乳腺癌组织中褪黑素受体MT1和CUEDC2的表达及临床意义

目的 检测乳腺癌组织中褪黑素受体（MT1）与CUE结构域蛋白2（CUEDC2）的表达,探讨二者表达的相关性及临床意义。方法 采用Western blotting和免疫组化SP法检测80例乳腺浸润性导管癌、30例乳腺导管内癌和30例正常乳腺组织中MT1和CUEDC2的表达情况。结果MT1在乳腺浸润性导管癌、乳腺导管内癌、正常乳腺组织中的阳性表达率分别为788％、60.0％和16.7％,三者差异有统计学意义（P＜0.05）;CUEDC2在乳腺浸润性导管癌、乳腺导管内癌的阳性表达率分别为68.8％、53.3％,明显高于正常乳腺组织的13.3％,差异有统计学意义（P＜0.05）。Western bloting半定量检测显示,乳腺浸润性导管癌MT1和CUEDC2表达分别为0.542±0.078和0.461±0.057,均高于正常乳腺组织（P＜0.05）。MT1和CUEDC2表达与乳腺浸润性导管癌患者有无淋巴结转移（P=0.034,P=0.027）和组织学分级（P=0.018,P=0.022）均有关, 但与年龄和肿瘤大小无关（P＞0.05）。乳腺浸润性导管癌中MT1表达与CUEDC2表达呈正相关（r=0.441,P＜0.05）。结论 MT1和CUEDC2高表达与乳腺癌的发生、发展及转移有关,联合检测二者表达可为乳腺癌基因治疗寻找新的干预靶点提供实验依据。     

乳腺癌临床病理特点与ER、PR的关系

目的探讨乳腺癌临床病理特点与雌激素受体(ER)、孕激素受体(PR)表达的关系。方法回顾性分析120例乳腺癌患者的临床病理特点,应用免疫组化Elivision法测定乳腺癌组织中ER、PR的表达,并分析临床病理特点与ER、PR表达的关系。结果乳腺癌多发于31～50岁(41.7%)及51～70岁(47.5%);最常见肿瘤类型为浸润性导管癌(78.3%);45.8%患者确诊时已有淋巴结转移;Ⅰ级浸润性导管癌占8.5%,Ⅱ～Ⅲ级占91.5%;ER、PR阴性表达率分别为47.5%、59.2%。Ⅰ级浸润性导管癌ER、PR的阴性表达率均低于Ⅱ～Ⅲ级浸润性导管癌,但差异无统计学意义(P>0.05)。Ⅰ级浸润性导管癌中无一例有脉管内瘤栓和淋巴结转移,而Ⅱ～Ⅲ级浸润性导管癌中脉管内瘤栓和淋巴结转移率分别为(34.9%)和(58.1%)(P<0.01)。结论乳腺癌中ER、PR阴性表达的比例近50%;ER阴性表达与高组织学分级有关;ER阴性表达、高组织学分级易导致淋巴结转移。     

乳腺增生与乳腺癌组织中雌激素受体、孕激素受体的表达差异及其临床意义

 目的　探讨乳腺增生及乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）的表达差异及其临床意义。方法　采用免疫组织化学方法检测68例乳腺增生和168例乳腺癌标本中ER、PR的表达。结果　 乳腺癌患者ER表达水平明显高于乳腺增生患者（P＜0.05）,而PR在两组中的表达差异无统计学意义。绝经后乳腺癌患者ER表达水平中位值为30 %,明显高于绝经后乳腺增生患者的10 %（P＜0.05）,而在绝经前两组患者ER表达水平差异无统计学意义。浸润性小叶癌组织内PR的表达明显高于浸润性导管癌等其他类型,差异有统计学意义（P＝0.005）。结论　ER、PR的表达能够较好地反映乳腺疾病的病理生物学特征。     

乳腺浸润性导管癌组织Bmi-1的表达及其临床意义

目的:探讨Bmi-1在乳腺浸润性导管癌组织中的表达及其与临床病理特征的关系。方法:免疫组化法检测84例乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、c-erbB-2和B细胞特异性莫洛尼小鼠白血病病毒整合位点-1(Bmi-1)表达,并取其中43例(51.2%)乳腺癌新鲜肿瘤组织和癌旁的正常组织,采用RT-PCR方法检测其Bmi-1表达。结果:84例乳腺浸润性导管癌组织中Bmi-1蛋白阳性表达率为56.0%(47/84)。43例乳腺癌新鲜肿瘤组织中Bmi-1mRNA阳性表达率为67.4%(29/43)。Bmi-1过表达与临床晚期及ER阴性表达显著相关,P<0.05。Bmi-1表达与患者年龄、肿瘤大小、组织学分级以及PR、c-erbB-2表达均无明显相关性,P>0.05。Bmi-1在乳腺浸润性导管癌与癌旁正常组织中的表达差异有统计学意义,P<0.01。结论:Bmi-1过表达与乳腺浸润性导管癌的发生、发展有关。Bmi-1可能成为预测乳腺浸润性导管癌临床分期的新分子标志。     

FGFR1在乳腺癌分子亚型中的表达及意义

目的 探讨成纤维细胞生长因子受体1(fibroblast growth factor receptor 1,FGFR1)在乳腺癌组织及正常组织中的表达及与雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、谷胱甘肽-S转移酶-π(GST-π)、拓扑异构酶Ⅱα(TOPOⅡα)间的关系.方法 采用免疫组织化学S-P法检测88例乳腺浸润性导管癌和30例正常乳腺组织中FGFR1的表达情况.结果 FGFR1在浸润性导管癌及正常乳腺组织中的表达率分别为37.5％、10.0％,两者间差异有统计学意义(P＜0.05);FGFR1在GST-π阳性及阴性乳腺浸润性癌患者中表达率分别为60.4％、10.0％,差异有统计学意义(P＜0.05).FGFR1在TOPOⅡα阳性及阴性乳腺癌患者中表达率分别为47.2％、22.9％,差异有统计学意义(P＜0.05).FGFR1在Luminal A型、Luminal B型、HER2过表达型、Basal-like型中表达率分别为25.0％、35.3％、56.3％、63.6％,FGFR1表达率在Luminal A和HER2过表达型、Luminal A和Basal-like型间差异有统计学意义(P＜0.05)外,其他各组表达率间差异均无统计学意义(P＞0.05).FGFR1与ER、PR、HER2状态无相关性(P＞0.05),但FGFR1与内分泌治疗耐药呈正相关(P＜0.05).结论 FGFR1在浸润性导管癌的不同分子分型中表达有差异,可能成为预测乳腺癌预后的重要指标之一.     

乳腺浸润性导管癌中Clusterin蛋白表达及其与临床病理特征的关系

[目的]探讨细胞凋亡抑制因子Clusterin在乳腺浸润性导管癌组织中的表达及其与临床病理因素的关系。[方法]应用免疫组化SP法检测70例乳腺浸润性导管癌、20例乳腺增生和10例乳腺癌旁组织标本中Clusterin的表达情况。[结果]Clusterin在乳腺癌旁正常组织、乳腺增生及乳腺浸润性导管癌组织中的阳性表达率分别为0、20.0%及71.4%,乳腺浸润性导管癌组织中的Clusterin表达水平明显高于乳腺增生及乳腺癌旁正常组织(P<0.05)。Clusterin蛋白在乳腺浸润性导管癌中的表达与临床分期、组织学分级及淋巴结转移情况有关(P<0.05),而与患者年龄、肿瘤大小无关(P>0.05)。在乳腺浸润性导管癌组织中Clusterin与ER、PR的表达呈负相关(P<0.05)。[结论]Clusterin可能在乳腺癌的发生发展中发挥重要促进作用,可望成为乳腺浸润性导管癌诊断中的标志物及新的治疗靶点。     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

ER、PR、Her-2在乳腺癌中的表达

目的 探讨乳腺癌组织中雌激素受体(ER)、孕激素受体(PR)、人类表皮生长因子受体-2(Her-2)的表达与临床特征的关系.方法 用免疫组织化学法检测311例乳腺癌组织中ER、PR、Her-2的表达.结果 311例乳腺癌组织中Her-2阳性表达明显低于ER和PR,分别为87例(27.97%)、185例(59.49%)和195例(62.70%).与非浸润性乳腺癌相比,ER、PR在浸润性乳腺癌中的表达明显减少(P<0.05).ER的表达随乳腺癌TNM分期增加而减少(P<0.05),而PR和Her-2的表达与TNM分期无关(P0.05).与无腋窝淋巴结转移者相比,有腋窝淋巴结转移的乳腺癌组织中ER表达明显减少,Her-2表达明显增加(P<0.05).结论 ER、PR、Her-2与乳腺癌的临床特征密切相关,其可能参与乳腺痛的生物学行为调控,常规检测ER、PR、Her-2的表达可为乳腺癌治疗提供依据.     

The effect of estrogen usage on the subsequent hormone receptor status of primary breast cancer

In order to determine if prior use of exogenous estrogens was related to the estrogen receptor (ER) content of primary breast cancers, a retrospective analysis was performed from 536 patients with invasive breast cancer. The patient's age, menopausal status, oral contraceptive or estrogen replacement therapy usage, and the ER and progesterone receptor (PR) content of the breast cancer were recorded for all patients. Hormone usage in premenopausal and postmenopausal patients was compared to ER and PR levels in primary breast cancers using nonparametric testing. Complete information was available from 508 (193 premenopausal and 315 postmenopausal) patients. Breast cancers were ER positive in 72% of postmenopausal patients and 57% of premenopausal patients. The majority of patients received 'Some' form of hormone therapy (111 of 193 premenopausal patients and 233 of 315 postmenopausal patients). Significantly more estrogen receptors were detected in tumors from patients receiving 'some' estrogen therapy compared to 'never' users. Postmenopausal patients 'never receiving estrogen therapy had a lower rate of ER positive tumors (62%) compared to 'some' users (75% ²=4.99, p<0.05). The same relationship was seen for PR ('never' users 44% positive, 'some' users 58% positive, ²=5.19, p<0.05). We conclude that postmenopausal patients who received 'some' estrogen therapy are more likely to have breast cancers that are estrogen receptor and progesterone receptor positive.     

Comparison of ER,PR & HER-2/neu (C-erb B 2) Reactivity Pattern with Histologic Grade,Tumor Size and Lymph Node Status in Breast Cancer

Introduction: Carcinoma of the breast is the most common malignancy of women in Karachi. The currentstudy was conducted with the objective of assessing estrogen receptor (ER), progesterone receptor (PR) andHER-2/neu reactivity patterns of mammary cancers for correlation with histologic grade, tumor size and lymphnode metastasis. Materials and methods: One hundred and fifty modified mastectomy specimens received atthe section of histopathology, Aga Khan University Hospital, were selected using a non-probability samplingmethod. Results: Mean age of the patients was 48.3 years (95%CI 46.5, 50.2). The left breast was more commonlyinvolved (57%). Tumor size ranged from 0.3 to 15.0 cm; 12% were ≤2.0 and 35.3% were ≥ 5.0 cm in diameter.The predominant morphology was infiltrating ductal carcinoma (85.3%). The majority of the cases presentedas grade II (55.3%) lesions with tumor necrosis (70%) and lymph node involvement (71.3%). ER and PR werepositive in 32.7% and 25.3% cases respectively. HER-2/neu was positive (3+) in 24.7%. ER positivity increasedand HER-2/neu positivity decreased with rising age. ER and PR expression was significantly lower in HER-2/neu positive as compared with HER-2/neu negative tumors (ER 83.8% vs 69.8%; PR 91.9% vs 77.8%). In theHER-2/neu positive tumors, ER and PR expression in high grade tumors was significantly decreased comparedwith intermediate grade tumors (ER 5.6% vs 10.5; PR 0% vs 5.3%). ER expression in the HER-2/neu positive,large sized tumors was also significantly decreased compared with smaller tumors (ER 6.3% vs 11.8). Conclusions:ER and PR expression in breast cancers in the current study was found to be comparable to publishedinternational data, but the frequency of HER-2/neu expression was higher, possibly reflecting a young age atdiagnosis. Assessment of prognostic markers for the clinical management of breast cancer patients is stronglyadvocated to provide best therapeutic options.     

Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer

BACKGROUND: The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER+ tumours are less likely HER-2+ and HER-2+ tumours are less likely ER+. METHODS: We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable. Steroid receptors were considered positive for any nuclear staining of invasive cancer cells and for HER-2, either for strong expression by IHC (score 3+) or gene amplification by fluorescence in situ hybridisation (FISH). Based on nonparametric regression, the age-related association between steroid receptors and HER-2 was presented as likelihood curves. RESULTS: The association between ER or PR and HER-2 is age-related. The age-related expression of ER and PR is HER-2 dependent. In HER-2(-) cases, the odds ratio (OR) for being ER+ was 2.594 (95% CI = 1.874-3.591) up to age 50 and age-independent thereafter; for PR-expression the OR was 2.687 (95% CI = 1.780-4.057) up to age 45 and 0.847 (95% CI = 0.761-0.942) thereafter. In HER-2+ cases, the OR was 0.806 (95% CI = 0.656-0.991) to be ER+ and 0.722 (95% CI = 0.589-0.886) to be PR+. The age-related OR for breast cancers to be HER-2+ is steroid receptor dependent. Taking together, ER+PR+HER-2+ breast cancers appear on average 5.4 years earlier than breast cancers of any other ER/PR/HER-2 phenotype (95% CI = 3.3-7.5; P < 0.0001). CONCLUSION: There is a qualitative interaction between age and expression of steroid and HER-2 receptors. Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER+PR+HER-2+ subgroup.     

Steroid receptor status,proliferation and metallothionein expression in primary invasive ductal breast cancers

The most important immunocytochemical prognostic and predictive factors in cases of breast cancer include estrogen receptor alpha (ER) and progesterone receptor (PgR). The present study aimed at examining the relationship between the manifestation intensity of proliferation markers (Ki-67 and nucleolar organizer regions--AgNORs) on one hand, and expression of ER and PgR on the other in a uniform group of invasive ductal breast cancers of G2 grade. Moreover, the study aimed at examining the relationship between the above mentioned markers and expression of metallothionein (MT). The studies were performed on samples of invasive ductal breast cancers of G2 grade, originating from 60 females. In paraffin sections originating from the studied cases immunocytochemical reactions were performed using monoclonal antibodies to ER, PgR, Ki-67 and MT, and silver staining was conducted to localize AgNORs. The obtained results were subjected to statistical analysis using Statistica software. Results indicate that manifestation of AgNORs does not correlate with any of the studied antigens (ER, PgR, Ki-67, MT) (p>0.05). Moreover, no relationship could be demonstrated between the intensity of MT expression and proliferation markers or steroid receptor status (p>0.05). A negative correlation was shown between the expression of ER and Ki-67 (p=0.0009). The most intense proliferative activity was demonstrated in cases of breast cancer showing PgR expression but no ER expression (p=0.015), while the lowest proliferative activity was detected in breast cancers with expression of both ER and PgR (p<0.05).     

乳腺肿物Bcl—2表达与激素调节的相关研究

用免疫组化方法，观察乳腺癌及良性病变是否有Bcl－2表达；Bcl－2表达及丧失与激素受体的相关性；Bcl－2表达与肿瘤分级的关系等。结果发现Bcl－2表达与ER、PR、肿瘤组织分级显著相关，Bcl－2表达阳性的乳腺癌多伴有ER＋（75％）、PR＋（70％），而Bcl－2阴性表达与预后较差的分子标志呈正相关，即ER、PR阴性率高、组织分级高。我们的发现支持了乳腺癌Bcl-2表达受激素调节的假说。     

乳腺癌ER、PR、HER-2在原发灶及复发转移灶中表达变化

目的：探讨ER、PR及Her-2在乳腺癌原发和复发转移灶中的表达变化及其相关性。方法：免疫组化法检测45例乳腺癌原发及复发转移灶中的ER、PR及HER-2表达。结果：ER在原发灶和复发转移灶之间的变化率为66.67%（30/45）,PR总的变化率为17.78%,cerbB2癌基因蛋白总的变化率13.33%。结论：ER在乳腺癌原发灶和复发转移灶之间的表达的差异具有统计学意义（P〈0.05）。PR及cerbB2癌基因蛋白的表达在原发灶和复发转移灶之间差异无显著性（P〉0.05）。     

Expression of oestrogen and progesterone receptors in low-grade endometrial stromal sarcomas

We analysed oestrogen receptor (ER) and progesterone receptor (PR) expression in a retrospective series of 21 low-grade endometrial stromal sarcomas (LGSSs). Archival formalin-fixed and paraffin-embedded material was analysed by immunohistochemistry. ER and PR were measured with monoclonal antibodies and the peroxidase-antiperoxidase method and a score was calculated as for breast carcinoma based on both the percentage of positive tumour cell nuclei and the staining intensity. ER were seen in 15 (71%) and PR in 20 (95%) of tumours respectively. ER expression was scored as high in three (14%), moderate in four (19%), and low in eight (38%) tumours. Six (29%) tumours did not stain for ER and all of these were positive for PR. PR expression was scored as high in eight (38%), moderate in ten (47%) and weak in two (10%) LGSSs. Only one (5%) LGSS did not stain for PR (this tumour was positive for ER). ER and PR expression in LGSS is heterogeneous. This may have implications for hormone therapy in the management of these tumours. These results suggest that ER and PR should be routinely quantified in LGSSs by immunohistochemical methods.     

ER PR 单阳性表达乳腺癌患者临床病理特征和预后分析*

目的:探讨不同的ER、PR表达对原发性侵袭性乳腺癌患者预后的影响,重点研究ER+/PR- 和ER-/PR+ 单阳性表型肿瘤的临床病理特征和预后差异。方法:回顾性分析1998年10月至2004年5 月间天津医科大学附属肿瘤医院收治的1 054 例原发性侵袭性乳腺癌患者的病例资料及随访结果,比较不同的ER、PR表达乳腺癌患者的临床病理特征和预后,明确ER+/PR- 和ER-/PR+ 单阳性表型肿瘤之间存在的差异。计算生存率采用Kaplan-Meier 方法,生存率比较应用Log-rank 检验。经COX多因素分析得出独立的预后影响因素。结果:ER+/PR- 表型肿瘤易出现于年长、绝经后的女性,肿瘤直径较小,组织分化程度较高。生存分析显示:ER+/PR+ 组预后优于ER-/PR- 组（OS:P=0.000,DFS :P=0.000）,ER或PR单阳组预后介于ER+/PR+ 组和ER-/PR- 组之间。相对于ER-/PR- 表型肿瘤,ER+/PR- 的生存优势强于ER-/PR+ ,ER+/PR- 的无瘤生存优于ER-/PR+（P=0.035）,而两者之间总体生存无明显差异（P=0.890）。 不同的ER、PR阳性表达是影响乳腺癌患者内分泌治疗的无瘤生存的独立因素（P=0.023）。 结论:ER+/PR- 和ER-/PR+ 是两种临床病理特征和预后完全不同的乳腺癌,ER-/PR+ 肿瘤表现的侵袭性行为更强,应该采取更为积极的治疗措施。ER-/PR+ 表型乳腺癌可能具有独特的生物学特征。      

Luminal A型乳腺癌的激素受体表达与绝经的相关性

目的探讨Luminal A型乳腺癌的激素受体表达水平与绝经的相关性,进一步认识该类乳腺癌的生物学特性。方法回顾性分析江苏省肿瘤医院2009年1月至2012年10月收治的135例LuminalA型乳腺癌患者的雌激素受体（estrogenreceptor,ER）及孕激素受体（progesteronereceptor,PR）的表达水平（高表达（H）〉50％;低表达（L）≤50％）,比较ER、PR的不同表达分组在绝经前后患者中的差异及ER、PR间的相关性。结果绝经前LuminalA型乳腺癌ER—H／PR-H表达最常见（63．8％）;ERH／PR—L表达在绝经后患者中最常见（51．1％）,在绝经前少见（17．0％）。ER、PR的相关性在绝经前比绝经后更明显（P值：0．003VS．0．047）。结论绝经前后的LuminalA型乳腺癌患者存在ER、PR的不同表达的差异性分布,体内雌激素水平可能是引起差异的原因。