乳腺癌组织中HER-2、ER和PR的表达及意义

应用免疫组化MaxVision二步法检测98例乳腺癌和26例癌旁正常的乳腺组织中的雌激素受体(ER)、催乳素(PR)和甾体激素受体和人类表皮生长因子受体(HER-2).结果 HER-2、ER和PR在乳腺癌中阳性表达率分别为20.4%、53.1%、50.0%,癌旁乳腺组织分别为0、42.3%和100.0%,两组织中HER-2和PR阳性表达率相比,P均＜0.05.乳腺癌组织中HER-2、ER和PR的表达分别与组织学分级有关,同时PR的表达还与肿瘤大小、患者年龄有关(P均＜0.05).乳腺癌中HER-2的表达与ER呈负相关(r=-0.234,P＜0.05),ER和PR呈显著正相关(r=0.695,P＜0.01).认为HER-2、ER和PR与乳腺肿瘤的发生和发展密切相关,可用来指导临床用药和判断预后.     

DNA修复基因Hrad51和转移抑制基因nm23在乳腺肿瘤中的表达及生物学意义

目的 探讨DNA 修复基因Hrad51和转移抑制基因nm23 在乳腺肿瘤中的表达及生物学意义.方法 应用S-P免疫组化法,分别检测了Hrad51 蛋白和nm23蛋白在乳腺癌、乳腺纤维腺瘤、乳腺小叶增生、导管上皮不典型增生、腺癌癌旁正常组织中的表达情况.结果 (1) Hrad51蛋白和nm23蛋白在乳腺癌组的表达与乳腺纤维腺瘤、乳腺小叶增生、导管上皮不典型增生、腺癌癌旁正常组织中的表达存在显著差异(均P＜0.01);(2) 乳腺癌中hrda51蛋白的阳性表达与肿瘤组织分级呈正相关(P＜0.01),与nm23、ER、PR的阳性表达呈负相关(均P＜0.01).(3) 乳腺癌中nm23的阳性表达与肿瘤组织分级呈负相关(P＜0.01),与ER的阳性表达呈正相关(P＜0.05),与PR的阳性表达无相关性(P＞0.05).(4) 乳腺癌发生淋巴结转移与nm23、ER的阳性表达呈负相关(均P＜0.01),与Hrad51的阳性表达呈正相关(P＜0.01),与PR的阳性表达无相关性(P＞0.05).结论 (1)Hrad51蛋白在不同病变乳腺组织中呈现不同表达,在乳腺癌组织中存在高度表达;(2)nm23蛋白也在不同病变乳腺组织中呈现不同表达,在乳腺癌组织中存在低表达;(3)检测Hrad51 蛋白和nm23蛋白的表达情况有望成为评价乳腺癌患者预后的一个新指标.     

分化抑制因子Id1在老年女性乳腺浸润性导管癌中的表达及意义

目的 探讨老年乳腺浸润性导管癌中分化抑制因子(Id)1的表达及临床意义.方法 采用免疫组化S-P法检测10例正常乳腺、60例浸润性导管癌组织中Id1的表达,并分析其与乳腺癌临床病理特征的关系.结果 Id1在老年乳腺浸润性导管癌中的表达率(18.07±11.10)%,较正常乳腺组织中表达率[(1.39±1.57)%]显著性增高(P＜0.01);Id1在Ⅰ、Ⅱ级老年乳腺浸润性导管癌中表达阳性率显著低于Ⅲ级[分别为(12.55±5.12)%、(16.46±8.88)%和(37.61±6.84)%,P＜0.01)];Id1在老年乳腺浸润性导管癌中的表达与ER、PR表达呈负相关(r=-0.529,P＜0.01;r=-0.483,P＜0.01),而与CerbB-2表达、患者年龄、肿瘤大小、淋巴结转移无关(P>0.05).结论 Id1的表达增强可能与老年乳腺浸润性导管癌的发生发展有关,Id1的检测有助于老年乳腺浸润性导管癌的诊断和恶性程度的判断.     

老年女性乳腺癌细胞中C-erbB-2、P53、ER和PR的表达及临床意义

目的 探讨C-erbB-2、P53、ER和PR蛋白在老年乳腺癌患者中的表达及其临床意义.方法 采用免疫组化S-P方法,检测113例乳腺癌组织及其癌旁正常乳腺组织中C-erbB-2、P53、ER和PR蛋白的表达情况.结果 在113例乳腺癌中C-erbB-2、P53、ER和PR蛋白阳性表达率分别为77.9% (88/113)、73.5% (83/113)、62.8% (71/113)和57.5% (65/113);C-erbB-2和P53阳性表达率与临床分期、有无淋巴结转移有关(P＜0.05);C-erbB-2、P53、ER和PR阳性表达率与肿瘤大小无关(P＞0.05).结论 联合检测乳腺癌C-erbB-2、P53、ER和PR基因蛋白对判断预后和指导内分泌治疗有实用价值.     

乳腺癌患者术前雌、孕激素受体的表达及意义

术前对68例乳腺癌患者行细针穿刺(FNA)涂片,用免疫细胞化学(ICA)检测(ABC法)雌激素受体(ER)、孕激素受体(PR)在涂片上的表达;同时应用免疫组化检测相应术后组织切片上ER、PR的表达.结果FNA涂片ICA检测ER阳性率为64.7%(44/68),PR的阳性率为39.7%(27/68);在组织切片上ER的阳性率为58.8%(40/68),PR的阳性率为36.7%(25/68).ER、PR在FNA涂片上的表达与组织切片上的表达无显著差别(P＞0.05).ER在FNA涂片上的表达情况与组织学分级、临床分期呈显著负相关(P＜0.05),腋淋巴结阴性者显著高于腋淋巴结阳性者(P＜0.05),与肿瘤大小无关;PR的表达与组织学分级明显负相关(P＜0.05),与其它指标无关.认为FNA与ICA相结合,对于乳腺癌的早期诊断、指导治疗和判断预后具有重要意义.     

PLK1和PCNA在乳腺癌组织中的表达及临床意义

目的 探讨乳腺癌组织中PLK1、增殖细胞核抗原（PCNA）的表达及其临床意义。方法 应用免疫组织化学S-P法检测32例乳腺癌患者癌组织及16例乳腺良性增生患者乳腺增生组织中PLK1、PCNA的表达。结果 乳腺癌组织中PLK1、PCNA的阳性表达率分别为56、3％（18／32）、71．9％（23／32），PLK1表达与年龄、组织学类型、肿瘤大小、淋巴结状态、肿瘤分期及人类表皮生长因子受体-2（HER-2）的表达等因素无关（P均〉0．05），与肿瘤分化程度、雌激素受体（ER）、孕激素受体（PR）表达有关（P均〈0．05）。PCNA的表达与肿瘤分化程度、ER表达有关（P均〈0．05）；与年龄、组织学类型、肿瘤大小、淋巴结状态、PR及HER-2表达等因素无关（P均〉0．05）。乳腺良性增生组织中PLK1、PCNA表达均为阴性或弱表达。结论 PLK1在乳腺癌组织中表达具有一定肿瘤特异性，有望成为乳腺癌治疗的新靶点。     

ER、PR、C-erbB-2、HMFG在乳腺癌组织中的表达及临床意义

目的探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体-2（C-erbB-2）、人乳脂肪球膜蛋白（HMFG）的表达及意义。方法选择手术切除的乳腺癌组织58份（肿瘤组）及癌旁正常乳腺组织58份（对照组）,采用免疫组化EnVision法检测两组ER、PR、C-erbB-2和HMFG表达水平,并分析各指标间及与乳腺癌临床参数的关系。结果乳腺癌组C-erbB-2表达明显高于对照组（P〈0.05）,余指标两组无统计学差异。C-erbB-2阳性表达与乳腺癌组织学分型及腋窝淋巴结转移有关,HMFG阳性表达与导管癌组织学分级相关;相关分析示ER与PR、HMFG表达呈正相关,其他各指标间无相关性。结论 ER、PR、C-erbB-2和HMFG与乳腺癌的发生、发展有关,四项指标联合检测有助于评价乳腺癌的生物学行为,进而指导治疗及预后判断。     

老年乳腺癌组织中S100A11的表达与病理特征分析

目的 探讨S100A11在老年乳腺癌组织中的表达及其与临床特征的关系.方法 选取我院肿瘤科56例经乳腺癌手术治疗后标本,用免疫组化检测S100A11在癌组织与癌旁组织中的表达.分析S100A11与患者绝经与否,淋巴结转移,临床分型,肿块大小,激素等临床特征的关系.结果 S100A11在乳腺癌中阳性率为76.8％,明显高于在周围组织的阳性率38.9％ (P ＜0.05).在56例癌组织里,S100A11蛋白阳性和患者肿块大小、临床分期、ER、PR、HER-2、淋巴结是否转移和绝经关联不具有统计学意义(P＞0.05).而早期浸润型阳性率37.5％,浸润非特殊型阳性率85.4％,差异具有统计学意义(P＜0.05),S100A11蛋白阳性与癌细胞浸润有关.结论 S100A11在老年乳腺癌组织中的阳性率较高,其与患者肿块大小、临床分期、ER、PR、HER-2、淋巴结是否转移和绝经等乳腺癌临床特征的关系不大.     

CD44V3、CD44V6和Ki-67在乳腺癌组织中的表达及意义

目的 探讨乳腺癌组织中CD44V3、CD44V6和Ki-67的表达及其与乳腺癌生物学行为的关系.方法 采用组织芯片技术结合免疫组化法检测60例乳腺浸润性导管癌和20例正常乳腺组织中的CD44V3、CD44V6和Ki-67的表达,并分析其与临床病理参数的关系.结果 乳腺癌组织中CD44V3、CD44V6和Ki-67的阳性表达率分别为41.7%、58.3%和68.3%,明显高于正常乳腺组织(P均＜0.05).乳腺癌组织中CD44V6和Ki-67的表达与乳腺癌组织病理分级、淋巴结转移有关(P＜0.05),同时CD44V6的表达与肿瘤的远处转移与否也有关(P＜0.05).乳腺癌组织中CD44V6与Ki-67的表达成正相关(r=0.587,P＜0.01).结论 CD44V6和Ki-67与乳腺癌的恶性生物学行为密切相关,可作为预测乳腺癌转移潜能的指标.     

PTEN在乳腺癌中的表达及其与转移的关系

目的 通过检测PTEN基因在乳腺癌组织中的表达探讨其临床病理意义.方法 采用逆转录聚合酶链反应(RT-PCR)检测PTEN在40例乳腺癌中的表达.结果 乳腺癌组织与正常乳腺组织和癌旁组织PTEN的表达有显著差异(P＜0.01,P＜0.05).PTEN在早期浸润性癌和晚期浸润性癌阳性表达率差异显著(P＜0.05);在淋巴结转移组与无淋巴结转移组检出阳性率差异显著(P＜0.01).结论 PTEN表达与乳腺癌临床病理特征和生物学行为存在密切关系;PTEN基因是乳腺癌细胞增生活跃的重要影响因素.     

乳腺癌原发灶及淋巴结转移灶中ER、PR表达及临床意义

目的探讨乳腺癌原发灶和淋巴结转移灶中雌激素受体（ER）、孕激素受体（PR）表达及其与肿瘤分期、病理类型的关系。方法采用免疫组化SP法,检测36例乳腺癌术后患者原发灶和淋巴结转移灶中的ER、PR表达。结果乳腺癌原发灶中的ER阳性率69．5％、PR阳性率55．6％,淋巴结转移灶中分别为63．9％、44．4％;原发灶和淋巴结转移灶中的ER、PR表达呈正相关（P均〈0．01）,与肿瘤分期、病理类型无明显相关性（P均〈0．01）。结论判断乳腺癌患者的预后应综合考虑其原发灶和转移灶的生物学特性。     

Expression of aldehyde dehydrogenase 1 in colon cancer

ObjectiveTo study the expression of ALDH1 in colon cancer and its clinical significance.MethodsThe expression of ALDH1 was examined in 98 surgical specimens of primary colonic carcinoma and 15 normal colon tissues with immunohistochemistry method. The correlations of the expression with clinicopathological parameters and prognosis of colon cancer were analyzed.ResultsThe positive rate of expression of ALDH1 was 76.5% (75/98) in the cancer tissues and 13.3% (2/15) in normal colon tissues. There were an obvious statistical difference (P<0.05) between the two groups. The ALDH1 expression was significantly correlated with the histological grade, TNM stages and lymph node metastasis in colon cancer (P<0.05). It was also related with patients' survival time, those with positive expressions had a poor prognosis (P<0.05).ConclusionsThe results suggeste that the overexpression of ALDH1 plays important roles in proliferation and progression in colon cancer, the ALDH1 may be a valuable marker to predict the biological behavior and trend of metastasis of colon cancer.     

BRCA1 regulates human mammary stem/progenitor cell fate

Although it is well established that women with germ-line mutations in the BRCA1 gene have a greatly increased lifetime incidence of breast and ovarian cancer, the molecular mechanisms responsible for this tissue-specific carcinogenesis remain undefined. The majority of these breast cancers are of the basal-like phenotype characterized by lack of expression of ER, PR, and ERBB2. Because this phenotype has been proposed to resemble that of normal breast stem cells, we examined the role of BRCA1 in human mammary stem cell fate. Using both in vitro systems and a humanized NOD/SCID mouse model, we demonstrate that BRCA1 expression is required for the differentiation of ER-negative stem/progenitor cells to ER-positive luminal cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells displaying the stem/progenitor cell marker ALDH1 and a decrease in cells expressing luminal epithelial markers and estrogen receptor. In breast tissues from women with germ-line BRCA1 mutations, but not normal controls, we detect entire lobules that, although histologically normal, are positive for ALDH1 expression but are negative for the expression of ER. Loss of heterozygosity for BRCA1 was documented in these ALDH1-positive lobules but not in adjacent ALDH1-negative lobules. Taken together, these studies demonstrate that BRCA1 plays a critical role in the differentiation of ER-negative stem/progenitor cells to ER-positive luminal cells. Because BRCA1 also plays a role in DNA repair, our work suggests that loss of BRCA1 may result in the accumulation of genetically unstable breast stem cells, providing prime targets for further carcinogenic events.     

Prognostic value of epidermal growth factor expression in breast cancer

A series of 198 female breast cancer biopsies were analysed immunohistochemically for the expression of epidermal growth factor (EGF), with special emphasis on its prognostic significance. A total of 67/198 tumours (33.8%) were EGF-positive, 24 (12%) of which showed strong expression of EGF. EGF was usually expressed in the cytoplasm of the cancer cells but, in 22 cases, the normal ducts adjacent to the cancer showed positive staining as well. Strong EGF expression was related to distant metastases at diagnosis (P=0.04). Oestrogen(ER)- and progesterone-receptor(PR)-negative tumours showed EGF positivity with equal frequency (P=0.05 in both). Axillary lymph node status, histological type, tumour size, histological grade, S-phase fraction, mitotic index or cancer recurrence did not show any statistical correlation with EGF expression. Tumour size (P=0.007), axillary lymph node involvement (P=0.003) and ER content (P=0.03) were independent prognostic factors in multivariate survival analysis, whereas EGF positivity, as an independent factor, had no effect on survival. In univariate analysis, however, EGF positivity predicted a more favourable outcome in axillary-lymph-node-positive tumours (P=0.04). The results suggest that immunohistochemical assessment of EGF expression has hardly any clinical significance in addition to the well-established prognostic factors in breast cancer.Abbreviations EGF epidermal growth factor - EGFR EGF receptor     

诱导型一氧化氮合酶、环氧合酶-2与乳腺癌淋巴管生成的关系及其临床意义

目的探讨诱导型一氧化氮合酶(iNOS)和环氧合酶-2(COX-2)在乳腺癌间质淋巴管生成中的作用机制及其临床意义。方法收集乳腺浸润性导管癌组织90例和乳腺纤维腺瘤组织30例,应用寡核苷酸探针原位杂交法检测组织中iNOS和COX-2的mRNA表达,另以Elivision免疫组化法检测淋巴管内皮细胞透明质酸受体1(LYVE-1)和血管内皮生长因子-C(VEGF-C)蛋白的表达情况,分析iNOS和COX-2与LYVE-1标记的淋巴管密度(LVD)以及VEGF-C的关系。结果在90例乳腺癌中iNOS、COX-2的mRNA阳性率分别为66.7%、68.9%,LVD为(8.03±2.26)个/HPF,VEGF-C表达阳性率为47.8%,与良性对照组比较均有显著差异(P<0.01)。iNOS mRNA表达与乳腺癌肿瘤大小、分期、LVD和VEGF-C表达呈正相关(P<0.01);COX-2 mRNA表达与肿瘤分级、淋巴结转移、分期和LVD呈正相关(P<0.05),与VEGF-C表达无显著相关(P>0.05);iNOS和COX-2的mRNA阳性表达呈正相关(P<0.05)。结论 iNOS和COX-2具有协同促进乳腺癌淋巴管生成及侵袭转移的作用,有望在乳腺癌的临床预后判断及靶向治疗中发挥作用。     

Relationship between Egr—1 gene expression and apoptosis in esophageal carcinoma and precancerous lesions

AIM: To study the expression of early growth response gene-1 (Egr-1 gene) and Bcl-X/(L) protein and its relationship with the cell apoptosis in human esophageal carcinoma (EC) and precancerous lesions. METHODS: In situ hybridization(ISH), immunohistochemistry (IHC) and TUNEL method were used respectively to detect Egr-1mRNA, Egr-1 protein, apoptosis related-protein Bcl-X/(L) and cell apoptosis in situ from 66 cases of esophageal squamous cell carcinoma and their upper cut edge and paracancerous mucosa. RESULTS: Egr-1 gene in situ hybridization, Bcl-X/(L) immunohistochemistry positive products were located in the cytoplasm, while Egr-1 immunohistochemistry and TUNEL positive signal were located in the nuclei. The apoptosis index(AI) and the frequency of apoptosis occurrence were increased gradually from precancerous lesion to cancer (P<0.01) and the expression of Egr-1mRNA and Egr-1 protein in dysplasia was the highest among all specimens (P<0.01). The AI of Egr-1 positive cancer tissues was much higher than that of Egr-1 negative cancer tissues (P<0.01), while the AI of Bcl-X/(L) positive cancer tissues was much lower than that of Bcl-X/(L) negative cancer tissues (P<0.01). The AI and Egr-1 expression were not correlated with invasiveness and lymphatic metastasis in EC. CONCLUSION: Cell apoptosis was present through esophageal carcinogenesis. The expression of Egr-1 mRNA and Egr-1 protein were high in precancerous lesion of esophagus. The AI was increased significantly in Egr-1 positive squamous cell carcinoma. Egr-1 might promote apoptotic effect. Egr-1 expression and cell apoptosis may have an important biological significance in esophageal carcinogenesis.     

肿瘤抑制基因PTEN蛋白在乳腺癌中的表达及意义

采用免疫组化法检测 138例乳腺癌患者的 PTEN蛋白、ER和 PR的阳性表达。结果示 PTEN阳性率(4 7.83% )与 ER阳性率 (39.86 % )和 PR阳性率 (4 2 .0 3% )接近。PTEN阳性病例中淋巴结转移率 (2 7.6 9% )远低于 PTEN阴性者 (6 1.6 4% ) ,两者差异显著 (P〈0 .0 5 )。认为 PTEN、ER和 PR表达具有较强的一致性 ,推测 PTEN基因的突变和缺失可能与乳腺癌的发生、发展有关 ;PTEN与 ER的表达与淋巴结转移有明显相关性 ,可作为判断乳腺癌预后的指标。     

Studies on estrogen receptor in normal and cancerous human uterine endometrium by immunological methods

The presence of cytosol estrogen receptor (ER) and the ER of nuclear extracts in normal uterine endometrium and endometrial adenocarcinoma tissues were determined by radioreceptor assay (RRA) and enzyme immunoassay (EIA). In addition the intracellular localization of ER and tissue distribution of ER positive cells was demonstrated by immunocytochemical assay (ICA). The levels of cytosol ER measured by EIA and RRA had a significant correlation in normal endometrium (r = 0.90) (P less than 0.01) and endometrial adenocarcinoma (r = 0.96) (P less than 0.01) as well as in breast cancer (r = 0.93) (P less than 0.01). The ER measured by immunocytochemical method using the monoclonal anti-ER antibody obtained from breast cancer cells was applicable to the detection of the ER in uterine endometrial tissues. In endometrial adenocarcinoma, the levels of cytosol ER in G1 (Highly differentiated adenomatous carcinoma) tissues (187.6 +/- 189.0 fmoles/mg protein) were significantly higher than those in G2 (Moderately differentiated adenomatous carcinoma with partly solid areas) tissues (15.0 +/- 31.9 fmoles/mg protein) (P less than 0.05). The levels of cytosol ER peaked in the late follicular phase (432.0 fmoles/mg protein) and remained low in the other phases. Epithelial cells in the normal endometrium were stained uniformly by ICA, in contrast, ICA stained and non-stained cells existed concurrently in the same endometrial adenocarcinoma tissues. A similar finding was also shown in breast cancer tissues and may be related to the efficacy of anti-estrogenic drugs on the growth of whole cancer tissues.