MLH1:20.6%vs.8.7%;MSH2:25.9%vs.8.6%)and family history of cancer than those without these mutations(MLH1:73.5%vs.48.4%;MSH2:70.4%vs.48.9%),and the lesions were more prone to occur on the right side of the colon than on the left side(MLH1:73.5%vs.29.3%;MSH2:56.0%vs.31.0%).The proportion of stage I/II disease was higher in patients with MLH1 mutations than in those without MLH1 mutations(70.6%vs.50.7%),and the rate of polyps was higher in patients withAPC mutations than in those with wild-type APC(75.0%vs.17.4%).Conclusion:These results provide a full-scale landscape of hereditary susceptibility over 12 related genes in CRC patients and suggest that a comprehensive multi-gene panel testing for hereditary CRC predisposition could be a helpful analysis in clinical practice.