精原细胞瘤中VEGF、ER及AR的表达及临床意义

目的 探讨精原细胞癌发生、发展中血管内皮生长因子〔VEGF)、雌激素受体(ER)及雄激素受体(AR)的作用。方法 采用免疫组化技术检测精原细胞瘤和前列腺癌中VEGF、ER及AR的表达。结果16例精原细胞瘤中VEGF表达阳性14例,占87.5％,显著高于前列腺癌(P<0.05);AR表达阳性9例,占56.2％,低于前列腺癌(P>0.05);ER表达全部阴性。10例前列腺癌中,VEGF表达阳性4例,占40％;AR表达阳性9例,占90％;ER表达全部阴性。结论 精原细胞瘤中VEGF表达显著升高,对于精原细胞瘤的发生、血管形成和转移有重要意义,阻断VEGF的作用对精原细胞瘤可以达到一定治疗作用。另外精原细胞癌发生和发展可能与雌激素无关,而与雄激素部分有关。     

前列腺癌组织中性激素受体表达的分析

目的:定性分析雄激素受体(AR)、雌激素受体(ER)、孕激素受体(PR)在良性前列腺增生(BPH)和前列腺癌(PCa)组织中的阳性表达,为激素治疗PCa和预后判断提供一定的依据。方法:采用免疫组化DAKO Envision二步法,分析30例BPH与32例PCa标本中AR、ER、PR的阳性表达情况。结果:AR、ER、PR阳性数BPH组分别为22、10、6例;PCa组分别为18、14、2例,两组差异无显著性。随访30例PCa患者术后的生存期表明:AR表达阳性者平均生存时间为6.41年,AR阴性者为4.28年,两者差异有统计学意义(P<0.05)。结论:BPH和PCa患者在性激素受体表达上的差异无显著意义;PCa患者中AR表达阳性者平均生存时间长于AR阴性者,后者的预后较差,对AR阴性者行激素治疗效果不确定。     

p53和VEGF在前列腺癌组织中的表达及临床意义

目的研究p53和血管内皮生长因子（vascular endothelial growthfactor,VEGF）在同一前列腺癌（prostate cancer,Pca）组织中的表达及与Pca临床参数的关系,探讨肿瘤血管形成及调节机制。方法应用免疫组织化学LDP法检测46例Pca组织及20例良性前列腺增生症（benign prostatic hyperplasia,BPH）组织中p53蛋白及VEGF的表达。结果Pca组织中p53与VEGF阳性表达率分别为41.30%（19/46）和71.74%（33/46）,均明显高于BPH组（P〈0.05）;p53与VEGF表达呈明显正相关（P〈0.05）;二者在Pca组织中的表达水平与其病理分级和临床分期均呈正相关（P〈0.05）;p53和VEGF阳性表达的肿瘤复发迅速、易转移,p53阴性而VEGF阳性表达较阴性表达者预后差。结论p53和VEGF与Pca组织学分级？恶性程度和预后密切相关,是检测Pca的较好分子标志物;Pca是典型的血管依赖性病变,p53可能通过p53-VEGF调节旁路途径促进Pca的肿瘤血管形成,联合检测p53和VEGF的表达可作为判断Pca生物学行为及预后的重要指标。     

人肝细胞性肝癌性激素受体的表达

目的：研究人肝细胞性肝癌组织、癌旁组织和正常肝组织中雄激素受体（AR）和雌激素受体（ER）的表达水平及分布规律。方法：应用单克隆抗体免疫组化法检测50例肝细胞性肝癌标本的肿瘤组织、癌旁组织和10例肝内胆管结石的肝组织中AR和ER的表达情况。结果：在肝癌组织、癌旁组织和肝内胆管结石的肝组织中，AR的阳性表达率分别为30％、8％和0％，除癌组织显著高于癌旁组织外（P＜0．01），其它各组无显著性差异（P＞0．05）；ER的阳性表达率分别为12％、10％和20％，在三组中均无显著性差异（P＞0．05），在所有阳性片中，AR和ER的标记指数（LI）均＜25。结论：AR和ER在肝细胞性肝癌组织中的表达率很低。     

Prostatic cancer/benign prostatic hypertrophy. Subcellular distribution of estradiol/androgen receptors

Six microsomal population of estradiol and androgen receptors have been characterized in human benign prostatic hypertrophy (BPH) and prostate cancer (PCa). Estradiol receptor (ER) and androgen receptors (AR) were extracted using 0.6 M KCL and determined by the dextran-coated charcoal method. ER and AR levels were smaller in BPH plasma membranes (PM) than in Pca cases. For functions 3, 4, 6, the ER values in PCa were 25-38% less with regard to BPH ER values. Whereas in PCa, AR values obtained in all fractions were higher when compared to BPH AR values. In benign prostatic hypertrophy and prostatic cancer, ER and AR levels were significantly higher in the nuclear fraction. In the nuclear fraction, ER and AR levels in BPH and PCa were significantly different. The subcellular distribution of AR and ER in BPH and PCa constitutes a reservation mechanism and processing a receptors for their continued growth.     

Androgen Receptor Expression Along with Loss of bcl-2, ER, and PR Expression in Benign and Malignant Apocrine Lesions of the Breast: Implications for Therapy

Abstract: Apocrine lesions of the breast are not uncommon. Limited studies have suggested that apocrine cells may be under the influence of an androgenic, rather than an estrogenic, regulatory system. Furthermore, a recent study has shown that metaplastic apocrine cells of the breast lack expression of bcl-2, a B-cell leukemia/lymphoma gene protein whose expression in the breast is believed to be regulated by estrogen. This study was undertaken to immunohistochemi-cally assess the status of expression of estrogen receptor (ER), progesterone receptor (PR), bcl-2, and androgen receptor (AR), in a series of mammary apocrine lesions ranging from simple metaplasia to metastatic carcinoma, and to determine whether there is any possible interrelationship or correlation between the expression of these hormone receptors and that of bcl-2. Among 102 apocrine lesions (68 benign and 34 malignant) evaluated, 100 (98%) were ER and PR negative; only two intraductal carcinomas (IDCA, 2%) were weakly positive for ER and PR. Bcl-2 was detectable only in these two IDCA, but not in any of the other apocrine lesions. In contrast, AR positivity was evident in 15 of 16 (94%) benign apocrine lesions and 18 of 25 (72%) cancerous apocrine lesions (13 of 16 IDCA, 5 of 8 invasive carcinomas, and 0 of 1 metastatic carcinoma) evaluated; all 7 AR negative cancerous lesions (3 IDCA, 3 invasive carcinomas, and 1 metastatic carcinoma) were poorly differentiated with pronounced atypia. These results suggest that apocrine differentiation appears to be associated with retention of AR positivity and a reversal of the usual mammary hormone receptor expression profile for ER, PR, and bcl-2 oncoprotein. These findings warrant exploration of the value of androgenic hormone manipulations in management of AR-positive apocrine carcinomas.?     

性激素受体在胆囊癌中的表达研究

目的 探讨性激素受体在胆囊癌中的表达。方法 采用免疫组织化学Avidin Biotin Peroxidase Compldex(ABC)方法对106例胆囊癌和61例胆囊良性病变石蜡切片标本进行雌激素、孕激素及雄激素受体检测。结果 胆囊癌中三种受体阳性率分别为67%、57%、44%。性激素受体阳性率与胆囊癌分化程度有密切关系。结论 性激素与胆囊癌发展关系密切。内分泌治疗可能成为治疗胆囊癌的一种方法。     

性激素受体在肝细胞癌的表达及其临床意义

运用Ｓ－Ｐ免疫组化法对３０例手术治疗的男性肝细胞癌患者癌组织,癌周组织及２０例良性病变肝组织的雄激素受体,雌激素受体以及孕激素受体进行了检测。结果;肝癌组织ＡＲ阳性率８０．０％,显著高于癌周组织及良性病变肝组织,Ｐ〈０．０１,后两者比较无显著性差异;癌组织ＥＲ阳性率为４３．３％,显著低于癌周组织,Ｐ〈０．０１,与良性病变肝组织比较无差异;ＰＲ阳性率在３种组织中比较无显著性差异。     

转甲状腺素蛋白在前列腺癌组织中的表达以及与分级分期的关系

目的 探讨转甲状腺素蛋白(TTR)在正常前列腺(NP),良性前列腺增生(BPH)以及前列腺癌组织(Pca)中的表达,以及其表达与Pca分期分级的关系.方法 收集我院10例NP、10例BPH以及52例Pca石蜡标本切片,经常规处理后,行TTR免疫组织化学研究.结果 TTR在81%(42/52例)Pca表达强阳性,而NP和BPH无表达强阳性(P<0.05);Gleason评分8～10分Pca94%(16/17例)TTR表达强阳性,Gleason评分2～4分Pca只有50%(5/10例)TTR表达强阳性(P<0.05);TTR在全部8例D期Pca表达强阳性,A期和B期只有33%(2/6例)和79%(19/24)表达强阳性(P<0.05).结论 TTR可能与Pca的发生有关,其在Pca中的表达与Pca分级及分期有关,有可能作为Pca预后的风险因子.     

Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases

Mullerian adenosarcomas (MAs) are rare mixed mesenchymal and epithelial neoplasms that occur most commonly in the uterus. Although the epithelial component is typically benign, the mesenchymal component of most adenosarcomas morphologically resembles that observed in endometrial stromal tumors and is responsible for their clinical behavior. Thus, the differential diagnosis usually includes not only low-grade endometrial stromal tumors, but also adenofibroma, carcinosarcoma, and embryonal rhabdomyosarcoma especially in small samples. The objective of this study was to ascertain the immunophenotypic profile of the epithelial and mesenchymal components of MAs and delineate possible differences between conventional mesenchymal areas and areas of sarcomatous overgrowth. Representative sections from 35 MAs, 28 of them without sarcomatous overgrowth (MA-NSO) and 7 with sarcomatous overgrowth (MA-SO), were included in the study. Thirty tumors arose in the uterus, 4 were pelvic, and 1 originated in the colon. Adequate blocks were selected and immunostained for estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), CD10, WT1, smooth muscle actin, desmin, AE1/3 cytokeratin, CD34, calretinin, inhibin, c-kit, and Ki-67. The mesenchymal component expressed ER in 21/27 MA-NSOs but in only 1/7 MA-SOs (65% overall). PR was expressed in 21/26 MA-NSOs and 4/7 MA-SOs (76% overall), whereas AR was positive in 10/27 MA-NSOs and 5/7 MA-SOs (35% overall). CD10 was expressed in 23/28 MA-NSOs but in only 2/7 MA-SOs (71% overall), and WT1 positivity was seen in 22/27 MA-NSOs and 6/7 MA-SOs (79% overall). Sixty-seven percent of MAs expressed smooth muscle actin, 32% desmin, including both examples of MA-SOs with rhabdomyoblastic differentiation, and 25% expressed AE1/3 cytokeratin. CD34 expression was found in 35% of the tumors, but it was almost always patchy in distribution and weak in intensity, as was calretinin expression, seen only in 12% of the cases. Expression of c-kit and inhibin in greater than 5% of the tumor cells was not encountered. The median and mean Ki-67 labeling indices were 10% and 12%, respectively (range, <5% to 40%). The median and mean Ki-67 indices were both 5% in MA-NSOs compared with 30% and 28%, respectively, in MA-SOs. The epithelial compartment demonstrated expression for ER (24/32), PR (23/31), and AE1/3 cytokeratin (33/33); rare cases expressed CD10 (4 cases) and AR (1 case). In summary, the immunophenotype of most MAs resembled that of endometrial stromal tumors (positive for ER, PR, WT1, and CD10, with variable expression of muscle markers, AR and cytokeratin). The proliferative rate in the stromal component was strongly related to the presence of sarcomatous overgrowth. ER, PR, and CD10 expression was lost in MA-SOs relative to conventional low-grade stromal areas of mullerian/mesodermal adenosarcomas, reflecting the "dedifferentiation" of this component.     

Simultaneous and sequential determinations of steroid hormone receptors in human breast cancer. Influence of intervening therapy.

Estrogen (ER), progesterone (PgR), and androgen (AR) receptors were measured in two simultaneous or subsequent specimens taken each from 259 patients with breast cancer. We studied in 182 patients results from receptor assays, either from one tumor or from the primary tumor, and a lymph node metastasis, and in 77 sequential biopsies with or without intervening therapy. All assays were performed in a single laboratory, considering 10 fmol/mg cytosol protein bound ligand as receptor positive. The concordance rate in simultaneous ER assays was 85%; however, we found a considerable high discordance rate for PgR in primary tumor and lymph node metastasis (25%). The overall discordance rate in sequential biopsies for ER was 38% and for PgR 25%. This discordance rate was primarily dependent on the receptor quality of the first assay (ER+: 50%, ER-: 24%, PgR+: 68%, PgR-: 9%). Considering only the ER+ and PgR+ cases, we found the greatest discordance rate in the patients having endocrine treatment following the first biopsy (55% and 84%, respectively). We conclude that the receptor status of one tumor biopsy is highly representative for other tumor or lymph node biopsies. Because of the high discordance rate of primarily receptor + cases in subsequent recurrences, the receptor quality of these lesions should be analyzed whenever possible.     

生长抑素受体和雌激素受体在原发性乳腺癌中的表达及其意义

目的研究生长抑素受体(SSTR)与雌激素受体(ER)、孕激素受体(PR)在原发性乳腺癌中的表达及其意义。方法 采用免疫组织化学链霉菌抗生物素蛋白-过氧化酶(SP)法检测SSTR和ER、PR在68例乳腺癌中的表达。结果 在68例乳腺癌中,SSTR阳性表达44例(64.70％),ER、PR阳性表达51例(75.70％),ER、PR和SSTR同时阳性表达阳性41例(60.29％)。ER、PR和SSTR两者表达呈正相关(r=0.651 6,P<0.05)。SSTR阳性患者复发率和死亡率低于SSTR阴性者(P<0.05);SSTR阳性且ER、PR阳性患者复发率和死亡率明显低于SSTR阴性ER、PR阴性患者(P<0.01)。病理分化低的有47例,SSTR阳性表达36例(P>0.05)。结论SSTR表达与ER、PR表达有明显相关性,有可能作为判断乳腺癌预后的指标。     

蛋白激酶Cε在前列腺癌组织中表达的临床意义

目的 探讨蛋白激酶C ε(PKCε)在不同病理类型前列腺组织中的表达及与前列腺癌病理分级、分期的关系。 方法 正常前列腺(NP)组织标本10例、前列腺增生(BPH)组织标本10例、癌旁(PC)组织标本10例、前列腺癌(PCa)组织标本43例。免疫组化法检测各组织中PKCε的表达情况,分析PKCε表达与不同病理类型及PCa分级、分期的关系。 结果 PCa组PKCε表达阳性27例,BPH组无阳性表达,NP组1例,PC组2例,差异有统计学意义(P＜0.05)。PCa组Gleason评分≥8分组中PKCε表达阳性12/13例,2～4分组4/10例,5～7分组11/20例,组间差异有统计学意义(P＜0.05)。T3期PKCε表达阳性10/12例,T4期9/10例,T1、T2期分别为1/6例和7/15例,高分期与低分期组PKCε表达差异有统计学意义(P＜0.05)。PCa转移组PKCε表达阳性9/10例,未转移组18/33例,组间差异有统计学意义(P＜0.05)。PCa患者血清PSA≤20 ng/ml者PKCε表达阳性7/15例,＞20 ng/ml组20/18例,组间差异无统计学意义(P＞0.05)。 结论 PCa组织中PKCε的表达率较高,并且与PCa病理分级、分期呈正相关,临床上可考虑作为PCa预后因子之一。     

Angiogenesis and lymphangiogenesis in stage 1 germ cell tumours of the testis

OBJECTIVE: To determine whether angiogenesis can be used as an additional prognostic indicator in patients with stage 1 germ cell tumours of the testis. PATIENTS AND METHODS: Paraffin sections were assessed immunohistochemically from 51 patients with clinical stage 1 germ cell tumours of the testis (28 seminoma, 23 teratoma) treated by orchidectomy and surveillance only. Sections were analysed for microvascular density (MVD), and expression of the angiogenic factors vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP). In addition, in the seminoma cases the presence of mRNA for the lymphangiogenic factor VEGF-C was examined by in situ hybridization, and its corresponding receptor VEGFR-3 by immunohistochemistry. RESULTS: Teratoma specimens had a significantly higher mean (range) MVD (85, 26-163; P < 0.01) than both seminoma (37, 16-91) and four normal specimens (26, 18-30). Teratoma specimens also had significantly higher VEGF expression than both seminoma and normal specimens (P < 0.01). Despite these differences between groups, and indeed individual tumours, there was no significant correlation between MVD and VEGF, or between either MVD or VEGF and relapse-free survival. TP expression was significantly greater in tumours than in normal specimens (P < 0.02) but with very little inter-tumour variation. VEGF-C mRNA and VEGFR-3 protein were detected in a third to a half of cases, with expression mostly around endothelial vessels. CONCLUSIONS: The marked differences between normal testis and tumours implicate angiogenesis in the biology of germ cell tumours of the testis. In addition, the detection of factors involved in lymphangiogenesis in some seminomas, tumours which initially metastasize primarily to lymph nodes, indicate that although not prognostic in this study, further studies are warranted in both these areas in the search for further prognostic indicators and therapeutic targets.     

5-氟尿嘧啶加奥曲肽对乳腺癌细胞凋亡的影响

目的 探讨５－氟尿嘧啶（５－ＦＵ）加奥曲肽（善得定）对乳腺癌细胞凋亡的影响。方法取手术切除的１６例乳腺癌标本,制备癌单细胞悬液。每例癌细胞均分成４组：５－ＦＵ组（加入５－ＦＵ１０μｇ／ｍｌ）、善得定组（加入善得定０．１μｇ／ｍｌ）、５－ＦＵ加善得定组（加入５－ＦＵ１０μｇ／ｍｌ、善和定０１μｇ／ｍｌ）及对照组（不加任何药物）。用ＤＮＡ断端标记法（ＴＤＴ法）检测乳腺癌细胞癌细胞凋亡率。结果 １６例标     

骨肉瘤肺转移与血管内皮生长因子和微血管密度的关系

目的 探讨骨肉瘤盱市转移与血管内皮生长因子(VEGF)和微血管密度(MVD)的关系.方法 用免疫组织化学法检测30例骨肉瘤组织中VEGF的表达和MVD.结果 VEGF在骨肉瘤中的阳性率表达分别为70.00%(21/30),其中有肺转移的病例阳性率为92.31%(12/13).无肺转移病例的阳性率为52.94%(9/17),差异有统计学意义(P<0:05).骨肉瘤组织中VEGF阳性表达与骨肉瘤的组织学分型无明显相关(P>0.05).骨肉瘤中VEGF表达强度与MVD呈正相关(r=0.799,P<0.01);有肺转移的骨肉瘤患者其瘤组织中MVD与无肺转移的骨肉瘤患者其瘤组织中MVD差异有统计学意义(P<0.05),有肺转移的明显高于无肺转移的病例.结论 VEGF是促进微血管生成的主要细胞因子,检测VEGF表达与MVD值可作为判断肿瘤预后的重要指标.     

转录因子激活蛋白-4在结直肠癌中的表达及与细胞凋亡的相关性

目的 观察转录因子激活蛋白(AP)-4在正常直肠、腺瘤和结直肠癌组织中的表达,探讨其表达与临床病理、转移相关基因血管内皮生长因子(VEGF)和基质金属蛋白酶(MMP)-9的表达、细胞凋亡间的关系.方法 利用组织芯片和免疫组织化学技术,检测正常直肠、腺瘤组织标本各16例及结直肠癌80例中AP-4蛋白的表达,采用逆转录-聚合酶链反应(RT-PCR)方法检测各组VEGF、MMP-9 mRNA的转录水平,以缺口末端标记技术(TUNEL)检测结直肠癌细胞的凋亡指数.结果 (1)正常直肠组织、直肠良性腺瘤、结直肠癌组织AP-4的阳性表达率分别为12.50%(2/16),25.00%(4/16),56.25%(45/80),其中良性直肠组织18.75%(6/32),良性直肠组织AP-4的阳性表达率与结直肠癌组织比较,两者差异有显著的统计学意义(x2=12.96,P<0.01);结直肠癌患者不同年龄、性别、肿瘤部位、大小、血清CEA水平、组织学类型的AP-4表达程度比较,差异无统计学意义(P>0.05);不同分化程度、病理分期、淋巴转移、5年生存率的AP-4表达程度比较,差异有统计学意义(P<0.05);(2)结直肠癌组织VEGF和MMP-9转录水平显著高于正常直肠组织和腺瘤(P<0.05),结直肠癌组织AP-4结合活性增强与VEGF和MMP-9高表达显著相关(P<0.01);(3)结直肠癌AP-4基因表达程度不同的结直肠癌细胞凋亡指数(AI)间的差异有统计学意义(F=58.76,P<0.01).结论 AP-4基因表达升高可能与结直肠癌的发生密切相关,AP-4可能参与了结直肠癌的发生、发展和侵袭转移.     

骨肉瘤肺转移与血管内皮生长因子和微血管密度的关系

目的 探讨骨肉瘤盱市转移与血管内皮生长因子(VEGF)和微血管密度(MVD)的关系.方法 用免疫组织化学法检测30例骨肉瘤组织中VEGF的表达和MVD.结果 VEGF在骨肉瘤中的阳性率表达分别为70.00%(21/30),其中有肺转移的病例阳性率为92.31%(12/13).无肺转移病例的阳性率为52.94%(9/17),差异有统计学意义(P<0:05).骨肉瘤组织中VEGF阳性表达与骨肉瘤的组织学分型无明显相关(P>0.05).骨肉瘤中VEGF表达强度与MVD呈正相关(r=0.799,P<0.01);有肺转移的骨肉瘤患者其瘤组织中MVD与无肺转移的骨肉瘤患者其瘤组织中MVD差异有统计学意义(P<0.05),有肺转移的明显高于无肺转移的病例.结论 VEGF是促进微血管生成的主要细胞因子,检测VEGF表达与MVD值可作为判断肿瘤预后的重要指标.     

骨肉瘤肺转移与血管内皮生长因子和微血管密度的关系

目的 探讨骨肉瘤盱市转移与血管内皮生长因子(VEGF)和微血管密度(MVD)的关系.方法 用免疫组织化学法检测30例骨肉瘤组织中VEGF的表达和MVD.结果 VEGF在骨肉瘤中的阳性率表达分别为70.00%(21/30),其中有肺转移的病例阳性率为92.31%(12/13).无肺转移病例的阳性率为52.94%(9/17),差异有统计学意义(P<0:05).骨肉瘤组织中VEGF阳性表达与骨肉瘤的组织学分型无明显相关(P>0.05).骨肉瘤中VEGF表达强度与MVD呈正相关(r=0.799,P<0.01);有肺转移的骨肉瘤患者其瘤组织中MVD与无肺转移的骨肉瘤患者其瘤组织中MVD差异有统计学意义(P<0.05),有肺转移的明显高于无肺转移的病例.结论 VEGF是促进微血管生成的主要细胞因子,检测VEGF表达与MVD值可作为判断肿瘤预后的重要指标.