β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及意义

Objective To explore the expression of p-catenin,Glut-1,PTEN in uterine endometrioid adenocarcinoma and their roles in tumorigenesis.Methods A total of 83 cases of endometrial hyperplasia were selected and reclassified according to EIN diagnostic criteria.Expressions of p-catenin,Glut-1 and PTEN proteins were investigated by immunohistochemistry in 10 proliferative endometrium,83 endometrial hyperplasia and 24 endometrioid adenocarcinoma.Results(1)24 EIN(28.9%)lesions were reclassified among 83 previously diagnosed endometrial hyperplasia,of which,16 of 24 EIN cases(66.7%)had a prior diagnosis of complex atypical hyperplasia The relation between EIN diagnosis and grade of atypical hyperplasia was not obvious(P＞0.05).(2)Normal(membranous)expression of p-catenin was present in 10 cases of proliferative endometrium.Abnormal(marked membranous/cytoplasmic,cytoplasmic and/or nuclear or negative)expression rates of p-catenin in EIN lesions(50%,12/24)and endometrioid adenocarcinoma(66.1%,16/24)were significantly higher than that of benign hyperplasia(10.2%,6/59)respectively(P＜0.01).However,the difference was not significant between EIN lesions and endometrioid adenocarcinomas(P＞0.05).(3)Low level expressions of Glut-1 was present in proliferative endometrium and benign hyperplasia.Overexpression of Glut-1 was present in 58.3%(14/24)of EIN and 70.8% (17/24)of endometrioid adenocarcinoma,respectively,and statistically not significant(P＞0.05).(4)Percentages of loss of PTEN expression showed no difference between EIN lesions(37.5%,9/24)and proliferative endometrium(2/10),benign hyperplasia(28.8%,17/59),endometrioid adenocarcinoma (62.5%,15/24;P＞0.05).However,loss of PTEN expression in endometrioid adenocarcinoma was significantly higher than those in proliferative endometrium and benign hyperplasia(P＜0.05).Conclusions Abnormal expression of p-catenin and overexpression of Glut-1 may be the early events in tumorigenesis of endometrioid adenocarcinoma.The expression of both markers may be useful in distinguishing a benign hyperplasia from EIN and endometrioid adenocarcinoma.Lack of PTEN expression may be the earliest event in endometrial carcinogenesis.However,it can not be used yet as a diagnostic marker for the EIN lesioa     

伴微乳头状分化的胃肠道腺癌的临床病理学特征和免疫组织化学研究

Objective To study the clinicopathologic features and immunophenotype of gastrointestinal adenocarcinomas with a micropapillary pattern differentiation(GAMPD). Methods Seventy-three eases of GAMPD arising in gastrointestinal tract were retrospectively reviewed.Immunohistochemical study for epithelial membrane antigen(EMA), insulin-like growth factorⅡmRNAbinding protein-3(IMP3)and E-cadherin was performed.Results Amongst the 73 cases studied,the micropapillary pattern accounted for 5% to 70% of the tumor component.It was often seen in a background of moderately differentiated adenocarcinoma.As compared with conventional adenocarcinoma,nodal metastasis was more frequently observed and the TNM tumor stage was statistically higher in GAMPD.The occurrence of micropapillary component in metastatic lymph nodes positively correlated with the proportion of mieropapillary pattern in primary lesions.EMA staining on the stroma-facing surface of tumor micropapillae was demonstrated in 52.1%(38/73)of the cases.As compared with EMA-negative GAMPD, EMA-positive GAMPD was more in the stomach(P=0.018).and with more metastatic lymph nodes(6.6 4-5.8 vs 3.8 ±4.7, P=0.029).The rate of IMP3 expression in EMA-positive GAMPD was 86.8%(33/38),which was higher than that in conventional adenocarcinoma.In contrast.the rate of E-cadherin expression in GAMPD was lower than that in conventional adenocarcinoma.Conclusions GAMPD is a distinctive variant of gastrointestinal adenocarcinomas and different from conventional adenocarcinoma in tumor morphology.immunophenotype and biologic behavior.It carries an aggressive clinical course and poor prognostic outcome.Immunohistochemical study for EMA.IMP3 and E-cadherin would be helpful in the diagnosis and prognostic evaluation of GAMPD.     

Estrogen regulates osteogenic differentiation of human periodontal ligament stem cells via Wnt/beta-catenin signaling pathway北大核心

BACKGROUND: Estrogen can promote the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs), but the molecular mechanism is unclear. OBJECTIVE: To study the regulatory effect of estrogen on the osteogenic differentiation of hPDLSCs via Wnt/β-catenin signaling pathway. METHODS: The hPDLSCs were isolated and purified by digestion method combined with limited dilution clone method. Three experimental groups were set as follows: osteogenic induction only (control group); 1×10-7 mol/L estrogen with osteogenic induction (estrogen group); and 100 µg/L Wnt3a protein with osteogenic induction (Wnt3a group). Alkaline phosphatase activity was detected at 1, 3, 5, 7 days of osteogenic induction. Western blot was used to detect the expression of Wnt/β-catenin signaling pathway related proteins β-catenin, P-GSK-3β, GSK-3β, CyclinD1 and osteoblast-related proteins Runx2 and OCN after 7 days of osteogenic induction. RESULTS AND CONCLUSION: The activity of ALP in all groups increased with time. The expression level of ALP in the estrogen group and Wnt3a group was higher than that in the control group at 1, 3, 5 and 7 days of induction (P < 0.05), while there was no significant difference between the former two groups (P > 0.05). The western blot results showed that the expression levels of β-catenin, P-GSK-3β, CyclinD1, Runx2 and OCN in the estrogen group and Wnt3a group were higher than those in the control group (P < 0.05), while the expression of GSK-3β was lower than that in the control group (P < 0.05). But there were no differences in the expression of Wnt/β-catenin signaling pathway related proteins and mid-late osteogenic markers between estrogen group and Wnt3a group (P > 0.05). To conclude, estrogen can enhance the osteogenic differentiation of hPDLSCs, and the underlying mechanism is likely to activate the Wnt/β-catenin signaling pathway in activated hPDLSCs exposed to estrogen. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Microrna-520a-3p induces apoptosis in lung cancer stem cells via modulation of map3k2北大核心

BACKGROUND: Studies have confirmed that microRNA (miR)-520a-3p has a regulatory role in lung cancer stem cells, but the specific function and mechanism of action are still unknown. OBJECTIVE: To investigate the influence of miR-520a-3p on the apoptosis of lung cancer stem cells, and to explore the underlying mechanism. METHODS: The magnetic activated cell sorting method was utilized to separate the CD133+ lung cancer stem cells from the lung cancer A549 cell line. The expression of miR-520a-3p in the lung cancer stem cells was determined by the real-time PCR assay. Liposome transfection assay was used to up-regulate the miR-520a-3p expression level in the lung cancer stem cells, and flow cytometry assay was applied to detect the influence of miR-520a-3p expression on the apoptosis of the lung cancer stem cells. Moreover, the modulation of MAP3K2 gene by the miR-520a-3p was analyzed by the dual-luciferase reporter gene assay, and the influence of miR-520a-3p expression on the protein expression of MAP3K2, Bcl-2 and Caspase-3 was analyzed by western blot assay. RESULTS AND CONCLUSION: The real-time PCR showed that the expression level of miR-520a-3p in CD133+ lung cancer stem cells was significantly lower than that in the CD133- lung cancer cells (P < 0.05). Overexpression of miR-520a-3p significantly increased the apoptotic rate of CD133+ lung cancer stem cells (P < 0.05). The dual-luciferase reporter gene assay results suggested that inhibition of miRNA-520a-3p could increase the luciferase activity of the reporter plasmids containing the 3’-untranslated region (3’-UTR) of MAP3K2 gene (P < 0.05), and overexpression of miR-520a-3p could decrease the luciferase activity of the reporter plasmids containing the 3’-UTR of MAP3K2 gene (P < 0.05). Moreover, miR-520a-3p overexpression also decreased the protein levels of MAP3K2 and Bcl-2 in the CD133+ lung cancer stem cells, P < 0.05), and increased the Caspase-3 protein level (P < 0.05). To conclude, in the lung cancer stem cells, miR-520a-3p was in a low-expressed status. miR-520a-3p could inhibit the expression of MAP3K2 gene, thereby inducing the cell apoptosis. Subject headings: Lung Neoplasms; Neoplastic Stem Cells; MAP Kinase Kinase Kinase 2; Apoptosis; Tissue Engineering. © 2018, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

乳腺癌和乳腺导管内增生性病变Notch1基因甲基化的检测及临床意义

Objective To explore the relevance between the promoter methylation status of Notch1gene and the invasive ductal carcinoma and ductal hyperplastic lesions of the breast.Methods Methylation status of Notch1 gene in human breast invasive ductal carcinoma(IDC,n=89),ductal carcinoma in situ (DOS,n=20),atypical ductal hyperplasia(ADH,,n=11)and usual ductal hyperplasia(UDH,n=20)were quantitatively evaluated by MALDI-TOF MS.The expression of Notch1 protein was detected by immunohistochemical stain(SP method).Results Positive expression rates of Notch1 protein in IDC and DCIS were 91.0%(81/89)and 75.0%(15/20),respectively,which were significandy higller than those 0f ADH(4/11)and UDH(30.0%.6/20;P＜0.05).Notch1 protein expression was correlated significantly with lymph node metastasis,pathological grades and TNM stages of IDC.The mean methylation levels of Notch1 gene at CpG_3,CpC 4.5 and CpG_8 significantly decreased in IDC group compared with those of DCIS.ADH and UDH groups(P＜0.0083).In breast carcinomas, the mean methylation rates of Notch1 gene at CpG-4.5,CpG-10.11,and CpG_14.15.16 loci in cases with axillary node metastasis were significantly lower than those without axillary node metastasis(P＜0.05):and the methylation rates at CpG_14.15.16 and CpG_18 lociin stage Ⅰ were lower than that in stage Ⅱ,further lower than that in stage Ⅲ(P＜0.05);and that in CpG_1.2,CpG_12.13 loci in grade Ⅰ(highly-differentiated group)were higher than that in grade Ⅱ(moderate-differentiated group)and grade Ⅲ(peody-differentiated group) (P＜0.05);and the methylation rates at CpG_3,CpG_8 and CpG_14.15.16 loci in ER+ PR+ HER2-group were lower than that in ER-PR-HER2+ group(P＜0.05).Conclusions There is an overall hypomethylation of Notch1 gene in breast invasive ductal carcinomas with corresponding over-expression of Notehl protein.This inverse correlation show that the alteration of protein expression result from hypomethylation oncogene Notch1,and this change may have important significance in breast tumorigenesis and the development.Specific hypomethylation at CpG_3,CpG_4.5 and CpG_8 loci of Notehl gene may play a role in the pathogenesis of breast carcinoma,suggesting the progression and/or malignant transformation from benign glandular lesions of the breast.     

伴微乳头状分化的胃肠道腺癌的临床病理学特征和免疫组织化学研究

目的 探讨伴微乳头状分化的胃肠道腺癌(GAMPD)的临床病理特征及上皮细胞膜抗原(EMA)、胰岛素样生长因子Ⅱ mRNA结合蛋白-3(IMP3)和E-cadherin表达的临床意义.方法 对73例GAMPD进行临床病理学分析,并应用免疫组织化学EnVision法检测EMA、IMP3和E-cadherin 在GAMPD中的表达.结果 在73例GAMPD中,微乳头状癌分化成分所占比例为5%～70%,多见于中分化腺癌.与普通腺癌比较,GAMPD在转移阳性淋巴结和TNM分期上存在明显差异.淋巴结转移性微乳头状癌成分与原发灶微乳头状癌成分含量呈正相关.微乳头状癌细胞簇间质面EMA表达阳性率为52.1%(38/73).EMA+组好发于胃(P=0.018),EMA+ 组阳性淋巴结平均数量为(6.6±5.8)枚,多于EMA-组(3.8±4.7)枚,两组差异具有统计学意义(P=0.029),其余临床病理学参数EMA+组与EMA-组比较差异无统计学意义.IMP3在EMA+组GAMPD中的表达阳性率为86.8%(33/38),显著高于普通腺癌(P＜0.05).而E-cadherin在GAMPD中的阳性表达率则显著低于普通腺癌(P＜0.00).结论 GAMPD是一种在组织学形态、免疫表型和生物学行为上不同于胃肠道普通腺癌的特殊类型,侵袭性强、预后差.免疫组织化学联合检测EMA、E-cadherin和IMP3的表达对GAMPD的病理诊断和预测预后有帮助.

Abstract：

Objective To study the clinicopathologic features and immunophenotype of gastrointestinal adenocarcinomas with a micropapillary pattern differentiation(GAMPD). Methods Seventy-three eases of GAMPD arising in gastrointestinal tract were retrospectively reviewed.Immunohistochemical study for epithelial membrane antigen(EMA), insulin-like growth factorⅡmRNAbinding protein-3(IMP3)and E-cadherin was performed.Results Amongst the 73 cases studied,the micropapillary pattern accounted for 5% to 70% of the tumor component.It was often seen in a background of moderately differentiated adenocarcinoma.As compared with conventional adenocarcinoma,nodal metastasis was more frequently observed and the TNM tumor stage was statistically higher in GAMPD.The occurrence of micropapillary component in metastatic lymph nodes positively correlated with the proportion of mieropapillary pattern in primary lesions.EMA staining on the stroma-facing surface of tumor micropapillae was demonstrated in 52.1%(38/73)of the cases.As compared with EMA-negative GAMPD, EMA-positive GAMPD was more in the stomach(P=0.018).and with more metastatic lymph nodes(6.6 4-5.8 vs 3.8 ±4.7, P=0.029).The rate of IMP3 expression in EMA-positive GAMPD was 86.8%(33/38),which was higher than that in conventional adenocarcinoma.In contrast.the rate of E-cadherin expression in GAMPD was lower than that in conventional adenocarcinoma.Conclusions GAMPD is a distinctive variant of gastrointestinal adenocarcinomas and different from conventional adenocarcinoma in tumor morphology.immunophenotype and biologic behavior.It carries an aggressive clinical course and poor prognostic outcome.Immunohistochemical study for EMA.IMP3 and E-cadherin would be helpful in the diagnosis and prognostic evaluation of GAMPD.     

Zoledronic acid inhibits lipopolysaccharide-induced osteoclast differentiation by regulating NLRP3 signaling pathway北大核心

BACKGROUND: Zoledronic acid can inhibit bone resorption, but whether it can inhibit inflammatory bone disease and its related mechanisms are completunclear. OBJECTIVE: To investigate the effect of zoledronic acid on the proliferation and differentiation of osteoclasts induced by lipopolysaccharide. METHODS: RAW264.7 cells were treated with lipopolysaccharide for osteoclastic induction and dyed with tartrate-resistant acid phosphatase and F-actin. RAW264.7 cells were cultured in vitro and divided into blank control group (no intervention), control group (treated with lipopolysaccharide), and 0.1, 1, 5 μmol/L zoledronic acid groups (lipopolysaccharide+0.1, 1, 5 μmol/L zoledronic acid). After 6 hours of culture, the level of tumor necrosis factor α in the supernatant was detected by ELISA, and the protein expression levels of NLRP3, caspase-1, interleukin-1β, cleaved-caspase-1 and tumor necrosis factor α were detected by western blot assay. On the 5th day of culture, the formation of osteoclasts was observed by tartrate-resistant acid phosphatase staining, and the expression of actin rings in osteoclasts was observed by F-actin staining. RESULTS AND CONCLUSION: (1) Lipopolysaccharide could induce RAW264.7 cells to differentiate into osteoclasts. (2) The level of tumor necrosis factor α was higher in the control group than the blank control group (P < 0.05) and lower in the 0.1 and 5 μmol/L zoledronic acid groups than the control group (P < 0.05). Results from tartrate-resistant acid phosphatase and F-actin staining indicated that 1 and 5 μmol/L zoledronic acid could inhibit lipopolysaccharide-induced differentiation of RAW264.7 cells into osteoclasts. (3) Compared with the control group, 0.1, 1, and 5 μmol/L zoledronic acid could inhibit the protein expression of NLRP3, caspase-1, interleukin-1β, and tumor necrosis factor α (P < 0.05), while 1 and 5 μmol/L zoledronic acid could inhibit the protein expression of cleaved-caspase-1 (P < 0.05). (4) To conclude, zoledronic acid can inhibit osteoclast formation induced by lipopolysaccharide, which acts possibly through regulating the NLRP3 signaling pathway. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

靶向性反向半胱氨酸天冬氨酸蛋白酶3重组腺病毒诱导肝癌细胞凋亡的实验研究

Objective To investigate the effect and specificity of adenovirus containing r-caspase-3 gene on apoptosis of hepatocellular carcinoma cells. Methods The vector α-fetoprotein enhancer-albumin promotor (pAdTrack-EAFP-PALB) was constructed and the r-caspase-3 gene was subcloned into the vector. The linearized shuttle plasmid was homogenously recombined with AdEasy-1 in BJ5183 cells. The candidate clone was analyzed by restriction endonuclease digestion and sequencing, and then pAdeasy-EAFP-PALB/r-caspase-3 vector was digested with Pac Ⅰ and transfected into AD293 cells for packaging and amplifying.Infection titer and rate of recombinant virus was monitored by green fluorescent protein (GFP) expression.The expression of r-caspase-3 was detected by RT-PCR and Western-blot. The apoptosis of HepG2, 7721, L-02 and MDA- MB- 231 cells was detected by FCM method. Results The sequence of shuttle vector pAdTrack-EAFP-PALB/r-caspase-3 was correct after digestion by restriction endonuclease. Vector pAdeasy-EAFP-PALB/r-caspase-3 was identificated by Pac Ⅰ restriction digestion and PCR. The expression of GFP was observed in the transfected AD293 cells. The expression of r-caspase-3 gene was detected in the infected HepG2 cells by RT-PCR and Western-blot. The cells were infected with recombinant r-caspase-3 after 24 hours, and their apoptotic index were as follows: HepG cells, 48.2%; 7721 cells, 17.7%; L-02 cells, 7.3%;M DA- MB- 231 cells, 0%. Conclusion The recombinant of hepatocellular carcinoma - targeting adenovirus containing r- caspase- 3 gene is constructed successfully and can induce the targeted apoptosis of hepatocellular carcinoma cells, which provides the evidences for future research in hepatocellular carcinoma.     

子宫内膜样腺癌中TBX2、PAX9的表达及其相关性

目的 探讨TBX2、PAX9在正常子宫内膜、子宫内膜增殖症和子宫内膜样腺癌(endometrioid adenocarcinoma,EA)组织中的表达及临床病理学意义.方法 采用组织芯片技术和免疫组化检测30例正常子宫内膜组织、30例单纯性增生内膜、30例复杂伴不典型性增生内膜、82例EA组织中TBX2、PAX9蛋白的表达.结果 TBX2蛋白在子宫内膜样腺癌中的阳性表达率明显高于正常子宫内膜和子宫内膜增殖症(P均＜0.01),TBX2过表达与组织学分级、临床分期、浸润程度均有相关性(P＜0.01,P＜0.05,P＜0.01),与淋巴结转移无相关性(P＞0.05);PAX9蛋白在子宫内膜样腺癌中的阳性表达率明显高于正常子宫内膜、子宫内膜单纯性增生(P均＜0.01),而和复杂伴不典型性增生之间没有统计学意义(P＞0.05),在复杂伴不典型增生中表达明显高于正常子宫内膜和单纯性增生内膜(P均＜0.01),PAX9阳性表达与组织学分级、临床分期、浸润程度均有相关性(P＜0.01,P＜0.01,P＜0.05),但与淋巴结转移无相关性(P＞0.05).TBX2与PAX9蛋白呈正相关(rs=0.427,P＜0.01).结论 TBX2和PAX9均在子宫内膜样腺癌中发生、发展中发挥重要作用,联合检测其表达可为子宫内膜样腺癌的早期诊断、预后判断提供有价值的指标.     

β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及意义

目的 通过分析子宫内膜上皮内瘤变(EIN)诊断、分类与子宫内膜增生WHO(2003)分类的关系,探讨β-catenin、Glut-1和PTEN蛋白在子宫内膜样腺癌发生过程中的表达及其意义.方法 根据EIN诊断及分类标准,对83例子宫内膜增生病例进行再分类.采用免疫组织化学SP法,对10例增殖期子宫内膜、83例子宫内膜增生及24例子宫内膜样腺癌组织中β-catenin、Glut-1及PTEN蛋白的表达进行检测.结果 (1)83例子宫内膜增生病例中共检出24例EIN病例,总检出率为28.9%(24/83).24例EIN病例中,来自复杂型不典型性增生16例(66.7%,16/24),但EIN的检出率与不典型增生的分级无明显关系(P＞0.05).(2)β-catenin蛋白在增殖期子宫内膜中呈正常表达,良性子宫内膜增生的异常表达率为10.2%(6/59),而EIN和子宫内膜样腺癌的异常表达率(50%,12/24;66.7%,16/24)分别明显高于良性子宫内膜增生(P＜0.01),但二者间的异常表达率差异无统计学意义(P＞0.05).(3)Glut-1蛋白在增殖期子宫内膜、良性子宫内膜增生组织中均呈低表达,而在EIN和子宫内膜样腺癌中的高表达率分别为58.3%(14/24)和70.8%(17/24),均显著高于增殖期子宫内膜及良性子宫内膜增生(P＜0.01),但二者高表达率间差异无统计学意义(P＞0.05).(4)PTEN蛋白在EIN病例中的失表达率(37.5%,9/24)与子宫内膜样腺癌(62.5%,15/24)、增殖期子宫内膜(2/10)及良性子宫内膜增生(28.8%,17/59)比较差异均无统计学意义(P＞0.05),但子宫内膜样腺癌的失表达率则明显高于增殖期子宫内膜及良性子宫内膜增生病例,其差异均具有统计学意义(P＜0.05).结论 β-catenin蛋白的异常表达和Glut-1蛋白高表达是子宫内膜样腺癌发生过程中的早期事件,二者在区别良性子宫内膜增生、EIN和子宫内膜样腺癌中可能是有用的免疫标志物.PTEN蛋白失表达是子宫内膜样腺癌发生过程中的极早期事件,但将其作为EIN病变的诊断性标志物并不恰当.     

子宫内膜样腺癌组织中PRRX1蛋白的表达及临床意义

目的探讨配对相关同源框1(paired related homoeobox 1,PRRX1)蛋白在子宫内膜样腺癌组织中的表达及临床意义。方法选取安徽医科大学第一附属医院以及安徽医科大学附属巢湖医院267例子宫内膜组织标本,其中正常子宫内膜86例,子宫内膜上皮内瘤变90例,子宫内膜样腺癌91例,均行免疫组化EliVision法检测,观察不同子宫内膜组织中PRRX1表达及子宫内膜样腺癌临床病理特征与PRRX1的关系。结果PRRX1蛋白表达主要定位于子宫内膜样腺癌组织的细胞核中,91例子宫内膜样腺癌组织中PRRX1阳性率为79.1%,高于正常子宫内膜组织(0)、子宫内膜上皮内瘤变组织(10.0%),差异有统计学意义(P<0.05)。子宫内膜样腺癌患者按FIGO分级分类,FIGO1级的PRRX1阳性率低于FIGO 2、3级,差异有统计学意义(P<0.05);按患者年龄、临床分期、有无淋巴结转移分组,PRRX1阳性率差异均无统计学意义(P>0.05)。结论子宫内膜样腺癌组织中的PRRX1表达量高,且与FIGO分级相关。     

Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis.

Many endometrial adenocarcinomas, particularly those of endometrioid type, express estrogen receptors (ERs), progesterone receptors (PRs), and vimentin. This typical immunophenotype is frequently considered a standard against which others are compared when immunohistochemistry is used for differential diagnosis. We tested large numbers of endometrial cancers, enriched for high-grade tumors, to determine whether this reported immunophenotype was valid and whether expression differences between types of endometrial carcinoma could be exploited for diagnostic purposes. Immunohistochemical stains were performed on the following types of endometrial cancers using established methodology: International Federation of Gynecology and Obstetrics (FIGO) grades 1 and 2 endometrioid-42; FIGO grade 3 endometrioid-40; serous-24; clear cell-11; carcinosarcoma-9. In total, 92% of serous carcinomas expressed p16 strongly compared to weak-to-moderate expression of p16 in 7-67% of other tumors (FIGO grades 1 and 2 carcinoma and carcinosarcoma, respectively). A total of 84% of FIGO grades 1 and 2 carcinomas expressed ER compared to 9-54% of other tumors (clear cell and serous carcinomas respectively); 83% of FIGO grades 1 and 2 expressed PR compared to 11-54% of other carcinomas (carcinosarcoma and serous carcinoma, respectively). Most carcinomas were negative for monoclonal carcinoembryonic antigen (mCEA), and those that were positive showed mostly only focal membrane expression. Vimentin was expressed in nearly every tumor. Most tumors were diffusely vimentin positive, but a large range of expression patterns, from focal to diffuse and from weak to strong, was noted. Only 70% of FIGO grades 1 and 2 endometrioid carcinomas and 26% of grade 3 endometrioid carcinomas possessed the reportedly characteristic endometrial cancer immunophenotype p16 (-), ER (+), PR (+), mCEA (-), and vimentin (+). Endometrial cancers demonstrate substantial immunophenotypic diversity that remained apparent even within groups of similar histologic subtype and grade. ER, PR, and p16 expression was more illustrative of tumor type and degree of differentiation than they were of endometrial origin. In contrast, the vimentin-positive/CEA-negative phenotype remained the most constant among all endometrial cancers.     

EphA2及其配体在子宫内膜样腺癌中的表达及其与血管生成的关系

 目的： 探讨生促红素肝细胞受体A2 （EphA2）及其配体ephrin-A1在子宫内膜样腺癌组织中的表达及其与肿瘤血管生成的关系。方法： 利用免疫组织化学法检测56例子宫内膜样腺癌、20例子宫内膜增生过长、30例正常子宫内膜增殖期和30例分泌期组织中EphA2、ephrin-A1、雌激素受体（ER）和孕激素受体（PR）的表达,并采用CD34抗体标记微血管内皮细胞,计算微血管密度(MVD)。分析EphA2和ephrin-A1的表达与MVD之间的相关性及其与子宫内膜样腺癌临床病理特征的关系。结果： 子宫内膜样腺癌组织中EphA2和ephrin-A1的表达显著高于子宫内膜样增生过长及正常子宫内膜(P<0.05);EphA2和ephrin-A1表达水平及MVD值与子宫内膜样腺癌FIGO分期、肿瘤分化程度、肌层浸润深度、淋巴微血管浸润和孕激素受体表达有关(P<0.05);Spearman等级相关分析表明EphA2和ephrin-A1表达分别与MVD呈显著正相关(r=0.476,P<0.05;r=0.501,P<0.05)。结论： EphA2及其配体ephrin-A1在子宫内膜样腺癌中高表达,可能参与了肿瘤血管生成和孕激素抵抗。     

端粒酶逆转录酶和c-myc基因在子宫内膜样癌及子宫内膜增生中的表达

目的　探讨端粒酶逆转录酶 (hTERT)及c myc基因在子宫内膜增生及癌变过程中的作用、意义及二者相关性。方法　所用标本包括 14例子宫内膜单纯增生 ,8例复合增生 ,10例不典型增生 ,42例内膜样癌 ,用原位杂交法检测hTERT和c mycmRNA表达。结果　 (1)hTERT在子宫内膜单纯、复合、不典型增生病变和内膜样癌中阳性结果分别 2 / 14、4/ 8、8/ 10和 92 9% (3 9/ 42 ) ,前两组均为弱阳性表达 ,后两组多为中度和强阳性 ,统计分析表明不典型增生病变和内膜样癌中hTERT表达高于单纯和复合增生 (P <0 0 5)。c myc在子宫内膜单纯、复合、不典型增生病变和内膜样癌中阳性结果分别 3 / 14、1/ 8、5/ 10和 54 8% (2 3 / 42 ) ,后两组c myc阳性率显著高于前两组 (P <0 0 5) ;不典型增生病变的c myc阳性水平高于单纯及复合增生 (P <0 0 5)。(2 )hTERT阳性水平与内膜样癌分化相关(P <0 15) ;c myc阳性率随内膜样癌浸润深度增加而递增 (P <0 0 5)。 (3 )子宫内膜增生和内膜样癌各组中hTERT与c myc表达均不相关 (P >0 0 5)。结论　hTERT及c myc基因过表达与子宫内膜不典型增生及恶性转化相关 ,并与内膜样癌演进以及不良预后有关 ,但其两者表达之间无相关性     

子宫内膜癌组织中Id-1、VEGF-C和EGFR的表达及临床意义

目的探讨Id-1、VEGF-C和EGFR在正常子宫内膜、子宫内膜增殖症和内膜癌组织中的表达及临床病理学意义。方法采用组织芯片技术和免疫组化检测30例正常子宫内膜组织、30例单纯性增生过长、30例复杂性增生伴不典型增生、72例子宫内膜癌组织中Id-1、VEGF-C和EGFR蛋白表达。结果Id-1、VEGF-C和EGFR蛋白在子宫内膜腺癌组织中的阳性表达率明显高于正常子宫内膜和子宫内膜增殖症(P0.01),Id-1过表达与组织学分级、临床分期、浸润程度和淋巴结转移有关(P0.01,P0.01,P0.05,P0.05);VEGF-C和EGFR阳性表达均与临床分期、浸润程度和淋巴结转移有关(P0.05),与组织学分级无关;Id-1与VEGF-C和EGFR蛋白表达呈正相关(rs=0.625,P0.01;rs=0.313,P0.008)。结论Id-1蛋白参与VEGF-C和EGFR调控,指示其可能与子宫内膜癌的发生发展有关,联合检测可作为判断子宫内膜癌浸润和转移的重要指标。     

Localization of MT1-MMP, TIMP-1, TIMP-2, and TIMP-3 messenger RNA in normal, hyperplastic, and neoplastic endometrium. Enhanced expression by endometrial adenocarcinomas is associated with low differentiation

We studied membrane-type matrix metalloproteinase-1 (MT1-MMP), tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, and TIMP-3 messenger RNA (mRNA) using in situ hybridization to elucidate their temporal and spatial expression patterns in normal, hyperplastic, and neoplastic endometrium. All mRNAs studied were expressed weakly in proliferating endometrium but were induced strongly in late secretory endometrium except MT1-MMP. Endometrial hyperplasia samples did not show increased MT1-MMP or TIMP mRNA expression, indicating that the overall expression patterns in hyperplasia are comparable to those in proliferating endometrium under estrogen effect and that synthesis of extracellular matrix proteins, rather than degradation, predominates in this condition. Exceptionally, stromal cells in areas of desquamation were seen to express focally intense MT1-MMP mRNA in hyperplasia samples. All mRNAs investigated were expressed increasingly in endometrial adenocarcinomas, especially in less differentiated carcinomas. Furthermore, gelatin zymography revealed higher functional degradative activities in carcinoma tissues than in normal endometrium. Our results indicate that MT1-MMP expression, together with that of TIMPs, is involved most notably in normal endometrium under progesterone effect and, without being connected to cyclic hormonal levels, has an important role in the invasive growth of endometrial adenocarcinomas.     

Differential diagnosis of endometrial hyperplasia and carcinoma by computerized image cytometry of cell proliferation, apoptosis and Bcl-2 expression.

BACKGROUND: The differential diagnosis between atypical endometrial hyperplasia and endometrial carcinoma is often difficult and based on controversial criteria. Cell kinetic parameters may be helpful. DESIGN: Cell proliferation, apoptosis and Bcl-2 expression were evaluated in benign endometrium, non atypical and atypical endometrial hyperplasia and endometrial carcinoma. The results were compared by one way analysis of variance and Bonferroni T tests. RESULTS: Cell proliferation was significantly higher (p < 0.01) in endometrial adenocarcinoma (25.6 percent) than in atypical hyperplasia (17.1 percent) and non-atypical hyperplasia (7.5 percent) of the endometrium. Apoptosis was observed in 12.3 percent of endometrial adenocarcinomas and less frequently in atypical hyperplasia (7.4 percent) and non-atypical hyperplasia of the endometrium (5.8 percent). Bcl-2 expression was significantly lower (p < 0.002) in endometrial adenocarcinoma (1.7 percent) than in atypical hyperplasia (4.2 percent) and non-atypical hyperplasia (5.3 percent) of the endometrium. In benign endometrium, cell proliferation and Bcl-2 expression were significantly higher during the proliferative phase while the rate of apoptosis was significantly higher during the secretory phase. CONCLUSIONS: Our data suggests that cell proliferation, apoptosis and Bcl-2 expression could be helpful when distinguishing endometrial carcinoma from non-atypical or atypical endometrial hyperplasia.     

子宫内膜增生及内膜癌中PTEN、Ki-67蛋白的表达

目的　研究子宫内膜增生组织及内膜癌组织中PTEN、Ki 6 7蛋白的异常表达 ,探讨其与子宫内膜癌变的关系及作为早期癌变生物学标志的可能性。方法　应用免疫组化S P法对 12例正常增生期子宫内膜组织、4 0例子宫内膜增殖症组织、4 2例内膜腺癌组织中PTEN、Ki 6 7蛋白的表达进行研究。结果　在正常增生期子宫内膜、子宫内膜增殖症 (单纯增生、复杂型增生、不典型增生 )、子宫内膜腺癌组织中PTEN蛋白的阳性表达率呈递减趋势 ;Ki 6 7蛋白的阳性表达率呈递增趋势。等级相关分析结果显示PTEN、Ki 6 7表达异常与子宫内膜组织学分级均显著相关 (相关系数r分别为 - 0 5 4 1和 0 4 96 ,P值均<0 0 1)。子宫内膜癌与除不典型增生外的子宫内膜增殖症组织及正常增生期子宫内膜组织的PTEN、Ki 6 7蛋白表达差异有显著性 ,正常增生期子宫内膜、单纯增生与不典型增生组织的PTEN蛋白表达差异有显著性 ,不典型增生与单纯增生组织的Ki 6 7蛋白表达差异有显著性。PTEN、Ki 6 7蛋白表达存在负相关性 (r =- 0 4 2 8,P <0 0 1)。PTEN、Ki 6 7蛋白的表达与子宫内膜癌的手术分期、组织学分级、肌层浸润无关 (P >0 0 5 )。结论　PTEN、Ki 6 7蛋白的异常表达与子宫内膜的癌变过程相关 ,PTEN基因表达异常及细胞增殖异常与子宫内膜