The Clinical Characteristics And Molecular Prognostic Analysis Of Patients With Primary Gastric Non-Hodgkin Lymphoma

The gastrointestinal tract is the most common extranodal presentation site of primary extranodal non-Hodgkin lymphomas(NHL),with 10% to 15% of all NHL cases and30%-50% of extranodal NHL located here.The most commonly involved sites are the stomach(47% to 74%),the small bowel,followed by(in decreasing order of frequency)the terminal ileum,jejunum and duodenum and finally the colon.The esophagus is rarely affected.All pathological types in nodal lymphoma can occur in extranodal lymphoma.Diffuse large B-cell Lymphoma(DLBCL)(47%)and mucosa-associated lymphoid tissue(MALT)Lymphoma(24%)are more frequently represented in gastric.Primary gastric(PG)MALT Lymphoma and DLBCL account for the majority of gastric tumors after adenocarcinoma.Due to the heterogeneity,diagnosis and treatment for lymphoma become complicated.The prognosis is quite different.Accurate prognostic judgment is curcial to the selection of therapeutic regimen.Besides the clinical characteristics,a series of molecular prognostic markers has been introduced to better describe this clinical entity.Such as,according to tumor cells: Large B-cell lymphomas with MYC plus BCL2 and/or BCL6 rearrangements is an adverse prognosis factors of DLBCL.Currently,there is growing interest in the use of MYC and other immunohistochemistry either to help screen for DHL/THL or to identify “double-expressor”(DE)large B-cell lymphomas.As to the tumor microenvironment the cellular composition of the tumor microenvironment has also been shown to be a powerful predictor of survival in patients with DLBCL.Lenz et al performed GEP on a large series of DLBCL patients and defined 2 important stromal signatures,stromal-1 and stromal-2.The stromal-1 signature reflects extracellular matrix deposition and histiocyte infiltration,and portends a good prognosis.The stromal-2signature largely reflects angiogenesis and blood vessel density in the tumor stroma,and portends a poor prognosis.In this thesis,we will analyzed clinical and biological prognostic factors in PG-DLBCL and MALT lymphoma.Part ? The clinical characteristics and molecular prognostic analysis of 138 patients with primary gastric diffuse large B cell lymphomaObjective: To analyze the clinical characteristics and molecular prognostic of the patients with primary gastric diffuse large B cell lymphoma(PG-DLBCL).Methods: 138 patients with PG-DLBCL were retrospectively assayed and followed up,the age,gender,LDH,?2-MG,B-symptom,ascities,mass,ECOG score,Helicobaeter pylori(Hp)infection,international prognostic index(IPI)score,Lugano staging,infiltration of bone marrow,method of treatment were analyzed.Pathological data were analyzed by using interphase fluorescence in situ hybridization(FISH)technique and immunohistochemistry technology(IHC).CD10,MUM-1,BCL-2,BCL-6,c-MYC,Ki-67,CD31,SPARC protein expressions were analyzed by IHC,and abnormal c-MYC,BCL-2,BCL-6 genes were examined by FISH.IBM SPSS22 statistical software was used to perform chi-square or Mann-Whitney U test,life table survival analyses,Cox proportional hazards model.Categorical data were expressed as percentages(n %).Continuous data were expressed as median(inter-quantile range).Results: 138 patients with primary gastric diffuse large B cell lymphoma(DLBCL)were enrolled,including 66(47.8%)males and 34(52.2%)females.Male to female ratio is0.92:1.The median age was 55(17-85)years.The median survival time was 40(1-140)months.The 3-year,5-year overall survival(OS)rate were 79.1%,75.3% respectively.The number of CD10,MUM-1,BCL-2,BCL-6,MYC,CD31,SPARC protein positive cases were 43(31.2%),62(44.9%),82(59.4%),71(51.4%),27(19.6%),67(48.6%),60(43.5%)respectively.According to Hans model,GCB subgroup accounted for 51(36.9%)cases,and non-GCB subgroup 63(63%)cases.The number of abnormal gene of MYC was 20(14.5%,12 cases with multiple copies,8 cases with rearrangement),and the number of abnormal gene of BCL-2 was 23(16.7%,22 cases with multiple copies,11 cases with rearrangement),while the number of abnormal gene of BCL-6 was 33(23.9%,12 cases with multiple copies,11 case with rearrangement).No one has the coexistence of MYC and BCL-2 or/and BCL-6 genes abnormities.There was no statistical significance of overall survival rates between normal and abnormal genes subgroup.The overall survival rates of normal and abnormal MYC gene,BCL-2 genes,BCL-6 genes,were 65.5% and 63.6%(p=0.848),64.6% and 62.4%(p=0.698),63.9% and 65%(P=0.979)respectively.According to IHC,univariaten analysis showed that “double expression”(MYC protein express?40% +BCL-2 protein express?50%),non-GCB subgroup were adverse prognostic factors,while CD31 protein express<10% + SPARC protein express?5% was an benifical prognostic factor.COX risk model regression analysis revealed that age,IPI score,Hans model, “double expression” were independently adverse prognostic factors.CD31 protein express< 10% + SPARC protein express?5% was an benificial prognostic factor.Rituximab therapy based on chemotherapy could improve outcome.Conclusion: “double expression” were independently adverse prognostic factors in PG-DLBCL patients.CD31 protein express<10% + SPARC protein express?5% was an beneficial prognostic factor.Age,IPI score,Hans model were independent prognostic factors.Rituximab therapy based on chemotherapy could improve outcome.Part ? The clinical characteristics and prognostic analysis of 50 patients with gastric mucosa-associated lymphoid tissue lymphomaObjective: To analyze the clinical characteristics and prognostic of the patients with gastric mucosa-associated lymphoid tissue lymphoma.Methods: The clinical data of 50 MALT lymphoma patients treated from February2004 to March 2015 in our hospital were retrospectively analyzed.Results: Among 50 patients,24 cases were females,26 cases were males.Male to female ratio is 1.08:1.The average age was 52.3 years,the median age was 56 years(18 ~78 years).Helicobaeter pylori(Hp)was detected in 38 patients(76%).The median survival time was 70 months(1-141 months).The 5-year os rate was 80.1%.There was no significant difference in 5-year OS between the patients in surgery group and non-surgery group(P = 0.710).Chemotherapy has significant influence on the survival prognosis.There was statistical difference in OS between the chemotherapy groups and non-chemotherapy group(P = 0.004).Lugano staging system can effectively evaluate patient's disease states,chi square test showed,according to Lugano staging system,patients in advanced stages(IIE-IV)was older and the LDH level,ECOG score,IPI score were higher when compared with patients in early stages(I/II).Univariaten analysis revealed that age,ECOG,Lugano staging,IPI score,and chemotherapy were correlated with OS.Multivariate analysis showed that higher IPI score(IPI 3-5)was independent prognostic factors for OS.Conclusion: The primary gastric MALT Lymphoma patients usually had low risk IPI and achieved longterm survival.Frontline therapy for lowrisk patients was radiotherapy or Hp eradication,and chemotherapy for high-risk ones.The surgical resection haven?t improve the OS of the patients,while non-surgical treatment can avoid the surgical trauma and improve the quality of life.The prognostic analysis showed that IPI score was independent factors for OS.