乳腺癌p53,c—erbB—2基因蛋白,表皮生长因子受体与雌,孕激素受体…

应用免疫组化ＡＢＣ法检测１００例乳腺癌和１００例乳腺良性病变组织中ｐ５３，ｃ－ｅｒｂＢ－２，ＥＧＦＲ 与ＥＲ，ＰｇＲ的表达，结果显示，乳腺癌各种标记阳性率均高于乳腺良性病变；ＥＲ性率在５０岁以上组高于５０岁以下组（Ｐ〈０．０５），不同病理学类型中各种标记的阳性率亦存在一定差异，乳腺癌中ｐ５３，ｃ－ｅｒｂＢ－２，ＥＧＦＲ和ＥＲ及ＰＲ的表达呈显著负相关（Ｐ〈０．０１），可能成为判断乳腺癌治疗和预后的重     

EGFR与C－erbB－2癌基因蛋白在甲状腺乳头状腺癌中的表达

本文作者研究了上皮生长因子受体（ＥＧＦＲ）和Ｃ－ｅｒｂＢ－２癌基因蛋白在５０例甲状腺癌和６６例甲状腺良性疾患中的表达。５０例甲状腺癌中，ＥＧＦＲ阳性者２６例（５２％），Ｃ－ｅｒｂＢ－２阳性者２５例（５０％）。ＥＧＦＲ和ｃ－ｅｒｂＢ－２共同表达阳性者的淋巴结转移率（９２．８５％）明显高于两者共同表达阴性者（６１．５３％）（Ｐ＜０．０５）。ＥＧＦＲ阳性者ＡｇＮＯＲ数（２．５９±０．６４／核）也明显高于ＥＧＦＲ阴性者（１．３９±０．１８／核）（Ｐ＜０．００１）。ＥＧＦＲ与Ｃ－ｅｒｂＢ－２共同表达阳性，同时ＡｇＮＯＲ计数高的甲状腺癌具有较高的恶性度。因此，对这种病人要予以特别的治疗措施并抓紧随访工作。     

c－erbB－2和EGFR在胃癌中表达的研究

应用ＡＢＣ和ＬＳＡＢ法对７５例胃癌及癌旁组织进行了ｃ－ｅｒｂＢ－２和ＥＧＦＲ表达的研究。结果：１）７５例胃癌ｃ－ｅｒｂＢ－２表达阳性率为１８．７％，阳性表达只限于癌灶，而癌旁组织均为阴性。ｃｅｒｂＢ－２在高分化胃癌、大体局限型胃癌中的阳性率较高（Ｐ＜０．０５）。２）ＥＧＦＲ表达阳性率为６１．３％，癌旁组织、新生血管有阳性表达。ＥＧＦＲ表达与胃癌的大体类型、生长方式、分化程度、淋巴结受累和远处转移至正相关（Ｐ＜０．０５）。３）ｃ－ｅｒｂＢ－２表达与ＥＧＦＲ表达无明显关系。结果说明：ｃ－ｅｒｂＢ－２表达出现于胃粘膜癌变的后期，是恶性细胞的标志；ＥＧＦＲ表达与胃癌的恶性程度有明显关系；ｃ－ｅｒｂＢ－２和ＥＧＦＲ在胃癌中的表达是互相独立的。     

胃癌多基因表达的同步检测

应用ＬＳＡＢ和ＡＢＣ法对７５例胃癌及癌旁组织进行了ｐ５３、ｃ－ｅｒｂＢ－２、ＥＧＦＲ和ｒａｓ表达的研究。结果显示：（１）７５例胃癌ｐ５３、ｃ－ｅｒｂＢ－２、ＥＧＦＲ和ｒａｓ表达阳性率分别为４１．３％、１８．７％、６１．３％和４６．７％。ｐ５３在肠型胃癌中阳性率为５２．６％，高于弥漫型胃癌的２９．７％（Ｐ＜０．０５）；在早期胃癌中阳性率较高（６０．０％），癌旁重度异型增生亦有阳性表达（２／４）。ｃ－ｅｒｂＢ－２阳性表达只限于癌灶，而癌旁组织均为阴性。ｃ－ｅｒｂＢ－２在高分化胃癌中阳性率较高（Ｐ＜０．０５）。ＥＧＦＲ表达与胃癌的大体类型、生长方式、分化程度、淋巴结受累和远处转移呈正相关（Ｐ＜０．０５）。（２）ｃ－ｅｒｂＢ－２和ＥＧＦＲ在胃癌中的表达互相独立。（３）ｒａｓ表达与ＥＧＦＲ表达呈正相关，而与ｃ－ｅｒｂＢ－２呈负相关。（４）ｐ５３表达与其它基因表达无明显关系。上述结果表明，胃癌发生发展过程中伴有多种癌基因的变化，其出现时间不同，意义也不一样。     

C－erbB－2，人表皮生长因子及其受体在大肠癌中表达的意义

用ＡＢＣ免疫组化法测定２００例大肠癌组织中Ｃ－ｅｒｂＢ－２，人表皮生长因子（ｈＥＧＦ）及其受体（ＥＧＦＲ）。结果发现：１）Ｃ－ｅｒｂＢ－２，ｈＥＧＦ，ＥＧＦＲ在２００例大肠癌中阳性表达分别为３６％、４４％、４７％，三者共同阳性为１６．５％。２）ｈＥＧＦ，ＥＧＦＲ在大肠癌ＤｕｋｅｓＣ、Ｄ期，肿瘤＞２ｃｍ、低分化腺癌，有深度浸润和淋巴结转移者阳性率显著高于其它各型（Ｐ＜０．０１）。３）Ｃ－ｅｒｂＢ－２，ｈＥＧＦ和ＥＧＦＲ阳性病例存活率明显低于这些阴性病例（Ｐ＜０．０１）。结果表明，Ｃ－ｅｒｂＢ－２，ｈＥＧＦ和ＥＧＦＲ在大肠癌的侵袭性生长中起重要作用，ｈＥＧＦ和ＥＧＦＲ可作为大肠癌患者高度恶性的生物学指标。     

表皮生长因子受体,c—erbB—2在脑星形细胞瘤中的表达

应用免疫组织化学方法对４５例原发性脑星形细胞瘤石蜡包埋标本进行ｃ－ｅｒｂＢ－１表达产物表皮生长因子受体（ＣＥＧＦＲ）以及ｃ－ｅｒｂＢ－２表达产物进行检测，结果表明：ＥＧＦＲ以及ｃ－ｅｒｂＢ－２在高级别星形细胞瘤中的表达阳性率（分别为７２％、５６％）均显著高于低级别星形细胞瘤（分别为２５％、１５％，Ｐ＜０．０１），且两者表达呈相关性（Ｐ＜０．０５）。提示ＥＧＦＲ、ｃ－ｅｒｂＢ－２在星形细胞瘤中的表达与肿瘤病理分级有潜在关系，两者的表达不是相互独立的，且ｃ－ｅｒｂＢ－２表达可能仅限于那些有高水平ＥＧＦＲ表达的肿瘤细胞中     

乳腺肿瘤雌、孕激素受体表达与细胞增殖

目的：观察乳腺肿瘤雌、孕激素受体表达与细胞增殖的关系。方法：用免疫细胞化学技术（ＡＢＣ法）对经病理确诊２５５例恶性和６６０例良性乳腺肿瘤进行了ＥＲ、ＰＲ、ｃ－ｅｒｂＢ－２、ｐ５３基因蛋白表达和Ｋｉ－６７抗原检测。结果：良、恶性乳腺肿瘤间,ＥＲ、ＰＲ阳性率均有极显著差异。良性肿瘤组中,ＥＲ＋ＰＲ＋组和ＥＲ－ＰＲ－组间差异有显著性;ｐ５３表达率在ＥＲ、ＰＲ阴、阳性组间差异有显著性;ｃ－ｅｒｂＢ－２表达     

胃癌组织中p53、c-erbB-2、EGFR、nm23、E-cadherin基因表达及预后价值

寻找胃癌临床病理特征和预后的可靠性分子指标,建立一种能被临床普遍应用的简易方法。方法：应用免疫组化法检测了具有随 １７１例胃癌标本中ｐ５３、ｎｍ２３、ｃ－ｅｒｂＢ－２、ＥＧＦＲ和Ｅ－钙粘蛋白（Ｅ－ｃａｄｈｅｒｉｎ,简写为Ｅ－ｃａｄ）的表达。结果：（１）Ｃｏｘ比例风险模型多因素分析表明,ｐ５３,ｃ－ｅｒｂＢ－２,ＥＧＦＲ和Ｅ－ｃａｄ是影响胃癌预后的因子;ｐ５３、ｃ－ｅｒｂＢ－２及ＥＧＦＲ表达的胃癌病     

胃癌雌激素受体和c—erbB—2表达的关系及意义

目的 探讨胃癌雌激素受体（ＥＲ）和ｃ－ｅｒｂＢ－２癌的基因的相互关系临床意义。方法 采用ＡＢＣ免疫组化方法分别检测了８１例胃癌组织中的雌激素受体和ｃ－ｅｒｂＢ－２。结果 在ＥＲ阳性病例中，ｃ－ｅｒｂＢ－２的阳性率高（５０％）。在ＥＲ阴性的病例中，ｃ－ｅｒｂＢ－２的阳性率低（３０．９％）。ＥＲ和ｃ－ｅｒｂＢ－２共同表达阳性者的淋巴结转移率（９２．３１％）明显高于两者共同表达阴性者（５０％）（Ｐ〈０．     

PCNA、C-erbB－_2、ER和PR检测在乳腺癌中的意义

本文用ＡＢＣ法对乳腺癌和乳腺良性病变的组织进行ＰＣＮＡ、Ｃ－ｅｒｂＢ－２、ＥＲ和ＰＲ检测。１５例乳腺癌中ＰＣＮＡ均为阳性，Ｃ－ｅｒｂＢ－２８例阳性，ＥＲ１１例阳性，ＰＲ６例阳性。１５例良性病变中，ＰＣＮＡ２例阳性，Ｃ－ｅｒｂＢ－２２例阳性。ＰＣＮＡ和Ｃ－ｅｒｂＢ－２在良恶性乳腺组织的表达，经统计学Ｘ￣２检验有显著意义（Ｐ＜０．０１）。指出ＰＣＮＡ和Ｃ－ｅｒｂＢ－２可反映细胞增殖情况，与临床病理结合可帮助乳癌的早期诊断和预后估价。为对患者的综合治疗提供理论依据。     

ER,EGFR,p53在乳腺癌组织中的比较研究

采用免疫组化染色技术,检测７５例原发乳腺癌组织中雌激素受体（ＥＲ）,表皮生长因子受体（ＥＧＦＲ）及ｐ５３的表达。结果表明：ＥＲ、ＥＧＦＲ、ｐ５３的阳性表达率分别为４９．３％、４１．３％和３７．３％。ＥＲ、ＥＧＦＲ的表达与腋淋巴结转移、临床分期有明显相关性（Ｐ＜０．０５）;与年龄及肿瘤大小无明显相关性（Ｐ＞０．０５）。ＥＧＦＲ与ＥＲ有负相关性（Ｐ＜０．０５）。在有４个以上腋淋巴结转移的２１例病例中,ＥＧＦＲ阳性者１４例,占６６．７％。２０例临床Ⅲ期的病例,ＥＧＦＲ阳性者１５例,占７５．０％。ｐ５３的表达与腋淋巴结转移、临床分期、年龄及肿瘤大小均无明显相关性（Ｐ＞０．０５）;与ＥＲ呈负相关性（Ｐ＜０．０５）;与ＥＧＦＲ呈正相关性（Ｐ＜０．０５）。研究认为ＥＧＦＲ蛋白表达阳性的乳腺癌病人预后不良,ｐ５３蛋白表达阳性与乳腺癌病人的预后无明显相关性。     

乳腺癌组织中nm23、c-erbB-2、p53表达与临床病理特征的关系

目的　研究乳腺癌组织中nm 2 3、c erbB 2、p5 3基因蛋白的表达与临床病理特征的关系。方法　采用免疫组化S -P法 ,分别检测 76例乳腺癌、10例乳腺良性病变组织中nm 2 3、c erbB 2、p5 3基因蛋白的表达。 结果　c erbB 2、p5 3蛋白在乳腺良恶性病变之间的表达率有显著性差异 (P <0 .0 5 ,P <0 .0 1)。nm 2 3、c erbB 2蛋白表达与乳腺癌的组织学分级有关 (P <0 .0 5 ,P <0 .0 1)。 3种基因蛋白的表达均与腋窝淋巴结转移相关 (P <0 .0 1) ,与乳腺癌的组织学类型、患者年龄及肿瘤大小无关 (P >0 .0 5 )。在乳腺癌组织中 ,nm 2 3与c erbB 2、nm 2 3与 p5 3的表达呈均负相关 (P <0 .0 1,P <0 .0 5 ) ,c erbB 2与p5 3的表达则呈正相关 (P <0 .0 5 )。结论　nm 2 3、c erbB 2、p5 3基因参与乳腺癌的发生发展过程。联合检测nm 2 3、c erbB 2、p5 3基因蛋白对预测乳腺癌淋巴结转移及判断预后有重要意义     

c-erbB-2 and the “triple-state” in early breast carcinomas

Although c-erbB-2 expression is, in general terms, an ominous prognostic indicator in breast carcinomas, there are suggestions that lack of this oncogene, when combined with analogous lack of estrogen (ER negative) and progesterone receptors (PgR negative)—“triple-negative phenotype”, is linked with an equally poor prognosis. We investigated this hypothesis in a series of early ductal breast carcinomas. A total of 116 specimens with early breast cancer, defined as tumors of ≤2 cm in size and clinically negative axilla, were studied immunohistochemically for ER, PgR, and c-erbB-2 expression. The median follow-up was 131 months (range 62–245 months). ER positive tumors had a favorable clinical course, compared to ER negative neoplasms, but only for the first 10 years of follow-up (P = 0.04). Prognosis was poorer for the PgR negative cases, relative to PgR positive tumors (P = 0.005), but this stood true for the entire investigation period. Triple-negative breast carcinomas had a poor prognosis, while triple-positive tumors had a favorable outcome. However, if triple-positive and triple-negative cases were excluded from the original sample, the remaining c-erbB-2 positive cases were connected with poor prognosis, relative to the remaining c-erbB-2 negative tumors. c-erbB-2 oncogene has a complex biological role in early breast carcinomas for its expression characterizes subgroups of patients with both favorable (triple-positive phenotype) and unfavorable prognosis (c-erb-B2 positive cases after excluding triple-positive and triple-negative tumors)—a phenomenon presumably due to activation of different biological pathways. Elucidation of these pathways may determine subgroups of patients with tumors requiring different targeted agents.     

c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues

BACKGROUND AND OBJECTIVES: We investigated whether expression levels of c-erbB-2 and p53 proteins in breast cancer tissues differ in primary and metastatic lesions. METHODS: Immunohistochemical staining or sandwich enzyme immunoassay was used to determine expression levels of c-erbB-2 and p53 proteins in 42 breast cancer samples from 21 patients. Estrogen (ER) and progesterone receptors (PgR) were also measured by enzyme immunoassay in each case. All patients had undergone radical surgery for primary tumors and surgical resection of asynchronous metastatic lesions. Thirteen patients (62%) were premenopausal and 14 (67%) received postoperative adjuvant therapies. Median disease-free survival time was 26 months (range, 5-104). The resected metastatic lesions included 1 in the liver, 3 in the lung, and 3 in the supraclavicular lymph nodes. The remaining 14 were local skin lesions. RESULTS: There was no difference in the positivity rate of c-erbB-2 (38%: 8/21) and p53 (39%: 7/18) expression between the primary tumors and the recurrent lesions. In addition, no discordant c-erbB-2 or p53 expression was observed between the primary tumors and their respective metastatic lesions. Positivity rates for ER and PgR were 50% (10/20) and 60% (12/20) for the primary tumors, but only 25% (5/20) and 30% (6/20) for the recurrent lesions, respectively (P = 0. 19 for ER and P = 0.11 for PgR). CONCLUSIONS: c-erbB-2 and p53 expression levels in breast cancer cells were almost unchanged as the disease progressed and/or in response to adjuvant therapies, regardless of the hormone receptor status.     

THE EXPRESSION OF CATHEPSIN－D，C－erbB－2 AND EGFR IN BREAST CANCER AND ITS CORRELATION TO LYMPHATIC ME

ＴＨＥＥＸＰＲＥＳＳＩＯＮＯＦＣＡＴＨＥＰＳＩＮ－Ｄ，Ｃ－ｅｒｂＢ－２ＡＮＤＥＧＦＲＩＮ　ＢＲＥＡＳＴＣＡＮＣＥＲＡＮＤＩＴＳＣＯＲＲＥＬＡＴＩＯＮＴＯＬＹＭＰＨＡＴＩＣＭＥＴＡＳＴＡＳＩＳＸｕＬｉａｎｇｚｈｏｎｇ许良中；ＺｈｕＷｅｉｐｉｎｇ朱伟萍；...     

新鲜乳腺疾病组织C－erbB－2基因蛋白表达、癌胚抗原、性激素受体的研究

应用ＡＢＣ法对４２例乳腺癌、４０例乳腺良性病变新鲜冰冻组织进行了Ｃ－ｅｒｂＢ－２基因蛋白表达的研究，比较了Ｃ－ｅｒｂＢ－２、雌激素受体（ＥＲ）、孕激素受体（ＰｇＲ）、癌胚抗原（ＣＥＡ）在乳腺癌组织中的表达。结果：乳腺癌中２６例（６１．９％）有Ｃ－ｅｒｂＢ－２基因表达，强阳性表达８例（１９．０％），良性乳腺病变也有表达；淋巴结转移多见于Ｃ－ｅｒｂＢ－２阳性、ＥＲ阴性，ＣＥＡ阴性病例；随着Ｃ－ｅｒｂＢ－２表达程度增加（－→＋→＋＋），淋巴结转移阳性率增加，临床分期为Ｉ期的患者数减少，ＩＩ、ＩＩＩ期增多，ＥＲ、ＰｇＲ受体水平下降。提示，Ｃ－ｅｒｂＢ－２基因蛋白表达与预后有关，表达强度越高，预后越差。     

Pyrimidine nucleoside phosphorylase-activity and biological characteristics of breast-cancer

We investigated whether Pyrimidine nucleoside phosphorylase (PyNPase) activity in breast cancer tissue correlated with biological characteristics of breast cancer. PyNPase activity, ER, PgR, EGFR, DNA ploidy pattern, PCNA positive cells and amplification of the c-erbB-2 gene were determined in specimens from 138 patients. PyNPase activity was significantly higher in ER negative than ER positive carcinomas (p<0.05), in PgR negative than PgR positive carcinomas (p<0.05) and significantly higher in tumors with c-erbB-2 gene amplification compared with tumors with no amplification (p<0.05). The results suggest that PyNPase activity in breast cancer tissue may be a new biological characteristic of breast cancer.     

Prognostic value of estrogen receptor status can be improved by combined evaluation of p53, Bcl2 and PgR expression: an immunohistochemical study on breast carcinoma with long-term follow-up

Steroid receptor analysis is the only widely accepted prognostic/predictive marker in breast cancer (BC) treatment. In the present study we evaluated the prognostic role of ER/PgR with p53 and Bcl2, in a series of 277 BC (153 pN1/2, 122 pNO, 2 pNx) with a long-term follow-up (67 months for DFS, 75 months for OS). Our results, besides confirming the usefulness of ER immunohistochemical expression as a prognostic marker, showed that PgR expression alone had a borderline/not significant prognostic value in the whole series (p=0.08 for DFS and p=0.09 for OS), while showed to be prognostic in N+ cases (p=0.02 for DFS and p=0.03 for OS). PgR prognostic value, however, was not independent at the multivariate analysis. By combining ER with PgR, p53 and Bcl2, we showed that ER/p53 and ER/Bcl2 phenotypes had a better discriminant role than ER/PgR phenotype. The ER+/p53+ phenotype was at higher risk of relapse/death as compared with ER+/p53- phenotype. Conversely ER-/p53+ phenotype showed the most unfavourable prognosis. Similar results could be observed concerning ER/Bcl2 phenotypes. Our study showed that the combined evaluation of ER/PgR weakly enhanced the prognostic/predictive power of ER status alone. On the contrary, the combined evaluation of ER/p53 and ER/Bcl2, improved this prognostic/predictive capability and allowed the separation of ER positive and ER negative cases into subgroups with different prognosis.     

ER、PR 及 C-erbB-2、p53 在 87 例甲状腺癌中的表达及临床意义

目的：检测甲状腺癌中ER、PR及C—erbB-2，r63的表达并探讨它们的临床意义。方法：应用免疫组化S—P法对87例甲状腺癌、20例腺瘤、20例瘤旁甲状腺组织进行ER、PR、C—erbB-2、p53的检测。结果：甲状腺癌中ER、PR的阳性表达率分别为64．4％和63．2％，均与细胞分化程度，组织学类型有关，但与年龄，性别无关。无淋巴结转移组的甲状腺癌ER、PR阳性率为75．4％和70．5％，显著高于有转移组的53．8％和46．2％（P〈0．05）。C—erbB-2表达随癌组织分化程度增高而增高，p53表达随癌组织分化程度增高而减少，与C—erbB-2间呈负相关。在淋巴结转移组中C—erbB-2阳性率增高明显（P〈0．01）。结论：ER，PR，C—erbB-2，p53可作为甲状腺癌分化及恶性程度的评价指标，并且能反映预后。