乳腺浸润性导管癌组织Ki-67表达及其分子分型的意义

目的:探讨Ki-67增殖抗原在乳腺浸润性导管癌组织中的表达及与临床病理特征、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)和抑癌基因p53的关系.方法:采用Elivison二步法进行免疫组化染色,检测102例单侧乳腺浸润性导管癌组织中Ki-67、ER、PR、C-erbB-2和p53的表达水平,并结合患者相关临床资料进行分析.结果:Ki-67高表达(≥14％)比例占82.4％ (84/102).不同分子亚型中,luminalA型Ki-67表达率最低,三阴性(导管)最高.Ki-67表达水平与单侧浸润性导管癌患者的淋巴结转移(x2=5.007,P=0.025)、TNM分期(u=705.000,P=0.032)和组织分级(单侧Fisher:P=0.042)有明显的相关性,与患者的年龄(t=1.996,P=0.052)、肿块大小(u=859.000,P=0.502)和侵犯脉管情况(xc2=0.762,P=0.383)无明显的相关性.Ki-67表达水平与ER(r=-0.273,P=0.005)、PR(r=-0.332,P=0.001)表达程度呈负相关;与C-erbB-2(r=0.327,P=0.001)、p53(r=0.343,P=0.000)表达程度呈正相关.结论:Ki-67表达与目前乳腺癌分子分型相关,其高表达是预后不良因素.     

C-erbB-2与Ki-67在子宫内膜癌组织中的表达及相关性研究

目的探讨子宫内膜癌组织中C-erbB-2与Ki-67的表达及临床意义。方法采用免疫组化法检测62例子宫内膜癌组织中C-erbB-2蛋白与Ki-67蛋白表达情况。结果 62例子宫内膜癌组织中C-erbB-2蛋白阳性表达率为64.52%（40/62）,C-erbB-2阳性表达随组织学病理分级的增加、手术病理分期进展及肌层浸润程度的加深,逐渐增高,但与有无淋巴结转移及组织学类型无关（P〉0.05）。Ki-67阳性表达率77.42%（48/62）,Ki-67表达随组织学病理分级的增加、手术病理分期进展、肌层浸润程度的加深及有淋巴结转移,也渐增强,但与组织学类型无关（P〉0.05）。C-erbB-2和Ki-67的表达呈正相关（γ=0.283,P〈0.01）。结论 C-erbB-2与Ki-67的蛋白表达均与子宫内膜癌的浸润、进展有关,而Ki-67高表达预示盆腔淋巴结转移,联合检测可用来判断子宫内膜癌的恶性程度,两者均阳性表达提示子宫内膜癌恶性程度较高,预后不良。     

ER、PR与C-erbB-2、Ki-67在乳腺癌中的表达及其临床意义

目的 探讨乳腺癌组织中ER、PR与C-erbB-2、Ki-67的表达及它们的相关性.方法 采用免疫组化检测,对356例乳腺癌患者ER、PR、C-erbB-2及Ki-67的表达、临床病理特征以及它们的相关性进行回顾性分析.结果 ER、PR、C-erbB-2及Ki-67的表达与淋巴结转移相关(P<0.05);乳腺癌组织分级...     

乳腺癌前不同病变中多种生物标志的变化规律及意义

目的探讨多种生物标志在乳腺癌前不同病变中的变化规律及意义。方法免疫组化法检测ER、PR、pS2、p53和c-erbB-2在正常乳腺组织、单纯性增生、不典型增生和早期癌中的表达。结果ER、PR表达与乳腺增生病情程度密切相关(r=0.446,P<0.0001;r=0.363,P<0.0001),阳性表达率在不典型增生组分别为64.4%和73.3%,显著高于正常组(分别为11.5%和15.4%)和单纯增生组(分别为22%和28%)。pS2、p53、c-erbB-2在癌前不同病变中的表达率较低。发现>2个指标的共表达在不典型增生组为68.9%,显著高于正常组(3.8%,P<0.01)和单纯增生组(14%,P<0.01)。结论ER、PR是促进乳腺增生发展和癌变的重要影响因子,临近癌变存在显著增高的多生物指标共表达。     

Selected Immuno-Histochemical Markers in Curettage Specimens and their Correlation with Final Pathologic Findings in Endometrial Cancer Patients

To assess the immuno-histochemical expression of various markers in, endometrial biopsies of patients with endometrial cancer, and to correlate their expression with the final pathologic findings. Sixty-two patients with primary endometrial cancer who underwent surgical treatment were included in this study. Immuno-histochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, bcl-2, Her-2/neu and Ki-67 were assessed in curettage specimens, and review of the final pathology report from hysterectomy specimens was carried out. The expression of these markers in curettage was correlated with the final tumor characteristics obtained on hysterectomy specimens. Both ER and PR were significantly more expressed in endometrioid type (EC) than non- endometrioid type (NEC) (P value of 0.004 and 0.012). On the contrary, P53, Her-2 and Ki-67 showed higher positivity in NEC than EC (P value of 0.005, 0.025 and 0.002). Positive expression of ER and PR was significantly associated with low grade tumors and superficial myometrial invasion, whereas positive expression of Her-2 and Ki-67 was significantly associated with higher grade lesions, and deep myometrial invasion. Moreover, a statistically significant inverse relationship was observed between the positivity of P53, Her-2 and Ki-67 and the positivity of ER, PR. We found that determination of immuno-histochemical markers in curettage specimens might be helpful in predicting the final pathologic findings in patients with endometrial cancer. This might be helpful in planning the extensivity of the surgery.     

1 267例乳腺癌临床与免疫组化指标的相关性分析

分析乳腺浸润性导管癌的临床特征及6种免疫组化指标表达的关系,探讨其临床意义。方法:采用免疫组化SP法对1 267例乳腺癌患者的术后肿瘤石蜡标本进行ER、PR、C-erbB-2、P53、Ki-67、VEGF检测,并与患者的临床特征进行相关分析。结果:乳腺癌组织中ER、PR、C-erbB-2的阳性表达率分别为61.4%、53.0%、36.6%;P53、Ki-67、VEGF的阳性表达率分别为42.0%、91.6%、74.7%。肿瘤直径≤2 cm组中,ER和PR表达率最高（66.8%和58.8%）,而C-erbB-2的表达率最低（32.9%）。在低年龄组（≤50岁）和临床I期的患者中,PR表达率均最高,为57.9%和58.5%。C-erbB-2在临床晚期（Ⅲ,Ⅳ期）表达率最高（45.9%）。P53、Ki-67的阳性表达均与ER阳性表达呈负相关。而P53、Ki-67、VEGF的阳性表达与C-erbB-2的表达均呈正相关。淋巴结阳性组中P53、Ki-67与ER及P53与C-erbB-2的相关程度均较淋巴结阴性组大。结论:乳腺浸润性导管癌组织中ER、PR、C-erbB-2与P53、Ki-67和VEGF之间有一定的相关性,联合检测有助于指导该类肿瘤的治疗。      

PCNA和pRb2/p130在子宫内膜癌中的表达及临床意义

目的：探讨增殖细胞抗原（ PCNA）和pRb2/p130在正常子宫内膜、子宫内膜增殖症、非典型子宫内膜增殖症和子宫内膜癌中的表达、相关性及与临床病理特征之间的关系。方法：免疫组织化学EnVision二步法检测PCNA和pRb2/p130在30例正常增生期子宫内膜、30例子宫内膜增殖症、40例非典型增生子宫内膜增殖症和76例子宫内膜癌中的表达。结果：PCNA在非典型子宫内膜增殖症、子宫内膜癌中的表达分别高于正常子宫内膜和子宫内膜增殖症,差异显著（ P＝0.043;P＝0.020）,pRb2/p130的表达分别低于正常子宫内膜和子宫内膜增殖症,差异显著（ P﹤0.05）;子宫内膜癌中,PCNA与肿瘤大小、分期、淋巴结转移和雌激素差异显著（P﹤0.05）,PCNA在子宫内膜癌中的表达显著高于子宫内膜增殖症（P＝0.045）,pRb2/p130与年龄、组织学分级、浸润深度、淋巴结转移和雌激素有差异（ P﹤0.05）,pRb2/p130和PCNA呈负相关（ r＝-0.331,P＝0.003）。结论：pRb2/p130和PCNA在非典型子宫内膜增殖症和子宫内膜癌中的异常表达,结合在一起可能成为评估识别具有高风险的子宫内膜癌患者的新参数。     

子宫内膜癌雌、孕激素受体和C-erbB-2检测的临床意义

目的 检测子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)及癌基因蛋白C-erbB-2表达的阳性率并探讨其与预后的关系.方法 用免疫组织化学法对32份子宫内膜癌标本进行了ER、PR及C-erbB-2的检测.结果 子宫内膜癌组织中ER、PR、C-erbB-2的阳性率分别为53.1%、50.0%、46.9%.ER、PR的阳性表达率与癌组织的细胞分化程度有关,随着子宫内膜癌组织学分级的增高,ER、PR阳性表达率逐渐降低,C-erbB-2的阳性表达率与肿瘤病理分级呈正相关,与ER、PR表达呈负相关.结论 ER、PR、C-erbB-2均反映了子宫内膜癌的生物学行为,其测定对预测预后、指导选择内分泌治疗具有重要意义.     

C-erbB-2、p53、Ki-67及VEGF在乳腺癌中的表达及相关性

目的探讨C-erbB-2、p53、Ki-67及VEGF在乳腺癌组织中的表达及其与乳腺癌临床病理特征之间的相关性。方法采用免疫组化SP法检测72例乳腺癌组织中C-erbB-2、p53、Ki-67及VEGF表达情况,并结合临床病理特征进行相关性分析。结果乳腺癌患者C-erbB-2、p53、Ki-67及VEGF阳性表达率分别为47.2%、48.6%、56.9%、65.3%。C-erbB-2、p53表达与淋巴结转移、雌激素受体、孕激素受体相关(P<0.05);Ki-67、VEGF与肿瘤直径、淋巴结转移相关(P<0.05);ER和PR呈正相关(P<0.05);C-erbB2与ER、PR呈负相关(P<0.05);p53与ER和PR呈负相关(P<0.05);p53、Ki-67、VEGF之间均呈正相关(P<0.05)。结论 C-erbB-2、p53、Ki-67及VEGF检测对判断乳腺癌预后有重要意义。     

Ki-67与乳腺癌临床病理特征及新辅助化疗疗效的相关性

目的：分析Ki-67与乳腺癌临床病理特征对新辅助化疗（neoadjuvant chemotherapy,NCT）疗效和预后的影响,探讨NCT疗效的预测因素。方法用免疫组化法检测320例局部晚期乳腺癌患者癌组织中ER、PR、HER-2及Ki-67表达状况。进行NCT 4～6个周期后手术。分析临床病理特征与病理完全缓解率（patho-logic complete response,pCR）之间的关系。临床病理参数与疗效分析用χ2检验,影响预后因素用Cox多因素回归分析。结果 Ki-67表达与ER（r=－0.174,P=0.002）和PR（r=－0.132,P=0.019）呈负相关,与HER2（r=0.140, P=0.012）和乳腺肿瘤大小（r=0.132,P=0.019）呈正相关;ER阴性组pCR率显著高于ER阳性组（26.9%vs 7.4%,χ2=22.761,P=0.000）;PR阴性组pCR率显著高于阳性组（22.7%vs 10.9%,χ2=7.950,P=0.005）;Ki-67高表达组pCR率18.0%（41/228）优于Ki-67低表达组8.6%（8/92）（χ2=4.552,P=0.033）;化疗后Ki-67表达下降组pCR率19.8%（48/243）优于未下降组1.3%（1/77）（χ2=15.356,P=0.000）;各分子亚型间化疗疗效差异显著,Luminal A型pCR率为1.4%（1/71）,Luminal B型pCR率为15.3%（25/163）,HER2过表达型pCR率为31.3%（14/45）,三阴性型pCR率为22.0%（9/41）（χ2=20.639,P=0.000）;用Kaplan-Meier法进行生存分析,Ki-67低表达组无病生存时间（DFS）和总生存时间（OS）均优于Ki-67高表达组,两者均为P=0.034。结论 Ki-67高表达患者对化疗更敏感,但预后较差。化疗前Ki-67的表达和化疗后Ki-67变化是影响DFS独立的预后因素。ER、PR、Ki-67指数及分子分型可以作为NCT疗效的预测指标,Ki-67指数与ER、PR、HER2之间存在相关性。     

Maspin和Ki67在子宫内膜癌中的表达及其相关性分析

目的:探讨在正常子宫内膜、子宫内膜增殖症(非典型)和子宫内膜癌中Maspin和Ki67的表达、相关性及与临床病理特征的关系.方法:采用免疫组织化学方法检测Maspin和Ki67在30例正常增生期子宫内膜、40例子宫内膜增殖症(非典型)和72例子宫内膜癌中的表达.结果:在子宫内膜癌中,Ki67表达分别显著高于正常子宫内膜和子宫内膜增殖症(P =0.043;P =0.020),Maspin表达分别显著高于正常子宫内膜和子宫内膜增殖症(P ＜0.05);Ki67与子宫内膜癌的组织学分级和分期有统计学差异(P＜0.05),Maspin与子宫内膜癌的组织学分级、分期和淋巴结转移有统计学差异(P＜0.05),Maspin和Ki67表达呈正相关(r=0.231,P =0.005).结论:在子宫内膜癌中,Maspin和Ki67的表达提示两者可能成为子宫内膜癌的预后因子.     

乳腺浸润性癌MRI表现与生物因子表达的相关性研究

目的 探讨乳腺浸润性癌MRI表现与生物因子雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体2(HER2)、肿瘤增殖抗原Ki-67、肿瘤抑制蛋白p53表达的相关性及临床意义.方法 回顾性分析69例乳腺浸润性癌患者的MRI表现及生物因子ER、PR、HER2、Ki-67、p53的表达情况,采用Spearman相关分析和分类回归树(CART)算法分析MRI表现与各生物因子表达的相关性.结果 HER2表达与淋巴结转移呈正相关(r=0.299,P﹤0.05),p53表达与病变表现为肿块呈负相关(r=-0.261,P﹤0.05);肿块分叶征象与Ki-67(r=0.472,P﹤0.01)、p53(r=0.25,P﹤0.05)阳性表达呈正相关.根据MRI表现分析各生物因子表达的CART决策树,分类准确度依次为:Ki-67(0.797)﹥ER(0.754)﹥PR(0.725)﹥HER2(0.478)﹥p53(0.464).结论 乳腺浸润性癌的MRI表现与生物因子ER、PR、HER2、Ki-67、p53的表达有一定的相关性,可作为乳腺癌的重要诊断指标.     

p27 kipl蛋白与雌、孕激素受体在子宫内膜组织中的表达及其意义

 目的　探讨 p2 7kipl、雌激素受体 (ER)与孕激素受体 (PR)在子宫内膜癌中的表达及意义。方法　用免疫组化法检测 6 6例子宫内膜癌、2 9例子宫内膜非典型增生病变和 31例正常子宫内膜组织中p2 7kipl蛋白及其癌组织中ER和PR的表达。结果　在癌组织中p2 7kipl的表达率为 5 3.0 % ,明显低于非典型增生病变的 75 .8%和正常子宫内膜的 87.1% ,并与其分级有关 ;ER和PR的表达与p2 7kipl相似。结论　p2 7kipl与此癌的发展和恶性程度有关 ,这对其治疗和预后有参考价值。     

Twist在子宫内膜样腺癌组织中的表达及其与雌激素受体α的关系

目的:研究扭曲蛋白（Twist）、雌激素受体α（estrogen receptor α,ERα)在子宫内膜样腺癌、不典型子宫内膜增生、正常子宫内膜组织中的表达。方法:应用免疫组化检测90例子宫内膜样腺癌、40例不典型子宫内膜增生、20例正常子宫内膜组织中Twist、ERα的表达。结果:在子宫内膜样腺癌、不典型子宫内膜增生和正常子宫内膜组织中Twist、ERα阳性率分别为56.7%、42.5%、5%和53.3%、62.5%、90%。Twist在子宫内膜样腺癌和不典型子宫内膜增生中的表达均高于正常子宫内膜组,差异有统计学意义（P<0.05）。子宫内膜样腺癌中,Twist与组织学分级、肿瘤浸润深度和淋巴结转移相关,差异有统计学意义（P<0.05）。Twist和ERα呈负相关（r=-0.279,P=0.008)。结论:Twist高表达、ERα低表达及两者的负相关关系暗示了它们在子宫内膜样腺癌发生发展中的重要作用。     

The impact of obesity and bariatric surgery on circulating and tissue biomarkers of endometrial cancer risk

Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery-induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III–IV obesity (body mass index ≥40 and ≥50 kg/m², respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months’ follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki-67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy-two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was −32.7 and −62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki-67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA-IR) and inflammation (hsCRP, IL-6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down-regulation of PI3K-AKT–mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease.     

乳腺癌组织中ER、PR、cerbB-2、Ki-67表达及其意义

目的探讨乳腺癌组织中雌激素受体（ER）、孕激素受体（PR）、cerbB-2和Ki-67基因的表达及其临床意义。方法采用S-P免疫组化方法,检测107例乳腺癌组织中ER、PR、cerbB-2、Ki-67的表达水平,并结合其患者的相关临床资料进行分析。结果乳腺癌组织中ER、PR、cerbB-2、Ki-67阳性表达率分别为56.1%、82.2%、71.0%、67.3%。ER、PR、cerbB-2、Ki-67阳性表达与乳腺癌腋窝淋巴结转移和临床分期显著相关（P〈0.05）。而与患者年龄、肿瘤大小无相关性（P〉0.05）。相关分析结果显示ER与PR表达呈正相关（P=0.000）,与Ki-67表达呈负相关（P=0.000）;PR与cerbB-2、Ki-67表达呈负相关（P=0.012、0.006）。结论 ER、PR和cerbB-2、Ki-67与乳腺癌的发生、发展有关,联合检测ER、PR、cerbB-2和Ki-67,有助于客观评估乳腺癌的生物学行为,从而指导临床治疗和预后判断。     

Clinical implications and prognostic value of five biomarkers in endometrial carcinoma

Objective

The aim was to identify the relationship between ER, PR, P53, Ki-67, PTEN, the association with clinicopathological parameters and the correlation with survival.

Methods

We studied 190 cases of primary endometrial carcinoma in which ER, PR, Ki-67, P53, PTEN antigens were investigated with the use of immunohistochemical methods. To evaluate the correlations among immunohistochemical staining and the age, menopause status, histological type, FIGO stage, grading, depth of invasion, lymph nodes involvement and serum tumor marker. Survival analysis was assessed within single and combined biomarkers types.

Results

The percentage of Ki-67 and P53 positive endometrial tumors was significantly higher in ER negative vs ER positive tumors (both P = 0.000). The same trend was evident in PR positive and negative group. The percentage of PTEN positive tumors was significantly higher in PR positive versus PR negative tumors (P = 0.021) but was no difference in different ER status. ER and PR status were significant predictors with FIGO staging, grading and recurrence. There was no clear association between PTEN positivity and clinicopathological parameters except more relevance with endometrioid histotype (P = 0.013). Positive Ki-67 or P53 was found to be strictly related to more aggressive features. There was statistically significant difference in different status of P53 and Ki-67 in survival time.

Conclusion

ER and PR positive tumors showed a statistically significant association with better clinical outcome, PR has more significant influence on prognosis. The percentage of positive Ki-67 or P53 was significantly higher in hormone-independent group versus in hormone-dependent group and combined Ki-67 and P53 may have more effect on prognosis in former group.     

p73、PTEN和Ki-67在子宫内膜样腺癌组织中的表达及意义

目的探讨p73、PTEN和Ki-67蛋白在子宫内膜癌前病变及内膜样腺癌中的表达及意义。方法用免疫组化SP法,在13例子宫内膜正常增生期、20例简单型增生过长、22例复杂型增生过长(包括11例不典型增生)及38例内膜样腺癌组织中检测p73、PTEN和Ki-67蛋白的表达情况。结果随着子宫内膜病变的恶性进展,p73和Ki-67蛋白的阳性表达率上调而PTEN下调,且p73和Ki-67表达上调呈显著正相关(P<0.01),Pearson列联系数为0.5144。p73和Ki-67蛋白表达与子宫内膜样腺癌组织分化程度有关(P<0.01),Ki-67和PTEN蛋白表达与子宫内膜样腺癌的临床分期和肌层浸润有关(P<0.05)。结论p73和Ki-67协同调控子宫内膜腺上皮细胞的生长、增殖,并促进癌变;PTEN表达下调是子宫内膜样腺癌的早发事件。联合检测p73、Ki-67和PTEN蛋白的表达可作为在子宫内膜癌早期诊断的参考指标并指导临床早期治疗。     

子宫内膜样腺癌组织中P53、P63和C-erbB2的表达及其意义

背景与目的:p53与C-erbB2是已被证实与子宫内膜样腺癌(endometrioidadenocarcinoma,EC)密切相关的抑癌基因和癌基因,而它们之间的相关性报道较少。p63在结构上与p53高度同源,被认为是p53突变时的一种抑癌基因,它的抑癌特性尚未确定,它在EC中的表达少见文献报道。本研究旨在探讨p53、p63和C-erbB-2基因在EC发生发展中的作用及其与EC临床病理特征的关系。方法:采用免疫组化SP法检测38例EC和23例子宫内膜增生过长(endometrialhyperplasia,EH)及10例正常增生期子宫内膜(benignproliferativeendometrium,BPE)中P53、P63和C-erbB2蛋白的表达情况。结果:(1)P53蛋白在EC组中的阳性率为31.6%,明显高于EH组和BPE组(P<0.05)。P53的表达与EC的手术病理分期和肌层浸润深度有关(P<0.005),而与组织学分级无关(P>0.05)。(2)P63蛋白在EC组中的阳性率为81.6%,与EH组、BPE组比较,差异均有统计学意义(P<0.005)。P63的表达与EC的组织学分级、手术病理分期和肌层浸润深度均无关(P>0.05)。(3)C-erbB2蛋白在EC组中的阳性率为23.2%,与EH组、BPE组比较,差异均无统计学意义(P>0.05)。C-erbB2的表达与EC的手术病理分期和肌层浸润深度有关(P<0.001,P<0.005),而与组织学分级无关(P>0.05)。(4)P53和P63在EC中的表达呈正相关(r=0.443,P<0     

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features简

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.