乳腺癌c—erbB—2,表皮生长因子受体基因蛋白表达与预后的关系

以免疫组化ＡＢＣ法检测乳腺癌ｃ－ｅｒｂＢ－２、表皮生长因子受体基因蛋白表达，研究其与预后的关系，结果：ｃ－ｅｒｂＢ－２、ＥＧＦＲ阳性表达率各为３８．５％（２５／６５）和４３．１％（２８／６５）。除ＥＧＦＲ表达与ＥＲ、ＰＲ负相关外，ｃ－ｅｒｂＢ－２，ＥＧＦＲ表达与临床预后因素无相关性，二者之间亦无相关性。ｃ－ｅｒｂＢ－２或ＥＧＦＲ阳性组术后生存显著差于阴性组（Ｐ〈０．０１）；多因素分析二者是显著影响     

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。     

表皮生长因子受体及DNA含量在乳腺癌预测因素中的地位

用免疫组化法检测４６例乳腺癌组织中ＥＧＦＲ及ＥＲ，流式细胞技术检测ＤＮＡ倍体状况，结合病理因素及临床随访结果进行分析，结果发现：１）ＥＧＦＲ与ＥＲ呈显著负相关（Ｐ＜０．０５），与肿瘤组织学分级呈显著正相关（Ｐ＜０．０１），不同月经状况、肿瘤大小、淋巴结受累情况及ＴＮＭ分期中ＥＧＦＲ阳性率无显著差异，ＥＧＦＲ阳性患者生存期显著低于ＥＧＦＲ阴性患者的生存期；２）ＤＮＡ含量与ＥＲ呈负相关，与组织学分级，肿瘤大小及ＥＧＦＲ呈显著正相关，ＤＮＡ异倍体患者生存期明显低于二倍体肿瘤患者的生存期（Ｐ＜０．０１）。提示：ＥＧＦＲ、ＤＮＡ可作为乳腺癌预测预后的有效生物学信息。     

83例乳腺癌激素受体和癌胚抗原免疫组化研究

乳腺癌标本８３例，采用ＬＳＡＢ免疫组化法进行雌激素受体、孕激素受体和癌胚抗原检测，阳性率分别为５９％、５４％、８２％。ＥＲ、ＰＲ的阳性表达随着癌组织分化程度的降低及淋巴结转移数目增多而减少，有明显的相关关系（Ｐ＜０．０１）。ＣＥＡ的阳性率在乳腺癌组织分级上呈反相关关系（Ｐ＜０．０１），在淋巴结转移与非转移组中的表达相互比较，有非常显著的差异（Ｐ＜０．０１）。同时进行乳腺癌ＥＲ、ＰＲ和ＣＥＡ检测，对判断肿瘤的恶性程度，估计预后可起到互补的作用。     

乳腺癌p53、c－erbB－2基因蛋白、表皮生长因子受体与雌、孕激素受体的表达及其临床意义

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阳性率在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要标志。     

表皮生长因子受体在肝癌中的表达及其临床意义

对５１例肝癌标本进行的免疫组织化学分析显示，４７％的标本肿瘤细胞中有表皮生长因子受体（ＥＧＦＲ）表达。根据ＥＧＦＲ在肿瘤中的表达情况将病例分为两组，ＥＧＦＲ阳性组和ＥＧＦＲ阴性组。ＥＧＦＲ阳性组的肿瘤体积和术后复发率均高于ＥＧＦＲ阴性组（Ｐ＜０．０５）。两组的肿瘤分化程度无显著性差异。本实验结果说明ＥＧＦＲ在肝癌细胞中的表达与肝癌病人的预后有关     

组织蛋白酶D、c－erbB－2和表皮生长因子受体在乳腺癌组织中的表达及其与淋巴结转移的关系

应用免疫组织化学的方法，对２７７例乳腺癌的组织蛋白酶Ｄ（Ｃａｔｈ－Ｄ）、ｃ－ｅｒｂＢ－２和表皮生长因子受体（ＥＧＦＲ）癌基因蛋白的表达及其与淋巴结转移的关系进行了研究。结果发现，Ｃａｔｈ－Ｄ表达阳性者１０７例（３８．６２％），阴性者１７０例（６１．３８％）。Ｃａｔｈ－Ｄ阳性的乳腺癌有淋巴结转移的占８３．１７％，Ｃａｔｈ－Ｄ阴性的乳腺癌有淋巴结转移的占３７．６４％，两者的差别极为显著（Ｘ￣２＝５５．０５，Ｐ＜０．０００１）。Ｃａｔｈ－Ｄ阳性的乳腺癌中，ｃ－ｅｒｂＢ－２阳性者５６例（５２．３４％）；Ｃａｔｈ－Ｄ阴性的乳腺癌中，ｃ－ｅｒｂＢ－２阳性者２７例（１５．８８％），两者有明显的差别（Ｘ￣２＝４１．５８，Ｐ＜０．０００１）。Ｃａｔｈ－Ｄ阳性的乳腺癌中，ＥＧＦＲ阳性的有４９例（４５．７９％）；Ｃａｔｈ－Ｄ阴性的乳腺癌中，ＥＧＦＲ阳性的仅２４例（１４．１２％），两者的差别亦极为显著（Ｘ￣２＝３３．９５，Ｐ＜０．０００１）。上述结果提示，Ｃａｔｈ－Ｄ阳性的乳腺癌恶性程度高，易转移、预后差。临床对上述病人应提供特别的治疗方案并抓紧随访工作。     

乳腺癌上皮生长因子受体的临床病理观察及预后意义

用免疫组化法检测了８９例乳腺癌的上皮生长因子受体（ＥＧＦＲ）表达状况，并结合其雌激素受体（ＥＲ）表达和ＤＮＡ含量的分析结果，发现乳腺癌ＥＧＦＲ的阳性率为３９．３％，ＥＧＦＲ阳性乳癌中ＥＲ的阳性率为１１．４％（４／３５），而ＥＧＦＲ阴性组中ＥＲ阳性率为７７．８％（４２／５４），两者阳性率的分布状况有显著性差异（Ｐ〈０．０１）；同样，经流式细胞术ＦＣＭ分析，ＥＧＦＲ为阳性的乳癌组异倍体出现率也明显高于     

乳腺癌流式细胞仪分析的临床意义

通过对８６例乳腺癌的ＦＣＭ分析：发现二倍体肿瘤２４例，异倍体６２例。前者ＳＰＦ１６．８±１０．３％，后者ＳＰＦ２２．２±９．８％（Ｐ＜０．０５）。其中进行ＥＲ检查的６４例中发现：ＥＲ阳性组异倍体占６６％，ＥＲ阴性组异倍体占９２．９％（Ｐ＜０．０５）；前者ＳＰＦ１８．１±９．１％，后者ＳＰＦ２６．０±１３．０％（Ｐ＜０．０５）。ＣＥＡ阳性与否与异倍体检出率、ＳＰＦ及ＥＲ阳性率无明显关系。月经状态、腋淋巴结转移与ＦＣＭ检测结果无关系。因此作者认为ＦＣＭ分析可了解肿瘤本身的生物学特性，并可成为新的、独立的预后指标。     

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     

Relationship between epidermal growth factor receptor status and various prognostic factors in human breast cancer

Relationship between epidermal growth factor receptor (EGFR) status and various prognostic factors was investigated in 91 human breast cancer tissues. Epidermal growth factor receptor was measured by biochemical competitive binding assay using iodine 125 epidermal growth factor (125I)-EGF. The EGFR status was not correlated with axillary lymph node involvement, tumor size, stage, and histologic type, but significantly correlated with histologic grading (P less than 0.05) and lymphatic invasion (P less than 0.01). Between EGFR and estrogen receptor (ER) status, a clear inverse relationship was observed (P less than 0.01). The Ki-67-positive stained cell rate, which reveals the proportion of cycling cells, was significantly higher in EGFR-positive tumor tissues than in EGFR-negative cases. Furthermore, preliminary postoperative survey demonstrated a high tendency of recurrence rate of patients with EGFR-positive tumors as compared with those with EGFR-negative tumors. These data suggest that EGFR status may be important for the prediction of biologically high malignant potential.     

乳腺癌nm23基因和雌、孕激素受体表达及其临床意义

[目的]研究nm23基因,雌激素受体(ER)、孕激素受体(PR)在乳腺癌中的表达及临床意义.[方法]应用免疫组化SP法检测60例临床及随访资料完整的乳腺癌患者标本nm23、ER、PR的表达,结合临床表现及随访结果作统计学分析.[结果]nm23、ER、PR阳性表达率分别为60.0%、73.3%、66.7%.nm23阳性表达与临床分期相关(P＜0.05).nm23基因的表达与乳腺癌远处转移及腋淋巴结转移呈显著负相关(P＜0.05),与生存率呈正相关(P＜0.05).ER、PR阳性表达率与年龄、临床分期和淋巴结转移无关(P＞0.05).ER、PR的阳性表达与乳腺癌远处转移呈显著负相关(P＜0.05),与生存率呈正相关(P＜0.05).在判断转移和预后方面,ER( )PR( )与nm23基因阳性表达之间存在着正相关性.[结论]检测乳腺癌组织nm23、ER、PR对评价乳腺癌患者的预后和指导临床治疗有重要价值.     

乳腺癌组织中c-erbB-2、p53、PCNA和nm23蛋白的表达及其临床意义

目的探讨生物学指标c-erbB-2、p53、PCNA和nm23在乳腺癌中的表达及其与临床乳腺癌预后因素的关系.方法应用免疫组织化学方法对1180例乳腺癌组织c-erbB-2、p53、PCNA和nm23的表达进行检测.结果 c-erbB-2表达与患者年龄(≥35岁)、肿瘤临床期别、腋淋巴结状态、组织学分级呈负相关,与雌激素受体(ER)、孕激素受体(PR)呈正相关;p53蛋白表达与患者临床期别、组织学分级、病理类型呈负相关,与腋淋巴结状态呈正相关;PCNA表达与患者临床期别、腋淋巴结状况呈负相关,与ER、PR呈正相关;nm23蛋白表达与患者腋淋巴结状态呈负相关,与病理类型、ER、PR呈正相关.结论生物学指标c-erbB-2、p53、PCNA、nm23与临床期别、组织学分级、腋淋巴结状态及病理类型等联合应用,有助于提高对乳腺癌预后评价的正确性.     

三阴性乳腺癌临床病理特点及与EGFR表达关系的探讨*

目的:研究三阴性乳腺癌的临床病理特点、预后及与EGFR 表达的关系。方法:回顾性分析天津医科大学总医院1997年1 月至2004年1 月200 例乳腺癌患者的临床资料,总结其病理特征及随访结果,并将200 例病例对应的石蜡标本制作成组织芯片,用免疫组织化学法检测乳腺癌组织中ER、PR、HER-2 的表达,进行乳腺癌分子分型。检测EGFR 蛋白的表达,分析其与乳腺癌病理特征及预后的关系。结果:200 例乳腺癌患者中三阴性乳腺癌42例（21.00%）,在患者年龄、肿瘤大小、临床分期、淋巴结状态等病理参数的分析中,三阴性乳腺癌与非三阴性乳腺癌的分布无明显差异,而在绝经状态及肿瘤组织学分级的分析中,三阴性乳腺癌与非三阴性乳腺癌差异有统计学意义（P<0.05）。 三阴性乳腺癌患者中17例死亡（生存率59.52%）,非三阴性患者26例死亡（生存率83.54%）,二者有显著性差异（P<0.05）。 EGFR 在三阴性乳腺癌中表达率较高（69.05%）,与肿瘤组织学分级及淋巴结转移密切相关,且表达EGFR 的三阴性乳腺癌患者生存时间较短。结论:三阴性乳腺癌发病率虽然不高,但其与常规的乳腺癌预后相关因素缺乏特定联系,患者预后差。EGFR 在三阴性乳腺癌中高表达,可作为三阴性乳腺癌的一个重要的预后指标,并为临床提供了治疗的靶点。      

The Case to Case Comparison of Hormone Receptors and HER2 Status between Primary Breast Cancer and Synchronous Axillary Lymph Node Metastasis

Background: Nowadays, the adjuvant treatment for breast cancer patients chosen depends on immunohistochemical pattern of Estrogen receptor(ER), Progesterone receptor(PR) and HER2 status of primary breast tumor. Several retrospective studies showed significant discordance in receptor expression between primary and metastatic tumors. The objective of this research was to determine discordant rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis of individual breast cancer patients in Thammasat University Hospital. Methods: A prospective observational study of all breast cancer patients who have axillary metastasis and underwent surgery at Thammasat Hospital between January 2011 to December 2015. Tumor staging, ER, PR, and HER2 status on primary breast tumor were recorded. Synchronous axillary lymph node metastasis was evaluated with immunohistochemistry for ER, PR, and HER2. Results: The ER-positive rate from primary tumor to synchronous axillary lymph node metastasis decreased from 74.7% to 71.7%; the HER2 overexpression rate was decreased from 26% to 24%. In contrast, PR positive rate were 71% in both primary tumor and synchronous axillary lymph node metastasis. In case to case comparison, discordance rate of ER, PR and HER2 status between primary breast cancer and synchronous axillary lymph node metastasis were 11.1%, 20.2% and 10.1%, respectively. Furthermore, the tumor staging was not significant associated with discordance of ER, PR and HER2. Conclusion: ER, PR and HER 2 biomarkers showed significant concordance between primary tumor and synchronous axillary lymph node metastasis. Hence, if we cannot assess the ER, PR and HER2 status in primary tumor, then synchronous axillary lymph node metastasis can be studied instead. However, the repeat of biomarker testing in node-positive breast cancer patients may be beneficial for tailored adjuvant therapy, especially for patients with negative hormone receptor and/or HER2 profile on primary tumor.     

Correlation of Hormone Receptor and HER2/neu Expression with Clinicopathologic Parameters in Primary Breast Tumors

Background: Breast cancer (BC) is a major health issue worldwide as well as in Pakistan. All women belonging to any race, ethnicity or lineage are in danger of developing breast cancer. Significant factors influencing the development of breast malignancies are the genetic background, environmental conditions, reproductive parameters, the consequences of female hormones both intrinsic and extrinsic, alteration of immune status, and biologic determinants. Materials and Methods: Overall 150 biopsy proven patients were included in the study. Samples were submitted for histopathology and determination of estrogen and progesterone receptor expression and HER2/neu status. Associations with other characteristics like age, tumor stage, node involvement, histological grade were also studied. Results: Mean age at presentation was 46.7 years. The majority had invasive ductal carcinoma, 100 (84.7%), and were in stage pT3, 54 (45.7%). Important relationships (P<0.05) were found among ER, PR positivity, and Her 2 neu overexpression. However, no noteworthy link was identified amongst ER, PR, Her 2 neu and tumor grade, stage, age, lymph node involvement except for the menopausal status. Conclusions: In summary, breast cancer patients featured an advanced stage of disease, more lymph node involvement, and moderately high grade tumors and with more estrogen, progesterone receptor and HER2 positive tumors.     

乳腺浸润性导管癌预后相关因素分析

目的:探讨乳腺浸润性导管癌预后相关因素.方法: 收集130例乳腺浸润性导管癌资料,回顾性分析其临床特征、病理分化程度、复发转移情况、激素受体状况、人类表皮生长因子受体2的表达、临床治疗及生存情况.结果: c-erbB-2表达在ER、PR阳性组低于ER、PR阴性组(P<0.01),ER表达在PR阳性组高于PR阴性组(P<0.01);中、低分化与高分化相比,在淋巴结的转移、肿瘤的转移或复发、临床分期、肿块的大小上,均有统计学差异(P<0.05);单因素分析结果显示,激素受体状况、人类表皮生长因子受体2表达、病理分化程度、淋巴结状况、肿瘤转移或复发、临床分期、肿瘤大小、T分期、N分期、辅助化疗等11个因素与预后相关;多因素分析结果显示:ER状况、病理分化程度、淋巴结状况、临床分期是乳腺浸润性导管癌患者预后的独立影响因素.结论: 对乳腺浸润性导管癌,早期发现并针对病理分化程度及激素受体水平的适当治疗是提高生存期的关键.     

12种凝集素与雌激素和孕激素受体在乳腺癌中的对比研究

本文应用亲和组化法对100例乳腺癌的12种凝集素受体与ER和PR进行对比研究,结果发现:(1)PNA-R与ER阳性符合率91.2％;RCA-R与PR为88.5％。(2)PNA-R与ER,RCA-R与PR在乳腺癌各年龄组、月经状况、肿瘤大小、淋巴结转移和各组织学类型的阳性率呈正相关。(3)PNA-R、ER、RCA-R、PR阳性患者肿瘤的复发率低于阴性患者(P<0.05)。结果提示乳腺癌PNA-R与ER,RCA-R与PR有一致性,可通过亲和组化法对常规石蜡切片测定乳腺癌PNA-R和RCA-R,以推测乳腺癌患者的ER和PR状况,对指导临床估计预后和内分泌治疗有重要意义。     

Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients

Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan–Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR− patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.