组蛋白酶和c-erbB-2在乳腺癌中的表达

目的探讨乳腺癌病人c-erbB．2和cath-D表达与临床病理及预后的关系。方法通过免疫组化法，检测128例乳腺癌病人的c-erbB-2和cath-D的表达。结果cath-D和c-erbB-2表达与肿块大小、淋巴结转移显著相关（P〈0．0001）。c-erbB-2表达比不表达病人预后差（P=0．01）。结论c-erbB-2阳性表达和cath-D阳性表达者，恶性程度高，易转移、预后差。     

乳腺癌患者EB病毒感染与癌基因c-erbB-2相关性的研究

目的：探讨乳腺癌患者EB病毒（Epstein—Barr virus，EBV）感染与癌基因c—erbB-2相关性。方法：原位杂交法检测乳腺癌患者癌组织及相应癌旁组织石蜡标本中EBV编码的小RNA（EBER1）；免疫组化法检测EBV阳性乳腺癌及EBV阴性乳腺癌标本癌基因c—erbB-2的表达状况。结果：180例乳腺癌患者癌组织标本中检测到17例EBER1表达，阳性率为9．4％；而相应癌旁组织中均未检测到EBV感染，二者差异有显著性（P〈0．05）。EBV阳性乳腺癌组c—erbB-2蛋白表达显著高于EBV阴性（P〈0．01）。结论：部分乳腺癌患者EB病毒感染与癌基因c—erbB-2有-定的相关性。     

EGFR／HER1和C—erbB-2／HER2在乳腺癌表达的意义及其相关性

目的：探讨乳腺癌中EGFR和C—erbB-2基因蛋白表达的临床意义。方法：乳腺癌86例，乳腺腺瘤36例，采用免疫组织化学方法，检测EGFR／HER。和C—erbB-2／HER：阳性率，分析它们的相关性。结果：EGFR和C—erbB-2在乳腺癌中的表达高度正相关（r=0、73）。它们在乳腺癌中的阳性率明显高于腺瘤（P〈0．001）。在乳腺癌中EGFR和C—erbB-2的阳性率分别为56．98％（49／86）和70．93％（61／86），差异无显著性（P〉0．05）。在浸润癌和有淋巴结转移组阳性率高于非浸润组和无淋巴结转移组（P〈0．001）。结论：EGFR和C—erbB-2在乳腺癌发生中有协同作用，是预后不良的指标。     

c-erbB-2和nm23蛋白在乳腺癌中的表达及其临床意义

目的：探讨c-erbB-2和nm23在乳腺癌中的表达及其与临床预后因素的关系。方法：采用免疫组织化学S-P法检测70例原发性乳腺癌c-erbB-2和nm23蛋白表达,分析其表达水平与乳腺癌病理参数的关系。结果：c-erbB-2蛋白的阳性表达率为45．7％,与年龄、肿瘤大小无明显相关（P〉0．05）,与腋淋巴结转移及临床分期呈明显正相关（P〈0．05）。在组织学分级的比较中,高分化患者阳性率低,中低分化患者c-erbB-2蛋白表达阳性率高,有显著性差异（P〈0．05）,但中低分化患者之间无明显差异（P〉0．05）。nm23蛋白的阳性表达率为68．6％,与临床分期、组织学分级及腋淋巴结转移呈显著负相关,与年龄及肿瘤大小无明显关系。c-erbB-2表达与nm23表达两者之间呈明显负相关（P〈0．05）。结论：联合检测乳腺癌组织中c-erbB-2和nm23表达来估计患者预后指导意义更佳。     

EGFR/HER1和C-erb B-2/HER2在乳腺癌表达的意义及其相关性

目的：探讨乳腺癌中EGFR和C—erbB-2基因蛋白表达的临床意义。方法：乳腺癌86例，乳腺腺瘤36例，采用免疫组织化学方法，检测EGFR／HER。和C—erbB-2／HER：阳性率，分析它们的相关性。结果：EGFR和C—erbB-2在乳腺癌中的表达高度正相关（r=0、73）。它们在乳腺癌中的阳性率明显高于腺瘤（P〈0．001）。在乳腺癌中EGFR和C—erbB-2的阳性率分别为56．98％（49／86）和70．93％（61／86），差异无显著性（P〉0．05）。在浸润癌和有淋巴结转移组阳性率高于非浸润组和无淋巴结转移组（P〈0．001）。结论：EGFR和C—erbB-2在乳腺癌发生中有协同作用，是预后不良的指标。     

ER、PR及C-erbB-2表达与乳腺癌临床病理特征及其预后的关系

目的探讨ER、PR、C—erbB-2表达与乳腺癌临床病理特征及其预后的关系。方法采用免疫组化方法,对1568例乳腺癌患者进行ER、PR、C—erbB-2检测,并分析其与患者年龄、家族史、肿瘤体积、淋巴结转移数目、病理类型、组织学分级及预后患者的关系。结果C—erbB-2表达阳性组患者具有年龄较小（P=0．001）、肿瘤体积较大（P=0．001）、组织学分级较差（P=0．002）、淋巴结转移数目较多（P：0．001）、预后较差（P：0．001）等特点;ER,PR,C—erbB-2表达均阴性的患者预后也较差。结论激素受体及C—erbB-2表达水平可作为制定乳腺癌治疗方案的重要参考指标。     

C-erbB-2、p53、ER和PR受体在乳腺癌组织中的表达及意义

目的分析研究C—erbB-2、p53、ER、PR在乳腺癌中的表达与分期、转移关系及临床意义。方法用免疫组化法测定83例原发性乳腺癌C—erbB．2、p53、ER、PR的表达情况,进行对照比较。结果C—erbB-2、p53、ER、PR阳性表达者分别为30例（36．1％）、31例（37．3％）、45例（54．2％）、53例（63．9％）。C—erbB-2的表达与p53呈正相关（P〈0．05）,与ER、PR呈负相关（P〈0．05）。C—erbB-2和p53的表达率随着临床分期增加和淋巴结转移而增加,差异有显著性（P〈0．05）。ER、PR阳性表达率随着临床分期的递增和淋巴结转移的减少而降低,差异无显著性（P〉0．05）。ER、PR阳性表达率与C．erbB-2、p53表达呈负相关,差异无显著性（P〉0．05）。结论C—erbB-2、p53是判断乳腺癌预后的有效指标,ER、PR与临床分期及腋窝淋巴结转移有一定关系,联合检测C-erbB-2、p53、ER、PR可指导临床综合治疗。     

BCSG1 survivin在浸润性乳腺癌中的表达及预后相关性的研究

目的：探讨BCSG1、surivin蛋白在浸润性乳腺癌中表达的意义及其相关性。方法：采用免疫组化SP法检测100例浸润性乳腺癌组织中BCSG1、surivin蛋白的表达情况，同时取10例正常乳腺组织作对照。结果：BCSG1、survivin在浸润性乳腺癌中阳性表达分别为65％（65／100）、67％（67／100），二者在浸润性乳腺癌中的表达存在着明显的相关性（r=0．288。P〈0．01），进一步发现共表达率达到50％，明显高于c-erhB-2的阳性率，BCSG1、survivin共表达和共表达阴性且c-erbB-2阴性的两组病例淋巴结转移情况分别为86．4％（19／22）和17．6％（3／17），有显著性差异（P〈0．01）。结论：在c-erbB-2阴性表达乳腺癌病例中，BCSG1、survivin共阳性表达者淋巴结转移率明显高于BCSG1和survivin均呈阴性表达者，BCSG1、survivin的共表达可能是不好的预后因素。因此，同时检测BCSG1、survivin和c-erbB-2的表达对乳腺癌生物学行为的判定可能更有价值。     

Galectin-3表达与乳腺癌进展、转移关系的研究

目的研究galectin-3表达与乳腺癌进展及淋巴结转移的关系。方法应用组织芯片技术和免疫组织化学方法对117例浸润性乳腺癌和41例乳腺良性病变（乳腺纤维腺瘤及乳腺小叶增生）的galectin-3表达进行检测。结果Galectin-3在乳腺癌和乳腺良性病变中的阳性率分别为87．61％（99／113）和29．73％（11／37），乳腺癌组galectin-3表达率明显高于乳腺良性病变组（P〈0．001）。乳腺癌中galectin-3阳性表达与淋巴结转移（P〈0．005）、肿瘤低分化（P〈0．05）、ER阴性（P〈0．05）及c-erbB-2阳性表达（P〈0．05）有关，但与TNM分期、患者年龄及PR、E—cadherin表达的关系尚无统计学意义。结论乳腺癌中galectin-3表达可能促进肿瘤演进，并可能增加患者发生淋巴结转移的风险。     

ERβ、C-erbB-2及bcl-2蛋白在乳腺癌组织的表达及意义

目的：检测乳腺癌组织中雌激素受体p（ERp）、C—erbB-2和bcl-2蛋白的表达情况，并分析ERB蛋白的表达与组织学分级、C—erbB-2及bcl-2蛋白表达的关系。方法：采用免疫组化S—P法检测96例乳腺癌组织标本中ERB、C—erbB-2及bcl-2蛋白的表达情况，并作统计学分析。结果：96例乳腺癌组织标本中，ERp、C—erbB-2及bcl-2蛋白阳性表达率分别为64．6％、36．5％和51．0％；ERB蛋白的表达与组织学分级、C—erbB-2蛋白的表达呈负相关（P〈0．05），与bcl-2蛋白的表达呈正相关，与腋淋巴结状态无关（P〉0．05）。结论：ERB蛋白表达可能是乳腺癌患者预后良好的指标。     

C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators.

A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice.     

Prognostic significance of c-erbB-2 and estrogen receptor status in human breast cancer.

Using the 21N polyclonal antibody, we immunohistochemically stained 314 primary breast carcinomas to identify those tumors overexpressing the c-erbB-2 oncoprotein and to ascertain the prognostic significance of this expression on disease-free and overall survival. Positive membrane staining was present in 52 (17%) of these carcinomas of which 7 (13%) were ductal carcinomas in situ. There was no significant relationship between c-erbB-2 positivity and (a) age at diagnosis, (b) menopausal status, (c) tumor size, (d) lymph node status, (e) estrogen receptor status, or (f) whether or not the patient had disseminated disease outside the axillary fields. However, c-erbB-2-positive tumors were significantly associated with poorer grade (P = 0.02). Patients who were positive for this oncoprotein had a shorter disease-free survival (P = 0.002) and reduced overall survival (P = 0.0001). Overexpression of this oncoprotein was predictive of a worse prognosis in lymph node-positive disease (P = 0.003) and in patients presenting with grade II tumors (P = 0.001). Stratifying the patients on the basis of estrogen receptor status suggested that c-erbB-2+/estrogen receptor-negative status was predictive of a poorer prognosis when compared with the other subgroups (P less than 0.001). Primary and recurrent tumor tissues were available from 42 of the 314 patients. Identical patterns of c-erbB-2 expression occurred in 95% of cases, arguing against a direct role for c-erbB-2 expression in the process of tumor dissemination. The high incidence of staining in ductal carcinomas in situ suggests that expression of this oncoprotein is an early event in tumorigenesis. Finally, multivariate analysis indicated that the c-erbB-2 oncoprotein was an independent prognostic indicator for overall survival in breast carcinoma patients.     

The prognostic value of p53 and c-erbB-2 expression, proliferative activity and angiogenesis in node-negative breast carcinoma

AIMS AND BACKGROUND: p53, c-erbB-2 and Ki-67 protein expression and microvessel density (MVD) determined by CD34 antibody were evaluated by immunohistochemistry and their correlation with clinicopathological parameters including estrogen (ER) and progesterone (PR) receptor status and survival were investigated in patients with axillary lymph node-negative infiltrating ductal breast carcinoma. METHODS: The study population consisted of 47 patients with axillary lymph node-negative infiltrating ductal breast carcinoma. RESULTS: p53 and c-erbB-2 expression was detected in 36.2% and 31.9% of patients, respectively. Median Ki-67 expression was 10%. There were no statistically significant differences in the distribution of p53, Ki-67 and c-erbB-2 protein expression in relation to the age of the patients or to the size, histological grade or ER and PR status of the tumors. p53 protein expression correlated positively with c-erbB-2 and Ki-67 protein expression (P < 0.05). The mean MVD was 63.65 +/- 29.1 and it correlated positively with histological grade and Ki-67 expression (P < 0.05). Survival analysis revealed that age, tumor size, p53 and c-erbB-2 expression and PR status had no significant prognostic impact, whereas histological grade, proliferative activity and angiogenic activity were significant prognostic factors. Although ER-positive patients had a statistically significant overall survival advantage, the difference in disease-free survival was not significant. CONCLUSION: In axillary lymph node-negative breast carcinoma the histological grade and the proliferative and angiogenic activity of the tumor could be useful prognostic indicators.     

乳腺癌绝经前后c-erbB-2、ER、PR的表达及与预后的相关性

 目的 探讨乳腺癌绝经前后c-erbB-2、ER、PR受体的表达差异及其与预后的相关性。 方法 回顾性分析432例乳腺癌的病理学资料,其中195例患者随访5年,c-erbB-2、ER、PR的表达采用免疫组化法检测。 结果 （1）绝经前组,c-erbB-2阳性患者的ER阳性率显著低于c-erbB-2阴性患者（P=0.003）;绝经后组,c-erbB-2阳性患者的ER、PR阳性率均显著低于c-erbB-2阴性患者（P＜0.001,P=0.005）。（2）多因素分析显示,绝经前组的独立预后因素为淋巴结转移、c-erbB-2,绝经后组的独立预后因素为淋巴结转移、c-erbB-2和ER。 结论 绝经前与绝经后乳腺癌c-erbB-2、ER、PR受体表达的临床意义有所不同。     

Angiogenesis, p53, and c-erbB-2 immunoreactivity and clinicopathological features in male breast cancer

BACKGROUND AND OBJECTIVES: p53, c-erbB-2, and tumor microvascular density have been shown to be potential prognostic tools in female breast cancer. Our objective was to assess the significance of these biomarkers as prognostic factors in infiltrating male breast cancer. METHODS: A retrospective study of expression of p53, c-erbB-2, and tumor microvascular density was done on a group of 26 male breast cancer patients. Biotin-streptavidin immunohistochemical study with specific anti-p53, anti-c-erbB-2, and anti-CD34 antibodies was carried out on paraffin sections of breast carcinoma. The data of expression of the biomarkers were merged with clinicopathological data such as tumor grade, T class, TNM stage, estrogen receptor status, tumor recurrence, and patient survival. RESULTS: p53 and c-erbB-2 were expressed in 46% and 39% of carcinomas, respectively. No correlation was found between positive immunoreactivity of p53, and tumor grade, size, T class, TNM stage, and survival. Nor was any relation found between tumor size, T class, TNM stage, survival, and c-erbB-2 overexpression. c-erbB-2 overexpression was significantly higher in high grade carcinomas. Estrogen receptor (ER) were positive in 21 out of 26 of tumors (81%). No trends were observed between estrogen receptor status and clinicopathological parameters or survival (data not shown). There was a positive correlation between mean microvascular density (MVD), advanced T class, and survival: higher MVD counts were found in patients with advanced tumors and in those who had tumor relapses or died of metastatic disease. CONCLUSIONS: This study suggests that tumor microvascular density may serve as a potential prognostic tool in male breast carcinoma.     

Expression of C-erbb-2 and epidermal growth-factor receptor in breast-carcinoma - prognostic value and correlation with clinicopathological and biological variables

We examined epidermal growth factor receptor (EGFR) and/or c-erbB-2 expression, clinicopathological variables, silver-stained nuclear organizer region (Ag-NOR) counts, and their prognostic values in 93 patients with operable breast carcinoma. There was no significant correlation between c-erbB-2 and EGFR expression. Increased Ag-NOR counts were significantly associated with positive c-erbB-2 expression, but not with positive EGFR expression. However, co-expression of both proteins was significantly correlated with axillary lymph node metastases. Significant differences in survival were found between groups of patients stratified by tumor size, histological grade, axillary lymph node metastases, c-erbB-2, and EGFR expression by univariate analysis. In addition, c-erbB-2 and EGFR expression in combination was strongly correlated with decreased survival. However, only axillary lymph node metastases and age appeared to be independent prognostic factors by multivariate analysis. We therefore conclude that the prognostic value of c-erbB-2 and EGFR expression is limited in breast carcinoma.     

乳腺癌C—erBb—2、p53、ER和PR表达及意义

目的 分析研究C-erBb-2、p53、ER和PR在乳腺癌中的表达与转移及预后关系。方法用免疫组化法测定192例原发乳腺癌各抗体的表达情况。结果 C-erBb-2阳性率为39.1％(75/192),p53阳性率为32.3％(62/192),ER阳性率为47.9％(92/192),PR阳性率为54.2％(104/192)。C-erBb-2、p53随临床分期的递增和淋巴结转移数目的增多,其阳性表达率随之增加,差异有显著性(P<0.05)。ER和PR的阳性表达率则与C-erBb-2、p53呈负相关,但差异无显著性(P>0.05)。C-erBb-2、p53共同阳性表达与淋巴结转移差异有显著性(P<0.05)。结论 C-erBb-2、p53是判断乳腺癌预后的有效指标。ER、PR与临床分期、淋巴结转移有一定关系,但不十分明显。     

Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme immunoassay

We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay in benign breast disease and primary and recurrent breast cancer and analyzed the relationship between c-erbB-2 protein levels and clinicopathological factors. Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the 13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were significantly different between the stages. Overexpression of c-erbB-2 protein in stages I-IIIB breast cancer was associated with histological grade and serum CEA level, but not with other clinicopathological factors. In addition, there was an inverse correlation in the group of stages I-III plus IV breast cancer between c-erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB-2 protein can be easily determined in the cytosol fraction together with hormonal receptor by this method. The prognostic importance will be evaluated in ongoing adjuvant trials for operable breast cancer patients.      

骨桥蛋白在浸润性乳腺癌中的表达及临床意义

目的研究骨桥蛋白(osteopontin,OPN)在乳腺癌及癌旁组织中的表达及其临床意义。方法收集2006年1月至2007年12月南通大学第二附属医院的87例浸润性乳腺癌组织标本,免疫组织化学法检测OPN、c-erbB-2、ER、PR的表达,分析OPN表达与浸润性乳腺癌患者临床病理特征的关系。结果 47例浸润性导管癌OPN阳性表达率为61.7%,其中在浸润性导管癌Ⅰ级、Ⅱ级、Ⅲ级中OPN阳性表达率分别为33.3%、58.8%、83.3%。浸润性小叶癌OPN阳性表达率38.9%。有、无淋巴结转移组OPN阳性表达率分别是65.9%和39.1%,40例c-erbB-2过表达者中70.0%同时表达OPN。显示OPN表达与乳腺癌组织学分级、淋巴结转移及c-erbB-2表达相关(P<0.05),与患者年龄、肿块大小、组织学类型及ER、PR表达无相关性(P>0.05)。结论 OPN在伴淋巴结转移及c-erbB-2过表达的乳腺癌组织中高表达,可作为乳腺癌预后的评估指标之一。     

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.