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Objective:To investigate the expression of enhancer of zeste homolog 2 (EZH2) and its relationship with clinicopathological characteristics and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The clinicopathological data of 106 DLBCL patients with detailed follow-up data in Shanxi Provincial Cancer Hospital from January 2009 to December 2018 were retrospectively analyzed, including 30 cases (28%) of germinal center B cell-1ike (GCB) and 76 cases (72%) of non-GCB; and 11 cases of reactive lymph nodes were selected as the control group. EnVision method was used to detect the expressions of EZH2 and c-myc. The correlation of the expressions of EZH2 and c-myc proteins was analyzed, and the association of EZH2 protein with clinicopathological characteristics, overall survival (OS) and progression-free survival (PFS) of patients was also analyzed.Results:The positive expression rates of EZH2 and c-myc proteins were 78.3% (83/106) and 48.1% (51/106), respectively, and neither was expressed in the control group. The positive expression rate of EZH2 protein in non-GCB was higher than that in GCB ( P < 0.01). The expression of EZH2 was correlated with clinical staging, serum lactic dehydrogenase (LDH) level and international prognostic index (IPI) score (all P < 0.01). EZH2 expression was positively correlated with the c-myc protein expression in GCB ( r = 0.74, P < 0.001). Moreover, OS and PFS of EZH2 negative in DLBCL were better than those of EZH2 positive (all P < 0.001). Conclusions:EZH2 overexpression is correlated with advanced clinical staging, increased serum LDH level, high IPI score and non-GCB phenotype. The high expression of EZH2 may be related to the high expression of c-myc, suggesting the poor prognosis of patients with DLBCL.
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Due to the special structure of lymphoid tissues and the heterogeneity of lymphocytes, the classification of lymphoma is complex, and the diagnosis of lymphoma has always been one of the difficulties in pathological diagnosis. For more than half a century, the pathological diagnosis of lymphoma in China has developed rapidly with the international development of discipline, especially after the 1970s, with the development of immunology and molecular biology, the pathological diagnosis and classification of lymphoma are becoming more and more perfect, and it has become a model for pathology to promote the development of clinical medicine.
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Objective To investigate the expressions of programmed death-ligand 1 (PD-L1) and PD-L2 and phosphorylated protein kinase B (p-AKT) in diffuse large B-cell lymphoma (DLBCL) patients and their correlations with clinicopathological features and prognosis. Methods A total of 68 paraffin-embedded specimens of DLBCL patients diagnosed in Shanxi Provincial Cancer Hospital with detailed follow-up record from January 2010 to December 2012 were included in the study. The expressions of PD-L1, PD-L2 and p-AKT proteins in DLBCL were detected by using immunohistochemistry (IHC). Results The positive rate of PD-L1 protein in DLBCL patients was 22.1％ (15/68), which was related to germinal center B-cell (GCB) subtype or not (χ2= 5.591, P= 0.018), clinical stage (χ2= 3.969, P= 0.046), international prognostic index (IPI) grades (χ2=4.178, P=0.041) and treatment remission rate (χ2=6.587, P=0.010). The positive rate of PD-L2 protein in DLBCL patients was 14.7％ (10/68), which was related to extranodal metastasis or not (χ2=6.772, P= 0.009). The positive rate of p-AKT for DLBCL patients was 61.8％ (42/68), which was correlated with age (≥60 years old) or not (χ2=6.227, P=0.013), Eastern Cooperative Oncology Group (ECOG) grades (χ2=4.005, P=0.045), B symptoms (χ2=10.187, P=0.001) and treatment remission rate (χ2=4.096, P=0.043). Univariate survival analysis showed that the overall survival (OS) rate and progression free survival (PFS) rate of PD-L1 protein positive expression group were lower than those of PD-L1 protein negative expression group (both P< 0.05). In the patients with non-GCB subtype, OS rate and PFS rate of PD-L1 protein positive expression group were lower than those of PD-L1 protein negative expression group (both P<0.05). p-AKT protein positive expression group had poorer OS rate and PFS rate compared to p-AKT negative expression group (both P< 0.05). Correlation analysis showed that PD-L1 protein expression was correlated with PD-L2 and p-AKT proteins expressions (r= 0.380, P= 0.001;r= 0.273, P= 0.025). The prognosis was worse when p-AKT and PD-L1 proteins was co-expressed (P< 0.05). Multivariate analysis suggested high expressions of PD-L1 and p-AKT proteins were independent prognosis risk factors in DLBCL (both P<0.05). Conclusions The expressions of PD-L1 and p-AKT proteins may be involved in the occurrence and development of DLBCL. Blocking PD-1 and PD-L1 access or combined blocking could provide a promising future for the clinical therapy.
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Objective@#To investigate the relationship of PD-L1 protein expression and gene amplification in gastric cancer and their correlation with clinicopathologic factors.@*Methods@#The cohort included 247 gastric cancer specimens with follow-up data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD-L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).@*Results@#PD-L1 protein was expressed in 25.9% (64/247) of the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC). There was a correlation between the two (P<0.01). The expression of PD-L1 in tumor cells correlated with the degree of differentiation and tumor diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0% (47/247), and was associated with age, large/small curvature of the stomach, tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting that the coincidence of IHC and FISH was poor (P=0.157). There was a negative correlation between PD-L1 protein expression on tumor cells and prognosis in gastric cancer. There was no significant correlation between PD-L1 protein expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression analysis showed that PD-L1 protein expression, depth of invasion and lymph node metastasis were all independent prognostic risk factors for gastric cancer.@*Conclusions@#Concordance between PD-L1 protein expression and gene amplification is poor. PD-L1 protein expression may signify poor prognosis. There is no significant correlation between PD-L1 gene amplification and prognosis of patients with gastric cancer.
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Objective To study the values of clinicopathological features and expression of thyroid transcription factor 1 (TTF-1) in predicting the mutation status of epidermal growth factor receptor (EGFR) gene in patients with non-small cell lung cancer (NSCLC). Methods Mutation status of exons 18, 19, 20 and 21 in EGFR, and expression of TTF-1 protein in 283 cases of NSCLC diagnosed in Shanxi Provincial Cancer Hospital from January 2013 to December 2014 were analyzed by using amplification refractory mutation system (ARMS) and immunohistochemical method. The correlation of EGFR mutations with the clinicopathological features and TTF-1 expression were studied to explore the values of them in the prediction of EGFR mutations. Results Among 283 cases of NSCLC, the rate of EGFR gene mutation was 30.0 ％(85/283), including 3 cases with double mutations(exon 18 and exon 20 double mutations in one case, exon 19 and exon 21 double mutations in one case, exon 20 and exon 21 double mutations in one case). The EGFR gene mutations were associated with gender, histological type, history of smoking, and expression of TTF-1 (all P<0.001), but not related to age and tumor location (P= 0.785, P= 0.138). The combination of factors with high mutation rates (women, adenocarcinoma, no smoking, and TTF-1 positive) made the positive predictive value of EGFR mutations up to 57.6 ％. And the combination of factors with low mutation rates (male, nonadenocarcinoma, smoking history, TTF-1 negative) made the EGFR negative predictive value up to 90.3％. Conclusion The combination of clinicopathological features and TTF-1 expression status in patients with NSCLC has a great predictive value for EGFR mutations, which can provide a useful reference for clinical treatment decision-making.
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Objective To detect C-met protein expression and gene amplification in lung adenocarcinoma, and to analyze their relationship with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) resistance and prognosis. Methods A total of 120 cases of lung adenocarcinoma diagnosed in Shanxi Provincial Cancer Hospital from January 2011 to May 2013 were selected. The expressions of C-met protein and C-met gene amplification were conducted by immunohistochemistry (IHC) method and fluorescence in situ hybridization (FISH), and all patients were followed up. The relationship between the expression of C-met protein and gene amplification with clinicopathological features and EGFR-TKI resistance and prognosis were analyzed. Results The high expression of C-met protein and gene amplification in 120 tissues were 17.5 ％ (21/120), 10.83 ％ (13/120). Of the 80 patients treated with EGFR-TKI, the incidence of C-met protein high expression was 30.43 ％ (14/46) in patients with drug resistance, which was significantly higher than that in patients without drug resistance (11.76 ％, 4/34), the difference was statistically significant (χ2= 3.908, P= 0.048). The rate of C-met gene amplification was 19.57 ％ (9/46) in patients with drug resistance,which was significantly higher than that in patients without drug resistance (2.94 ％, 1/34) the difference was statistically significant (P= 0.038). The expression of C-met protein in 46 patients with drug resistance was positively correlated with gene amplification (r= 0.388, P= 0.008), but in 40 patients without TKI, the expression of C-met protein was not correlated with gene amplification (r=0.279, P=0.081). The high expression of C-met protein was correlated with age, pathological grade and clinical stage (all P<0.05), while C-met gene amplification was related to clinical stage (P=0.036). Cox regression analysis suggested that C-met gene amplification was an independent prognostic factor (P= 0.034). Conclusions C-met protein expression and gene amplification are risk factors for EGFR-TKI resistance. C-met gene amplification suggests poor prognosis, and can be used as an independent factor for prognostic evaluation.
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Objective To explore the relationship between myc/bcl-2 and myc/p53 co-expression and the prognosis of diffuse large B-cell lymphoma (DLBCL). Methods A total of 148 DLBCL cases with the follow-up data in Shanxi Cancer Hospital from January 2010 to October 2014 were selected. The expression of myc, bcl-2 and p53 protein in paraffin samples was detected by immunohistochemistry (IHC). Results The positive expression rate of myc, bcl-2 and p53 was 35.1 % (52/148), 60.1 % (89/148) and 24.3 % (36/148) respectively in 148 patients with DLBCL. There were 37 (25.0%) cases of myc/bcl-2 co-expression, which were correlated with Hans classification (χ2= 4.749, P= 0.029), IPI score (χ2= 4.894, P= 0.027), bone marrow invasion (χ2= 4.751, P= 0.029), and efficacy evaluation (χ2= 9.14, P= 0.003). Myc/p53 co-expression was detected in 17 cases (11.5 %), which was associated with Hans classification (χ2 = 5.349, P= 0.021) andLDH level (χ2= 11.1, P= 0.001). Univariate analysis revealed that myc [overall survival (OS): χ2= 6.044, P= 0.014; progression free survival (PFS):χ2= 6.212, P= 0.013], bcl-2 (OS:χ2= 5.812, P= 0.016; PFS:χ2= 4.878, P= 0.027), p53 (OS:χ2= 20.092, P< 0.0001; PFS:χ2= 18.492, P< 0.0001), myc/bcl-2 co-expression (OS: χ2= 11.277, P= 0.001; PFS:χ2= 9.024, P= 0.003) and myc/p53 co-expression (OS: χ2=21.150, P< 0.0001; PFS: χ2 = 18.655, P< 0.0001) were the adverse prognostic factors. In addition, the survival rate of the co-expression group was lower than that of single expression group, and the survival rate of myc/p53 co-expression group was lower than that of myc/bcl-2 co-expression group. Multivariate analysis showed that among the six independent variables, including myc, bcl-2, p53, myc/bcl-2, myc/p53 and treatment regimen, p53 expression was an independent prognostic affecting factor of OS (95%CI 0.172ˉ0.763, P=0.008) and PFS (95%CI 0.172ˉ0.773, P=0.009). Conclusion Myc, bcl-2 and p53 are the poor prognostic factors in DLBCL. Myc/bcl-2 and myc/p53 co-expression have synergistic effect, indicating the poor prognosis.
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There have been many changes of the lymphoma classifications from early times till the 2016 WHO classifications. The 2016 WHO lymphoma classification aims to provide updated diagnostic categories, more precise diagnostic criteria, and biological and clinic correlates, which can facilitate state-of-the-art patient care, future therapeutic advances and basic research in this field.
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Objective To investigate the epidermal growth factor receptor (EGFR),KRAS and BRAF mutations and their correlation with clinicopathological characteristics in non-small-cell lung cancer (NSCLC).Methods The mutations of exon 18,exon 19,exon 20 and exon 21 of the EGFR,codon 12,codon 13 of the KRAS and codon 600 of the BRAF gene in 143 cases of NSCLC were detected by gene sequencing.The relationship between the mutations and clinicopathological features was analyzed by SPSS 16.0.Results EGFR mutation was detected in 57 cases (39.9 ％),including 2 mutations in exon 18,25 in exon 19,3 in exon 20,24 in exon 21 and 3 multiple point mutations.KRAS mutation was found in 25 cases (17.5 ％),including 23 in codon 12 and 2 in codon 13.BRAF V600E mutation was detected only in 2 cases (1.4 ％).No patient harboring multiple EGFR,KRAS and BRAF mutations was found.EGFR mutation rate was related to gender,smoking history,histological types,differentiation and tumor size (P ＜ 0.05).However,no relationship was found among lymph node metastasis,pTNM stage and EGFR mutation (P ＞ 0.05).There was no association between KRAS mutation and clinicopathological features including gender,smoking history,histological types,differentiation,tumor size,lymph node metastasis and pTNM stage (P ＞ 0.05).Conclusions The frequency of EGFR mutation in NSCLC is high,and usually occurs in female,non-smokers,smaller tumors,better differentiation and adenocarcinomas.The frequency of KRAS mutation is not associated with the clinicolpathological features.The frequency of BRAF mutation is very low,and EGFR,KRAS and BRAF gene mutations do not occur at the same time.These results contribute to the target therapy of NSCLC.
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Objective To investigate the expression of mutant p53,Ki-67,ER and PR in uterine endometrial carcinoma and uterine serous carcinoma,and explore their significance in differential diagnosis.Methods The samples including 37 cases of uterine endometrial carcinoma and 37 cases of uterine serous carcinoma were analyzed.The expression of mutant p53,Ki-67,estrogen receptor and progesterone receptor were performed by using the immunocytochemical (IHC) EnVision system.Data were analyzed with SPSS 11.5 statistic software.Results The positive rate of mutant p53 in uterine endometrial carcinoma was statistically lower than that in uterine serous carcinoma [21.62 ％ (8/37) vs 64.86 ％ (24/37) (P ＜ 0.01)].The positive rate of Ki-67 in uterine endometrial carcinoma was statistically lower than that in uterine serous carcinoma [37.84 ％ (14/37) vs 70.27 ％ (24/37) (P ＜ 0.01)].The positive rate of estrogen receptor in uterine endometrial carcinoma was statistically higher than that in uterine serous carcinoma [78.38 ％ (29/37) vs 32.43 ％ (12/37) (P ＜ 0.01)].The positive rate of progesterone receptor in uterine endometrial carcinoma was statistically higher than that in uterine serous carcinoma [75.67 ％ (28/37) vs 29.73 ％ (11/37) (P ＜ 0.01)].Conclusions The expression of mutant p53 and Ki-67 are higher in uterine serous carcinoma.The expression of estrogen receptor and progesterone receptor are higher in uterine endometrial carcinoma.Combined detection of mutant p53,Ki-67,ER and PR has important significance in screening and preventing uterine endometrial carcinoma and uterine serous carcinoma.
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Objective To investigate the distribution characteristics of the Epstein-Barr virus (EBV)in lymphomas.Methods 438 cases of lymphomas were reclassified according to the WHO classification of lymphoma (2008).ALK1,CD3,CD5,CD7,CD10,CD15,CD20,CD23,CD30,CD43,CD56,CD68,CD79,CD99,CyclinD1,EMA,IgD,TdT,Vs38C and LMP-1 were detected by in situ hybridization of EBER and immunohistochemistry.Results In B cell lymphoma,T and NK cell lymphoma and Hodgkin' s lymphoma (HL),the positive rates of EBER were 5.4 ％ (14/261),16.5 ％ (19/115) and 59.7 ％ (37/62),respectively,and the positive rates of LMP-1 were 5.4 ％ (14/261),5.2 ％ (6/115) and 59.7 ％ (37/62).In DLBCL patients,EBER expression in the older group was significantly higher than that in the younger one [13.2 ％ (7/53) vs 1.2 ％ (1/81),P ＜ 0.05].The expression of EBER and LMP-1 were inconsistent in T and NK cell lymphomas,and the positive rate of EBER was significantly higher than that of LMP-1 (P ＜ 0.05).EBER was all positive in 5 cases of NK/T cell lymphoma-nasal type.The expression of EBER and LMP-1 were consistent in HL.Conclusion The EBV infection was associated with the classification of the lymphoma.The EBV infection was the highest in NK/T cell lymphoma-nasal type,and the next was in HL.Due to the consistency of EBER and LMP-1 expression in the HL,economically,LMP-1 may replace EBER as the indicator of EBV.EBV might play an important role in the occurrence and development of NK/T cell lymphoma-nasal type,HL and so on.
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<p><b>OBJECTIVE</b>To study expression of CD68, cyclin D1 protein and rearrangement of bcl-6 gene impact on the prognosis of diffuse large B-cell lymphoma (DLBCL).</p><p><b>METHODS</b>Gets paraffin samples of the 105 cases DLBCL with the detailed follow-up information, and were studied by using immunohistochemical EnVision method for CD3, CD10, CD20, CD68, cyclin D1, bcl-6, MUM 1, SOX-11 immunolabeling. The DLBCL were classified into germinal center B cell-like (GCB) subtypes and non-germinal center B cell-like (non-GCB) subtypes according to Hans'algorithm. Application of fluorescence in situ hybridization (FISH) technique to detect the bcl-6 gene rearrangement. The relationship between CD68, cyclin D1 protein, the bcl-6 gene and the curative effect of chemotherapy and survival was analyzed using statistical software. Respectively by GCB type, non-GCB type immune phenotype and CHOP, R-CHOP chemotherapy group, compare the curative effects.</p><p><b>RESULTS</b>105 patients had GCB 19 cases (18.1%), non-GCB 86 cases (81.9%), CD68 expression was 18 cases (17.1%), cyclin D1 high expression 36 cases (34.3%), bcl-6 gene rearrangement in 21 cases (21.9%), there is no correlation among the three (P > 0.05). One-way analysis of variance showed that age ≤ 60 years, clinical stage I-II, IPI score 0 to 2 points, LDH (U/L) < 245 IU/L,GCB subtypes, R-CHOP therapy, the prognosis of patients with better (P < 0.05), But gender, primary site no correlation with prognosis (P > 0.05). CD68, cyclin D1 high expression, bcl-6 rearrangement had poor prognosis (P < 0.05). Stratification analysis results show GCB-type or non-GCB type with high expression of CD68 contrast alloimmune phenotype groups had a poor prognosis, non-GCB type with high expression of cyclin D1 and rearrangement of bcl-6 gene had a poor prognosis (P < 0.001, P = 0.02). Treatment scheme of layered display, the CHOP treatment, significantly correlated with overall survival with high expression of CD68, cyclin D1 (P < 0.05), the R-CHOP treatment, there was no statistically significant difference between CD68, cyclin D1 high expression and overall survival (P = 0.428 and 0.168). Multivariate COX model analysis showed that high expression of CD68 (P = 0.026), high expression of cyclin D1 (P = 0.003) and high levels of LDH (P = 0.005) were adverse prognostic factors independent.</p><p><b>CONCLUSIONS</b>high expression of CD68, cyclin D1 and rearrangement of bcl-6 gene suggests poor prognosis, CD68, cyclin D1 protein and bcl-6 gene can be used as a prognostic indicator in patients with DLBCL.</p>
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Humans , Antibodies, Monoclonal, Murine-Derived , Antigens, CD , Metabolism , Antigens, Differentiation, Myelomonocytic , Metabolism , Antineoplastic Combined Chemotherapy Protocols , B-Lymphocytes , Classification , Cyclin D1 , Metabolism , Cyclophosphamide , DNA-Binding Proteins , Genetics , Doxorubicin , Gene Rearrangement , Germinal Center , Cell Biology , In Situ Hybridization, Fluorescence , Lymphoma, Large B-Cell, Diffuse , Diagnosis , Prednisone , Prognosis , Proto-Oncogene Proteins c-bcl-6 , VincristineABSTRACT
Objective To study the expression of miR-320d in diffuse large B cell lymphoma (DLBCL),and its correlation with prognosis of DLBCL.Methods Sixty cases of DLBCL with the follow-up data were collected from Shanxi Cancer Hospital,and were examined by immunohistochemical EnVision method for CD3,CD10,CD20,bcl-6 and Mum-1.The DLBCL were classified into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subtypes according to Hans' algorithm.Agilent Human miRNA Microarray 16.0 was used to select the miRNAs on 24 cases paraffin-embedded tissue of DLBCL.The expression levels of miR-320d in 62 cases were examined by TaqMan real-time polymerase chain reaction.Eleven cases of reactive hyperplasia of lymph node were selected as control.Results In 62 cases of DLBCL,22 cases (35.5 ％) were GCB and 40 cases (64.5 ％) were non-GCB subtypes.The expression of miR-320d in GCB was 3.43 times as much as non-GCB subtypes (P =0.034),and in reactive hyperplasia of lymph node it was 5.65 times as much as in DLBCL (P ＜ 0.001).The low expression groups of miR-320d was significantly correlated with shorter overall survival (P =0.021).Multivariate Cox proportional hazard regression analysis (including the IPI scores) revealed that the down-regulated miR-320d was the independent predictor in DLBCL (RR =2.434,95 ％ CI 1.148-5.159,P =0.020).Conclusions The down-regulated expression of miR-320d might be considered as a distinct subgroup with poor prognosis.
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<p><b>OBJECTIVE</b>To compare the application values of real-time quantitative PCR-Sanger sequencing and TaqMan probe method in the detection of KRAS and BRAF mutations, and to correlate KRAS/BRAF mutations with the clinicopathological characteristics in colorectal carcinomas.</p><p><b>METHODS</b>Genomic DNA of the tumor cells was extracted from formalin fixed paraffin embedded (FFPE) tissue samples of 344 colorectal carcinomas by microdissection. Real-time quantitative PCR-Sanger sequencing and TaqMan probe method were performed to detect the KRAS/BRAF mutations. The frequency and types of KRAS/BRAF mutations, clinicopathological characteristics and survival time were analyzed.</p><p><b>RESULTS</b>KRAS mutations were detected in 39.8% (137/344) and 38.7% (133/344) of 344 colorectal carcinomas by using real-time quantitative PCR-Sanger sequencing and TaqMan probe method, respectively. BRAF mutation was detected in 4.7% (16/344) and 4.1% (14/344), respectively. There was no significant correlation between the two methods. The frequency of the KRAS mutation in female was higher than that in male (P < 0.05). The frequency of the BRAF mutation in colon was higher than that in rectum. The frequency of the BRAF mutation in stage III-IV cases was higher than that in stageI-II cases. The frequency of the BRAF mutation in signet ring cell carcinoma was higher than that in mucinous carcinoma and nonspecific adenocarcinoma had the lowest mutation rate. The frequency of the BRAF mutation in grade III cases was higher than that in grade II cases (P < 0.05). The overall concordance for the two methods of KRAS/BRAF mutation detection was 98.8% (kappa = 0.976). There was statistic significance between BRAF and KRAS mutations for the survival time of colorectal carcinomas (P = 0.039). There were no statistic significance between BRAF mutation type and BRAF/KRAS wild type (P = 0.058).</p><p><b>CONCLUSIONS</b>(1) Compared with real-time quantitative PCR-Sanger sequencing, TaqMan probe method is better with regard to handling time, efficiency, repeatability, cost and equipment. (2) The frequency of the KRAS mutation is correlated with gender. BRAF mutation is correlated with primary tumor site, TNM stage, histological types and histological grades.(3) BRAF gene mutation is an independent prognostic marker for colorectal carcinomas.</p>
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Genetics , Pathology , Adenocarcinoma, Mucinous , Genetics , Pathology , Carcinoma, Signet Ring Cell , Genetics , Pathology , Colonic Neoplasms , Genetics , Pathology , Colorectal Neoplasms , Genetics , Pathology , DNA Mutational Analysis , Mutation , Neoplasm Grading , Neoplasm Staging , Oligonucleotide Probes , Proto-Oncogene Proteins , Genetics , Proto-Oncogene Proteins B-raf , Genetics , Proto-Oncogene Proteins p21(ras) , Real-Time Polymerase Chain Reaction , Rectal Neoplasms , Genetics , Pathology , Sequence Analysis, DNA , Sex Factors , ras Proteins , GeneticsABSTRACT
Objective To detect the correlation of immunophenotyping of DLBCL with Choi's and Han' s classification to the prognos is. Methods Ninty-nine cases of DLBCL were studied using immunohistochemistry EnVision method for bcl-6, CD10, FOXP1, GCET1, MUM1 in Shanxi cancer hospital. The follow-up was included. All cases they were classified according to Hans' s and Choi' s algorithm. Fluorescence in situ hybridization (FISH) for bcl-6 gene expression (located on chromosome 3q27) was performed on paraffin-embedded tissues of 35 cases. Results In Hans classification, 21 cases were GCB and 78 were nonGCB subtype. In Choi's classification, 23 cases were GCB and 76 cases were nonGCB subtype. According to the both classification, the prognosis in GCB group was much better than that in nonGCB's (P = 0.000). The expression of FOXP1 was inverse proportion to the prognosis (P =0.011), on the contrary GCET1 expression was in proportion to the prognosis (P =0.027). Among all of 35 DLBCL cases, bcl-6 rearrangement was more frequently encountered in the nonGCB type, bcl-6 gene rearrangement was no correlated to bcl-6 protein expression. Conclusion On the basis of classification, GCB group had a better clinical outcome than that of nonGCB group. FOXP1, GCET1, bcl-6 protein expression is associated with different outcome in DLBCL. Both of Choi's and Hans's algorithm play an important role in the immunophenotyping and prognosis.
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Objective To investigate the significance and expression of PTEN, MLL in T lymphoblastic lymphoma/leukaemia(T-LBL/ALL). Methods Seventy-six cases of T-LBL/ALL were studied by using immunohistochemical EnVision method for PTEN. Fluorescence in-situ hybridization (FISH) for MLL gene (located on chromosome 11q23) was performed to detect its breakage and amplification. Results Among the 76 cases ofT- LBL/ALL, the positive rate of PTEN was 64.47 % (49/76), lower than that in reactivated lymphoid tissue (100 %, 20/20) (λ2= 19.220, P ＜0.05). PTEN expression was reversely correlated to theclinical stage, Ki-67 index and LDH level (P ＜0.05). Among the 76 cases, MLL gene with breakage of 11q23 was detected in 13 cases (17.11%), and amplification in 18 cases (23.68 %). Survival rate ot MLL gene breakage group was lower than that of non-breakage group (25.0 %, 43.6 %). Survival rate of MLL gene amplification group was lower than that of non-amplification group too (17.1%, 42.7 %). Both of breakage and amplification were related to prognosis ( λ 2 = 11.357, λ 2 = 4.533; P ＜0.05). Conclusion Anti-oncogene PTEN down-regulation may play an important role on the development and proceeding of T-LBL/ALL. MLL gene with breakage and amplification of 11q23 are helpful to predict prognosis of T-LBL/ALL. The case with MLL gene breakage and amplification of T-LBL/ALL may have a poor prognosis. It hints this group maybe a subtype of T-LBL/ALL.
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Objective To investigate the genetic changes of FGR and TP73 in PTCL-NOS, in order to verify the results of our previous a-CGH study and to explore their role on the pathogenesis of PTCL-NOS. Methods A total of 34 cases, of which 19 cases were examined by a-CGH, were investigated by interphasedual-colour FISH using homemade site-specific probes of FGR and TP73 by using a labelling method of nick translation and commercial probe CEP1. Results In general, 7 of 34 (20.6 %) cases of PTCL-NOS showed genetic aberrations, of which 4 cases had changes on both of the loci of FGR and TP73, including 3 cases of amplification and 1 loss of heterozygosity (LOH), 1 case of FGR amplification and other 2 TP73 amplification only. CEP1 amplification was detected in 4 cases (11.8 %), simultaneously associated with FGR/ TP73 gene amplification. Kaplan-Meier survival analysis indicated there was a trend that the group with genetic changes had a poorer prognosis than the group of non-genetic changes, and so as the group of TP73 genetic changes compared with the group of TP73 non-genetic changes, although their was no statistical significance (P >0.05). Conclusion The outcome of this study partially verified the results of a-CGH, and aberration of lymphoma-related genes FGR and TP73, and the amplification of CEP1 may play a significant role in the pathogenesis of PTCL-NOS.
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Objective To study the expression of PTEN et al and their significance in T lymphoblastic lymphoma/leukaemia (T-LBL/ALL). Methods Seventy-six cases of T-LBL/ALL were studied by using immunohistochemistry (EnVision method) for CD3, CD7, CD10, CD20, CD23, CD43, CD45RO, CD99, TdT, MPO and PTEN. Follow-up was included. Results In the Seventy-six cases of T-LBL/ALL, the percentages of tumor cells expressing TdT, CD99, CD3, CD7, CD45RO and CD43 were 93.42%, 94.74%, 67.12%, 92.11%, 36.85%,and 51.33%, respectivly while MPO, CD20 and CD23 were all negative. The index of Ki-67 expression higher than 80 % was found in 27 and ≤80% in 49 cases. The expression of PTEN (64.47 %) in T-LBL/ALL was lower than that of in reactivated lymphoid tissue (100%, P0.05). Conclusion The antibodies of CD3,CD7, CD10, CD20, CD43, CD45RO, CD99, TdT, MPO and Ki-67 were very helpful for the diagnosis of T-LBL/ALL.Down-regulation of PTEN may play an important role on the development of T-LBL/ALL.
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Objective To analyze the genetic changes in peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and to find the key molecular aberrations underlying its pathogenesis. Methods A total of 37 cases of PTCL-NOS were investigated by 1Mb resolution array comparative genomic hybridisation (Array-CGH), in which 9 cases were further studied by using a Tile path array-CGH. DNA extraction, clonality analysis and histologic review were conducted to exclude 6 cases with polyploidy and without obvious genetic imbalances from this study. Results In general, there was a considerable overlap in the CGH profiles in many PTCL-NOS cases. The most recurrent regions of genomic gains were lp36.13-1p36.32, 7q22.1, 7q36.1-7q36.3, 7q32.1-7q32.3, 7q22.1-7q34,9p11 .2-9q12 and 9q33.3-9q34.3. The most recurrent regions of genomic losses were 1p12-1p21.1 and 13q14.11-13q14.3. Conclusion Genomic gains and losses are frequently identified in PTCL-NOS with array-CGH, in which patients with multiple chromosomal alterations (≥6regions) have poor prognosis. These genomic profiles are broadly important to reveal a distinct subgroup with genetic alterations and to find the key genomic imbalance of PTCL-NOS.
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Objective To investigate the expressions and clinicopathological significance of 3q27-3q29-related p63 protein in diffuse large B-cell lymphoma (DLBCL). Methods An immunohistochemical Envision~(TM) method was used to detect the expressions of p53 and 3q27-3q29-related p63 protein in 102 cases of DLBCL and 15 cases of reactive hyperplasia of lymph node (RHL). Results The tumor cell expressions of p53(62 %) and p63(56 %) in DLBCL were significantly higher than that in RHL (0 and 13 % P < 0.05). The expressions of p53 and p63 were significantly different (1) between stage Ⅰ + Ⅱ (the positive rate 48.3 % and 41.4 %, respectively) and stage Ⅲ+Ⅳ(the positive rate 79.5 % and 75 %, respectively; P <0.05), (2) between GCB type (the positive rate 28 % and 28 %, respectively) and non-GCB type(the positive rate 72.7 % and 64.9 %, respectively; P <0.05). The expressions of p53 and p63 had no relationship to gender, age, B symptoms and locations. The expression of p53 was positively correlated with that of p63 in DLBCL (P <0.05, Cp=0.629). p53 and p63 protein expression in negative group the 5-year overall survival rate is higher than that in positive group (38 % and 6 %, 51% and 4 %, respectively), the difference was statistically significant (P <0.05). Conclusion It was likely that p63, as the oncogene, participated in the occurrence and development of DLBCL together with p53. Also, p63 and p53 might play a synergistic role in the occurrence DLBCL. Combined detection of 3q27-3q29-related 1963 protein and p53 protein in DLBCL, might be one of the indicators to the prognosis of DLBCL.