| ObjectiveThe purpose of our study is to explore the role of treatment-related markers PD-L1,PDL2,CD30 and CD23,GATA3,BCL-2,BCL-6,MUM1 in the diagnosis and prognosis evaluation of primary mediastinal B-cell lymphoma(PMBL),find more specific immunohistochemical indicators to improve the diagnosis of the disease,provide theoretical references for judging the prognosis of PMBL and guide individualized clinical treatment.MethodsA retrospective study was conducted on 34 patients diagnosed with PMBL in Chinese Academy of Medical Sciences Cancer Hospital from 2000 to 2019,and 31 patients with non-mediastinal primary diffuse large B-cell lymphoma(DLBCL-NOS)were used as control group.The expression of 8 proteins,including PD-L1,PD-L2,CD30 and CD23,GATA3,BCL-2,BCL-6 and MUM1,were detected by immunohistochemical(IHC)staining.We analyze the application value of these 8 proteins in the diagnosis and prognosis evaluation of PMBL.Results1.The median age of the PMBL group was 28 years old,while that of the control group was 63 years old.There was significant difference in age distribution between the two groups(P<0.001).Clinical symptoms of mediastinal compression are common in PMBL group,the tumor cells were diffusely distributed,segmented by slender or thick dense collagen and arranged in clusters,nests or nodules.The tumor cells are medium or slightly large,the cytoplasm is pale,and the nucleus is round or oval.In some cases,lymphoma cells have pleomorphism and/or lobulated nuclei,which may be similar to Reed-Sternberg cells.2.In terms of immunophenotype,the median percentages of PD-L1,PD-L2 and CD30 in PMBL group were 70%(30%,90%),25%(0,70%)and 17.5%(0,60%),respectively,which were significantly higher than the DLBCL-NOS group.The difference was statistically significant(P<0.05);the positive rates of CD30 and CD23 in PMBL group were 61.76%(21/34)and 76.47%(26/34),respectively,and the difference was statistically significant between the DLBCL-NOS group(P=0.000).However,there was no significant difference in the expression of GATA3(P=0.414),BCL-2(P=0.480),BCL-6(P=0.659)and MUM1(P=0.601)between PMBL and DLBCL-NOS groups(P>0.05).3.The survival curve of PMBL patients with CD30 and BCL-6 expression showed a trend of poor prognosis despite the P value>0.05.Conclusion1.PMBL is a mature and invasive large B-cell lymphoma originating from thymus with unique clinical characteristics and immunophenotype.2.The high expression levels of treatment-related markers PD-L1,PD-L2 and CD30 in PMBL are helpful to accurately identify more patients who may respond to immune or targeted therapy.Immunohistochemical staining of PD-L1,PD-L2,CD30 and CD23 is helpful for the differential diagnosis of PMBL and DLBCL-NOS.3.CD30 and BCL-6 show a certain trend in the prognosis of PMBL.As candidate prognostic indicators of PMBL,they should be further studied in a larger number of samples.ObjectiveIn order to provide useful information for the diagnosis and treatment of small cell lung cancer(SCLC)patients,we analyzed the relationship between the sequencing results,immunohistochemical expression and clinical data of 50 patients with SCLC.MethodsA retrospective study was conducted on 50 patients diagnosed with SCLC from 2010 to 2012 in Cancer Hospital of Chinese Academy of Medical Sciences.A targeted sequencing panel composed of 520 cancer-related genes was used to conduct genetic testing on the tumor samples of 50 patients with SCLC.The expression of TTF-1,CgA,CD56,CK18,Syn and Ki-67 proteins were detected by immunohistochemical staining,and the relationship between the sequencing results,immunohistochemical expression and clinical data was analyzed.Results1.The median age of the 50 patients with SCLC was 57 years old,of whom 36(72.0%)were male.Tirty-two patients(64.0%)were smokers,and 30 patients(60%)were central type.Eight patients(16%)were stage I,15 patients(30%)were stage II,and 24 patients(48%)were stage III.Eight patients(16%)received CE(carboplatin and VP-16)chemotherapy and 26 patients(52%)received EP(cisplatin and VP-16)chemotherapy;Twelve patients(24%)received radiotherapy.One patient received a preventive cranial irradiation(PCI).2.The most common mutant genes in this study were TP53(N=47,94.0%),RB1(N=43,86.0%),LRP1B(N=22,44.0%),SPTA1(N=13,26.0%)and KMT2D(N=12,24.0%).Compared with the Cologne and MSKCC two white cohorts,NOTCH2,JAK2 and CDK12 have higher mutation frequency in Chinese SCLC(P<0.05).The single nucleotide variation(SNV)was dominated by C>A,accounting for 34.1%of the total SNV.3.The median TMB for the entire study population was 10.3 muts/Mb.TMB-H(≥10.3muts/Mb)in Chinese SCLC patients was significantly associated with ATM(P=0.023),CREBBP(P=0.010),KMT2D(P=0.050)and LRP1B(P=0.000)gene mutations.4.Syn expression is associated with mutations in four signaling pathways(cGMP-PKG,Chemokine,TGF-β,and PhosphoLipase D),and CgA with mutations in two signaling pathways(cGMP-PKG and PhosphoDylinositol).5.Kaplan-Meier curves showed that age<55 years(P=0.017),mutant ARID2(P=0.055),and high TMB(P=0.035)were associated with better prognosis,and patients with mutations in the RAS signaling pathway had significantly better prognosis(P=0.022).High TMB was an independent prognostic factor in SCLC patients(HR=0.251,95%CI:0.070-0.901,P=0.034).In a combined enlarged cohort with the previous two studies,survival analysis showed that SCLC patients with mutant LRP1B showed a longer overall survival(OS)(P=0.0017);Patients with high TMB(≥7 muts/MB)in the combined cohort had better outcomes(P=0.0053),which is consistent with our findings in the Chinese cohort.Conclusion1.The mutation spectrum of Chinese SCLC patients is different from that of Caucasians.2.The immunophenotypic characteristics of Syn and CgA of SCLC are related to the abundant gene mutations in the signaling pathway.3.Among SCLC patients,mutant LRP1B and gene mutations in the Ras pathways are associated with better prognosis,and high TMB is an independent prognostic factor for SCLC patients. |
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