1.Expression and clinical significance of HPV16/18, p16, Her-2 in squamous cell cervical carcinoma
Lei BAO ; Suhong LI ; Quanhong WANG ; Wei BAI ; Ruifang SUN
Cancer Research and Clinic 2012;24(5):304-307
Objective To study the expression of HPV、p16 and Her-2 in the squamous cell cervical carcinoma and its chnical significance. Methods Expression of HPV16/18、p16, and C-erbB-2 and the amplification of Her-2 gene were examined using situ hybridization technique,SP immunohistochemistry,and FISH imaging analysis system in 60 cases of cervical cancer, 61 cases of CIN, and 21 cases of normal cervical tissue,respectively.Results The positive rates of HPV16/18 and p16 in the normal tissue,CIN Ⅰ -Ⅱ,CINⅢ and the squamous cell cervical carcinoma were gradually increased, they wereo (0/21),9.68 % (3/31),46.67 % (14/30),71.67 % (43/60);0 (0/21),19.35 % (6/31),93.33 % (28/30),96.67 % (58/60),respectively,and there were significant differences among the groups (P<0.05),but no significant difference was found between the normal tissue and the CIN Ⅰ - Ⅱ. The positive rates of Her-2 and Her-2 in the CIN Ⅲ and the carcinoma were 13.33 % (4/30),31.67 % (19/60),3.33 % (1/30),21.67 % (13/60),respectively,but in the normal group and the CIN Ⅰ - Ⅱ wereo,and the differences between the carcinoma group and the CIN group,the carcinoma group and the normal group were significant(P<0.05).The expression of Her-2 and the amplification of Her-2 were closely related to the stage, degree of differentiation and metastasis of lymph node in the squamous cell cervical carcinoma (P<0.05). Conclusion The infection of HPV is one of thetriggers for the squamous cell cervical carcinoma.The expression of p16 and the amplification of Her-2 may be closely correlated with tumor development and high expression of p16 and Her-2 indicates poor prognosis.
2.The relationship between expression of Her-2 and human papillomavirus and clinicopathological features in esophageal and stomach multiple primary cancers
Xialin ZHANG ; Jianmin LI ; Ruifang SUN ; Wei BAI
Cancer Research and Clinic 2015;(9):597-601
Objective To analyze the relationship between expression of Her-2 protein and the infection of human papillomavirus (HPV) and clinicopathological features in upper gastrointestinal multiple primary cancers, and to explore the relationship between the different histological malignancies in a single-system. Methods 39 patients were primary esophageal squamous cell carcinoma and gastric/cardia adenocarcinoma. By using immunohistochemistry (IHC) methods, the expression of Her-2 protein in 39 cases of multiple primary cancers specimens were examined, and by using insitu hybridization (ISH) technology, the infection of HPV in the same ones were detected. Results The over-expression of Her-2 protein in esophageal squamous cell carcinoma was not significantly relative to the degree of differentiation, the depth of penetration, the lymph node metastasis and the patientsˊage and gender (P> 0.05). The over-expression of Her-2 protein in gastric adenocarcinoma was closely correlated to the invasion depth and lymph node metastasis (P<0.05), no obvious correlation with the factors of patientsˊage and gender and the degree of differentiation (P > 0.05). The infection of HPV in esophageal squamous cell carcinoma and gastric adenocarcinoma was not significantly relative to the degree of differentiation, the depth of penetration,the lymph node metastasis, and the age and gender of the patients (P> 0.05). In the upper gastrointestinal multiple primary cancers, the Her-2 protein over-expression had the consistency (κ= 0.56, P< 0.05). Meanwhile, the HPV-DNA expression also had the consistency (κ=0.80, P<0.05). Conclusion Both Her-2 protein and HPV expression show the consistency in upper gastrointestinal multiple primary cancers,which suggests that Her-2 protein and HPV may be the common oncogenic factors for both esophageal squamous cell carcinoma and gastric adenocarcinoma.
3.The investigation of expression of CD95, CD44V6 in breast cancer and lymph node micrometastasis
Lixia WANG ; Li LI ; Suhong LI ; Ruifang SUN ; Wei BAI ; Quanhong WANG
Cancer Research and Clinic 2009;21(4):248-250
Objective To investigate the relationship and clinicopathologic significance between the expression of CD95,CD44V6 and metastasis of axillary lymph node in breast cancer.Methods Immunohistochemistry was used to detect the expression of CD95 and CD44V6 in 101 cases of breast cancer, in which, 40 cases without metastasis in axillary lymph node were detected MCK expression by IHC. The results were analyzed statistically. Results 9 cases of breast cancer with lymph node micrometastasis were observed by IHC in 40 cases without metastasis in axillary lymph node by microscope. The expression of CD95, CD44V6 in lymph node metastasis group was similar as in lymph node micrometastasis group. There was significant difference of CD95 expression between those with lymph node metastasis and those without. The positive rate of CD95 and the high expression of CD44V6 in the cases that the tumor size was over 2 cm were significandy higher than in the cases that the tumor size was less than 2 cm (P<0.05). Conclusion Detection of the expression of CD95, CD44V6 in breast cancer may be helpful to predict the lymph node micrometastasis and provide more dependable evidence for judging prognosis and selecting treatment prescription clinically.
4.Expression of apoptosis inhibitor Survivin and apoptosis protease Caspase-3 in uterine smooth muscle tumour
Jing WANG ; Jianmin LI ; Wei BAI ; Ruifang SUN ; Lingxian CHEN ; Haiyan DU ; Peng BU
Cancer Research and Clinic 2009;21(4):245-247
Objective To study the expression of Survivin and Caspase-3 in uterine smooth muscle tumour (USMT) and it' s significance. Methods Expression of Survivin and Caspase-3 protein were determined by immunohistochemistry Two-step method on 30 uterine Cellular Uterine Leiomyoma (CUL), 10 normal uterine smooth muscle (NSM), 10 Ordinary Uterine Leiomyoma (OUL), 15 Leiomysarcoma (LMS). Results Survivin level in normal uterine smooth muscle are very low, and in OUL, CUL, LMS was on increasing trend, the OL group and the LCA group have statistical significant difference(P<0.05). Caspase-3 level in NSM, OUL, CUL, LMS was on decreasing trend. The NSM group and the CL group, the NSM group and the LCA group both have statistical significant difference (P<0.05). Conclusion Maybe Survivin can inhibit apoptosis and extend cells lives by inhibit the activity of Caspase-3, so it played an important role in the development progress from benign uterine tumour to malignant uterine tumour. The detect of Survivin and Caspase-3 may be useful in the differential diagnosis of uterine smooth muscle tumours.
5.Significance of Choi's and Hans's classification of DLBCL in the clinical prognosis
He LI ; Jinfen WANG ; Yanfeng XI ; Ruifang SUN ; Wei BAI ; Jing LI
Journal of Leukemia & Lymphoma 2011;20(5):292-295,299
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.
6.Clinical significance of HER-2 protien overexpression and HER-2 gene dysregulation in non-small cell lung cancer
Xiaogang WANG ; Zhenwen CHEN ; Yanfeng XI ; Fei CHAI ; Yirong XU ; Jing LI ; Ruifang SUN ; Wei BAI
Cancer Research and Clinic 2016;28(1):21-27
Objective To investigate the dysregulation of HER-2 protein and gene in non-small cell lung cancer (NSCLC), and to identify the association between clinicopathological features,prognosis and HER-2 aberrations amongst protein and gene. Methods 140 NSCLC tissues (89 squamous cell carcinoma, 51 adenocarcinoma) with operative section and detailed case were taken from pathology department of Shanxi Cancer Hospital from Jan 2006 to Feb 2007, while 70 normal tissues were set as control group. Immunohistochemistry was applied to detect the state of HER-2 protein expression,and fluorescence in situ hybridization (FISH) was applied to test the status of gene amplification. Results In normal and NSCLC tissues, over-expression of HER-2 was detected in 0 case and 17 (12.14 %) cases (P < 0.05), respectively. The over-expression of HER-2 was associated with the pathological type of NSCLC, which was detected more frequently in adenocarcinoma (χ2 = 4.19, P = 0.04), rather than the gender, age, smoke history, clinical stages, and lymphatic metastasis of patients. 40 (28.57 %) cases presented HER-2 gene copy number ≥3, including 6 (4.29 %) patients with HER-2 gene amplification, 34 (24.29 %) patients with HER-2 gene multicopy. HER-2 gene amplification was associated with the pathological type (P = 0.024), smoke history (P = 0.048) and age (P = 0.015), rather than lymphatic, gender, clinical stages. None clinicopathological features were presented correlation with HER-2 gene multicopy (P > 0.05). There was no significantly difference in survival between patients with and without HER-2 protein over-expression and HER-2 gene dysregulation (P > 0.05). HER-2 protein over-expression was associated with HER-2 gene amplification (P > 0.05), while no relationship between HER-2 protein overexpression and HER-2 gene multicopy (P < 0.01). Conclusions The over-expression of HER-2 is related to pathological type of NSCLC with more frequent expression in adenocarcinoma. The incidence rate of HER-2 gene amplification in patients with adenocarcinoma histology, never-smokers, and young age is high. The HER-2 protein over-expression and gene dysregulation show no relation with the prognosis of NSCLC.
7.Expression of c-myc in anaplastic large cell lymphoma and its significance
Fei CHAI ; Zhenwen CHEN ; Yanfeng XI ; Ruifang SUN ; Wei BAI ; Jing LI ; Yirong XU
Journal of Leukemia & Lymphoma 2015;24(4):238-244
Objective To investigate the protein expression and genetic alterations of c-myc in primary systemic anaplastic large cell lymphoma (ALCL) and discuss its relationship with clinicopathologic features and immunophenotypes.Methods 87 cases of ALCL were selected.Immunohistochemical method was used to detect the protein expression of c-myc,ALK,CD3,CD10,CD20,CD30 and EMA.c-myc and ALK genetic alterations were detected by using fluorescence in situ hybridization (FlSH).The interrelationships between protein expression,genetic alterations and clinicopathological parameters were analysed statistically.Results Immunohistochemical results:of 87 cases,ALK protein was expressed in 54 cases (62.1%).c-myc protein was expressed in 27 cases (31.0 %).ALK and c-myc were co-expressed in 20 cases (23.0 %).c-myc protein expression,ALK and c-myc co-expression increased with the upgrade of ALCL clinical stages,and the expression was higher in International Prognostic Index (IPI) high-risk groups than in low-risk groups (P < 0.05).FISH test results:of 87 ALCL cases,there were 50 cases (57.5 %) of ALK rearrangements and 19 cases (21.8 %) of ALK aneuploidy.c-myc rearrangement was detected in none of 87 ALCL cases,but there was aneuploidy in 19 cases (21.8 %).The differences of c-myc aneuploidy in ALK positive and negative groups were statistically insignificant (P > 0.05),while they were statistically significant in c-myc groups (P < 0.05) and in different IPI groups (P < 0.05).Conclusion c-myc protein expression and aneuploidy were related with ALCL clinical stages and IPI,which could be used as an indicator of estimating ALCL malignant degree and predicting prognosis.
8.Expression of CD68, cyclin D1 and rearrangement of bcl-6 gene are adverse prognostic factors in diffuse large B-cell lymphoma
Xiaojie LIANG ; Jinfen WANG ; Wei BAI ; Ruifang SUN
Chinese Journal of Pathology 2015;(8):559-564
Objective 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).Methods Gets paraffin samples of the 105 cases DLBCL with the detailed follow-up information , and were studied by using immunohistochemical EnVision method for CD 3, 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.Results 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 stageⅠ-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 CD 68 contrast alloimmune phenotype groups had a poor prognosis,non-GCB type with high expression of cyclin D 1 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 CD 68, cyclin D1 ( P <0.05 ), the R-CHOP treatment, there was no statistically significant difference between CD 68, 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.Conclusions 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 .
9.Significance of C-myc expression in T-lymphoblastic lymphoma/leukemia and its relation with prognosis
Yanhua ZHANG ; Jing LI ; Yanfeng XI ; Wenqi BAI ; Wei BAI ; Ruifang SUN
Chinese Journal of Pathology 2015;(8):571-577
Objective To study the C-myc gene and protein in T lymphoblastic lymphoma/leukemia ( T-LBL/ALL) and its relationship to prognosis.Methods 60 cases of T-LBL/ALL with follow-up data were studied by using immunohistochemical EnVision method for CD 1a, CD3,εCD3, CD7, CD10, CD34, CD43,CD45RO,CD99,TDT,CD20,CD23,MPO,Ki-67 and C-myc.20 cases of reactive lymph nodes were selected as normal control group of C-myc gene and protein.Fluorescence in-situ hybridization ( FISH) for C-myc gene ( located on chromosome8q24 ) was performed to detect its breakage and gain.Results Among the 60 cases of T-LBL/ALL, immunohistochemistry results showed:the percentages of tumor cells expression of CD1a, CD3, εCD3, CD7, CD10, CD34, CD43, CD45RO, CD99and TDT were 38.3%(23/60), 75.0%(45/60), 45.0%(27/60),95.0%(57/60),36.7%(22/60),23.3%(14/60), 60.0%(36/60),41.7%(25/60),96.7%(58/60)and 93.3%(56/60).Separately, while CD20 ,CD23 and MPO were all negative.A figure of Ki-67 expression≤80% was found in 36 cases and >80% was found in 24 cases.The positive rate of C-myc protein was 66.7%(40/60) in 60 cases of T-LBL/ALL,was 0%(0/20) in 20 cases of reactivated lymphoid tissue (χ2 =26.67,P<0.05).C-myc protein expression was positively correlated with the mediatinal width and Ki-67 index ( P <0.05 ).Fluorescence in-situ hybridization results showed that among the 60 cases of T-LBL/ALL, C-myc gene with breakage of 8q24 was detected in 6 cases ( 10.0%) , and gains in 11 cases ( 18.3%).20 cases of reactive lymph nodes were not occurred breakage and gains of C-myc gene .It is not significant between C-myc gene and protein expression (P>0.05).In addition, in 60 cases of T-LBL/ALL, 12(20.0%) cases of C-myc protein and genetic abnormalities coexist.Log-rank analysis results: The prognosis of C-myc protein positive group was worse than negative group ( P<0.05 ).The relationship of C-myc gene and prognosis was not significant ( P>0.05).C-myc protein and genetic abnormality coexist is related with worse prognosis ( P<0.05 ).COX analysis results show that the C-myc protein positive group may be a independent poor prognosis factors ( P<0.05).Conclusions C-myc may play an important role on the development of T-LBL/ALL.It may be a independent prognosis factors .
10.Protective effect of brain derived neurotrophic factor on mesenchymal stem cells when transplanting to the surrounding issue of intracerebral hemorrhage stove
Ruifang REN ; Liangguo HUANG ; Minglu HUANG ; Guohong JIANG ; Jie BAI
Chinese Journal of Neuromedicine 2014;13(3):252-256
Objective To observe the migration ofmesenchymal stem cells (MSCs) transfected with recombinant lentiviral vectors carried brain derived neurotrophic factor (BDNF) gene from lateral ventricle to intracerebral hemorrhage stove in rats and to discuss the protective effect of BDNF on MSCs.Methods Intracerebral hemorrhagic models were constructed in 60 SD rats and randomly divided into 4 groups:phosphate buffer solution (PBS) group,BMSCs group,BMSCs-enhanced green fluorescent protein (EGFP) group and BMSCs-EGFP-BDNF group (n=15); PBS,BMSCs,lentiviral vector (LV)carried EGFP and LV carried BDNF-EGFP were,respectively,injected into the lateral cerebral ventricle of each group; 7,14 and 21 d after the injection,BDNF protein expression in the BMSCs of each group was detected by Western blotting and immunofluorescence; the migration of BMSCs from lateral ventricle to intracerebral hemorrhage stove was observed by signal labeling immunofluorescent staining.Results Western blotting and immunofluorescence showed that the BDNF protein expression in the MSCs-EGFP-BDNF group was significantly higher than that in the MSCs group and MSCs-EGFP group (P<0.05); signal labeling immunofluorescent staining of brain tissue section indicated that the MSCs-EGFP-BDNF group had significantly larger number of BMSCs-positive cells which migrated to the surrounding issues of intracerebral hemorrhage stove than MSCs group and MSCs-EGFP group (P<0.05),while there were no significant differences between the latter two except on the 7th d of establishment of models.Conclusion BMSCs modified with recombinant LV carried BDNF gene have high expression level of BDNF,indicating that BDNF performs a protective effect on BMSCs.