乳腺浸润性导管癌腋窝淋巴结转移的相关因素分析

目的研究乳腺浸润性导管癌腋窝淋巴结转移的相关因素,探讨利用乳腺及腋窝彩色多普勒超声结合肿瘤病理学检查分析预测乳腺浸润性导管癌的腋窝淋巴结转移情况。方法回顾性分析175例经过病理证实的乳腺浸润性导管癌患者,所有患者术前行乳腺及腋窝彩色多普勒超声检查,术后对肿瘤行病理检查。统计分析采用x2检验、Logistic回归分析及绘制ROC曲线。结果175例病例中,病理证实腋窝淋巴结转移者107例,肿瘤直径、肿瘤血流分级、腋窝淋巴结个数、淋巴结纵横比、淋巴结皮质最大厚度、淋巴结血流分型、肿瘤组织学分级、Ki67抗原和c—erbB-2阳性表达是影响腋窝淋巴结转移率的因素（P〈0．050）。最终进入模型的因素有淋巴结纵横比、肿瘤直径、淋巴结皮质最大厚度、肿瘤组织学分级Ⅱ、Ⅲ级及Ki67抗原阳性表达。ROC曲线下面积是0．964。结论淋巴结纵横比小、淋巴结皮质最大厚度I〉3mm、肿瘤直径≥2cm、肿瘤组织学分级高和Ki67抗原阳性提示较高的腋窝淋巴结转移率。     

Decreased expression of phosphorylated JNK in breast infiltrating ductal carcinoma is associated with a better overall survival

Phosphorylation/activation of c-jun NH2-terminal kinase (JNK) has an ambivalent role, pro-proliferation or antiproliferation, in human cancers, which is determined by different cell types and by its crosstalk with other kinases. So far, the role of phosphorylated JNK (p-JNK) in breast cancer is mostly undefined. In this study, we analyzed the expression of p-JNK, as well as p-ERK1/2 and p-38, in the pair of cancer and noncancer breast tissues, by using immunoblotting techniques. These results were further correlated with the clinicopathological characteristics and overall survival. Decreased p-JNK1/2 expression in cancer tissues was observed in 48.5% of breast infiltrating ductal carcinoma (IDC) cases and was correlated significantly with the increased tumor grade and the decreased age at diagnosis (p = 0.030 and 0.029). Interestingly, the Kaplan-Meier survival curve showed that the decreased p-JNK1/2 expression was associated with a better overall survival of IDC (p = 0.004). The expression of p-JNK1/2 was positively correlated with p-p38 (p = 0.002), but not p-ERK1/2. Furthermore, co-expressed p-JNK1/2 and p-p38 was associated with a poor overall survival of IDC (p = 0.007). In conclusion, our results indicate that the aberrant p-JNK1/2 expression and the co-expressed p-JNK1/2 and p-p38 in breast tissues may play a role in the carcinogenesis of breast IDC.     

乳腺导管原位癌伴微浸润发生腋窝淋巴结转移的相关因素分析

目的探讨乳腺导管原位癌伴微浸润(breast ductal carcinoma in situ withmicroinvasion,DCIS-Mi)患者发生腋窝淋巴结转移的危险因素。方法应用回顾性调查方法收集2000年1月至2008年10月可手术乳腺DCIS-Mi病例共174例,分析有无腋窝淋巴结转移患者的不同分子病理特征,并通过χ2检验、Spearman检验以及Logistic回归分析筛选腋窝淋巴结转移的危险因素。结果 174例DCIS-Mi患者中,有腋窝淋巴结转移者9例(5.17%)。DCIS-Mi病灶中,DCIS级别与腋窝淋巴结转移呈正相关(r=0.262,P=0.000),激素受体状态与腋窝淋巴结转移呈负相关(r=-0.192,P=0.011)。经Logistic回归分析各因素相互调整后,DCIS高级别(OR=37.191,P=0.005)和肿瘤直径≥4.0cm(OR=29.634,P=0.023)是DCIS-Mi病灶发生转移的高危因素。结论在DCIS-Mi患者中,DCIS级别高和肿瘤直径≥4.0cm者容易发生腋窝淋巴结转移,对此类患者进行个体化治疗是必要的。     

RhoA和Ezrin在乳腺浸润性导管癌中的表达及其临床意义

目的： 探讨RhoA和Ezrin在乳腺浸润性导管癌中的表达及其临床意义。 方法： 选用2008年1月至12月河北医科大学第四医院收治的乳腺浸润性导管癌患者术后石蜡标本86例。免疫组织化学染色检测肿瘤组织中RhoA和Ezrin的表达情况,分析其临床病理意义及两者的相关性。 结果： 86例乳腺浸润性导管癌组织中,RhoA的阳性表达率为60.47%,显著高于乳腺正常导管上皮组织的20%（P<0.05）;Ezrin的强阳性表达率为65.12%,显著高于乳腺正常导管上皮组织（P<005）。乳腺浸润性导管癌组织中RhoA的阳性表达和Ezrin的强阳性表达与患者年龄无关（P>0.05）,与腋淋巴结转移、组织学分级和TNM分期有关（均P<005）。乳腺浸润性导管癌组织中RhoA的阳性表达和Ezrin的强阳性表达呈正相关（P<001）。 结论： 乳腺浸润性导管癌高表达RhoA和Ezrin,并在导管癌的发生、发展过程中发挥作用。     

宝石能谱CT成像对乳腺浸润性导管癌的诊疗价值

目的:探讨宝石能谱CT成像（gemstone spectral imaging,GSI）在乳腺浸润性导管癌诊疗中的价值。方法:手术及病理证实的乳腺浸润性导管癌患者32例,共有病灶47个。由两位从事乳腺影像工作的副主任医师对图像进行盲评,分析乳腺浸润性导管癌病灶的影像特点及能谱特征。以软件自动生成的KeV-CT值曲线作为观察指标,分析浸润性导管癌病灶同正常腺体的差异。按病理结果将淋巴结分为转移组和非转移组;以淋巴结的KeV-CT值曲线斜率、碘基值以及淋巴结CT值与主动脉CT值的比值为评价指标,比较转移组淋巴结和非转移组淋巴结上述数值的差异。结果:GSI共检出44个病灶,病灶的最佳单能量图像KeV值在66~68KeV之间。碘/水(Iodine/Water)基物质图、水/脂（Water/Fat）基物质图对病灶范围、毛刺（40/44）、分叶（36/44）、钙化（11/44）、胸壁侵犯（7/44）有更清晰的显示。增强后病灶轻中度强化,CT值增加(20±6)HU。最佳单能量40KeV CTA能清晰显示肿瘤血管,以胸廓内动脉及胸外侧动脉为主（29/44）。浸润性导管癌病灶KeV-CT值曲线,与正常腺体差异明显。腋窝转移淋巴结同非转移淋巴结KeV-CT值曲线斜率在40~70KeV间差异明显,P<0.01（t=-5.5）,差异有统计学意义。不同KeV下转移组同非转移组HU淋巴结/HU主动脉差异无统计学意义。转移组与非转移组淋巴结碘基值平均值,差异有统计学意义,P<0.05（t=-2.1）。结论:GSI能提高小病灶及多发病灶的检出率。可以较准确地评估乳腺浸润性导管癌位置、范围、胸壁侵犯、腋窝淋巴结转移及血供情况,对乳腺浸润性导管癌的诊疗有较大的指导价值。     

The impact of axillary lymph nodes removed in staging of node-positive breast carcinoma

PURPOSE: Number of positive lymph nodes in the axilla and pathologic lymph node status (pN) have a great impact on staging according to the current American Joint Committee on Cancer staging system of breast carcinoma. Our aim was to define whether the total number of removed axillary lymph nodes influences the pN and thus the staging. METHODS AND MATERIALS: The records of 798 consecutive invasive breast cancer patients with T1-3 tumors and positive axillary lymph nodes who underwent modified radical mastectomy between 1999 and 2005 in our hospital were reviewed. The total number of removed nodes were grouped, and compared with the patient and tumor characteristics and the influence of the number of nodes removed on the staging was analyzed. RESULTS: The proportion of patients with > or =4 positive nodes (59%), and pN3 status (51%) were the highest in the group with 21-25 nodes removed. Compared with patients with 1-20 nodes removed, the proportion of patients with > or =4 positive nodes (52%), and pN3 status (46%) were significantly higher in those with more than 20 nodes removed. Although the proportion of Stage IIA and IIB decreased, the proportion of Stage IIIA and IIIC increased in patients with >20 nodes removed compared with those with 1-20 nodes removed. CONCLUSIONS: In patients with axillary node-positive breast carcinoma, staging is highly influenced by total number of removed nodes. Levels I-III axillary dissection with more than 20 axillary lymph nodes removed could lead to more effective adjuvant chemotherapy and increases substantially the proportion of patients to receive radiotherapy.     

Histopathologic examination of axillary sentinel lymph nodes in breast carcinoma patients

The axillary sentinel lymph node biopsy (SLNB) has gained increasing popularity as a novel surgical approach for staging patients with breast carcinoma and for guiding the choice of adjuvant therapy with minimal morbidity. Patients with negative SLNB represent a subset of breast carcinoma patients with definitely better prognosis, because their pN0 status is based on a very thorough examination of the sentinel lymph nodes (SLNs), with a very low risk of missing even small micrometastatic deposits, as compared with routine examination of the 20 or 30 lymph nodes obtained by the traditional axillary clearing. The histopathologic examination of the SLNs may be performed after fixation and embedding in paraffin, or intraoperatively on frozen sections. Whatever is the preferred tracing technique and surgical procedure, the histopathologic examination of each SLN must be particularly accurate, to avoid a false-negative diagnosis. Unfortunately, because of the lack of standardised guidelines or protocols for SLN examination, different institutions still adopt their own working protocols, which differ substantially in the number of sections cut and examined, in the cutting intervals (ranging from 50 to more than 250 microm), and in the more or less extensive use of immunohistochemical assays for the detection of micrometastatic disease. Herein, a very stringent protocol for the examination of the axillary SLN is reported, which is applied either to frozen SLN for the intraoperative diagnosis, and to fixed and embedded SLN as well.     

超声及钼靶X线对乳腺导管内癌与乳腺浸润性导管癌的诊断价值

目的:探讨乳腺导管内癌（ductal caicinoma in situ,DCIS）与乳腺浸润性导管癌（invasive ductal carcinoma,IDC）的超声及钼靶X线影像特征差异。方法:回顾性分析160例患者（包括62例DCIS患者及98例IDC患者）的超声及钼靶X线资料。结果:161个乳腺病灶中,有62个DCIS病灶（DCIS组）及99个IDC病灶（IDC组）。超声对IDC组病灶的检出率明显高于DCIS组,两组间的检出率有统计学意义（P＜0.05）;两组间病灶超声表现中形状、边界、边缘特征及血流信号差异有统计学意义（P＜0.05）。钼靶X线在两组病灶检出率差异有统计学意义（P＜0.05）;两组间病灶钼靶X线表现形状及边缘特征的例数差异有统计学意义（P＜0.05）。对于DCIS组,超声及钼靶X线病灶的检出率差异有统计学意义（P＜0.05）;在病灶边缘及乳腺腺体内钙化检出率这些方面,两种方法有统计学意义（P＜0.05）。结论:乳腺钼靶X线对DCIS腺体内钙化灶诊断率较高,乳腺超声对DCIS病灶检出、病灶边缘特征显示具有诊断优势。     

Localisation of COX-2 protein is different in breast ductal carcinoma and adjacent non-tumour ductal epithelium

Introduction A number of findings suggest that cyclooxygenase-2 (COX-2) is overexpressed in breast tumours. However, there is a lack of consensus in the literature regarding the pattern of expression of this protein in invasive breast ductal carcinoma and in the adjacent non-tumour ductal epithelium. This study compares the expression of COX-2 mRNA and protein in breast ductal carcinoma relative to non-tumour breast tissue. Material and methods We analysed the expression of COX-2 mRNA by quantitative PCR, and COX-2 protein by immunohistochemistry in invasive ductal carcinoma as well as in non-tumour adjacent ductal epithelium from 54 breast biopsies diagnosed as being invasive ductal carcinoma. As control, we analysed expression of COX-2 protein by immunohistochemistry in surgically-resected benign breast lesions. Results Our results show that COX-2 mRNA and protein are overexpressed in non-tumour ductal epithelium compared with invasive ductal carcinoma. However, the pattern of the protein expression is different in tumour and non-tumour tissue: COX-2 protein is expressed predominantly in the membrane of the non-tumour ductal epithelium (including in benign breast lesions) while, in invasive ductal carcinoma cells, it is localised in the cytoplasm. Conclusions The non-tumour ductal epithelium adjacent to invasive ductal carcinoma shows a higher COX-2 expression than does the invasive ductal carcinoma. However, the different localisation of the immunohistochemically-detected protein suggests a possible post-translational regulation of the protein.     

Extranodal extension of axillary metastasis of invasive breast carcinoma as a possible predictor for the total number of positive lymph nodes

INTRODUCTION: By the implementation of the sentinel node procedure in the treatment of breast carcinoma routine axillary lymph node, dissection can be abandoned in patients with a tumour-negative sentinel node. When the sentinel node is positive there are two options; an axillary dissection or radiotherapy of the axilla. In the latter case one is not informed about the total number of positive lymph nodes which can be of importance for the choice of adjuvant chemotherapy. In this paper we analyse whether it is possible to use histological parameters of a lymph-node metastasis to predict the number of tumour-cell-containing nodes. METHODS: Four hundred and ninety-eight patients treated for invasive breast cancer at our department from 1991 to 1996 were investigated to see whether extranodal extension of axillary metastases had a significant predictive value for the number of positive lymph nodes. Extranodal extension was scored as: no extranodal extension (NEE) and extranodal extension (EE); the latter was subdivided in minimal extranodal extension (MEE) or extensive extranodal extension (EEE). RESULTS: Of 498 patients, 230 patients had axillary involvement. NEE was seen in 83 (36.1%) patients and 147 (63.9%) had EE. Subdivision of this latter group revealed 77 patients with MEE (52%), 65 patients with EEE (45%) and five patients not further specified (3%). The number of positive nodes for the EE-group (6.9+/-0.5) was significant higher compared with the NEE-group (2.1+/-0.2) (P<0.001). The number of positive nodes was also significantly higher for the EEE-group compared to the MEE-group, 10.6+/-0.8 vs 4.0+/-0.4 (P<0.001). The predictive value for > or =4 positive axillary lymph nodes was 84.6% for EEE, 58.5% for EE and only 14.5% for NEE. These differences were significant (P<0.001). CONCLUSIONS: The presence of extranodal extension in axillary lymph-node metastases can be a good predictor for the expected number of positive nodes. This histological parameter could be of value to determine the kind of adjuvant chemotherapy after a positive sentinel-node biopsy with only radiotherapy of the axilla and no further axillary lymph-node dissection.     

STAT3在乳腺浸润性导管癌中表达水平与临床病理特征相关性研究

  目的  评价信号传导活化因子3（STAT3）在乳腺浸润性导管癌中表达情况及与临床病理指标的相关性。  方法  利用免疫组织化学方法检测具有完整临床病理资料的129例乳腺浸润性导管癌组织中STAT3表达情况, Chi-squire分析进行单因素相关分析, Logistic回归进行多因素相关分析, Multinomial logistic分析证实与浸润性导管癌组织中STAT3表达最为密切的因素, 线性回归定量分析STAT3与临床病理指标相关密切程度。  结果  单因素Chi-squire分析显示年龄、T分期、N分期、TNM分期、Ki-67表达、VEGF-C表达和VEGF-D表达与浸润性导管癌组织中STAT3表达相关; 多因素Logistic回归分析显示VEGF-C表达、VEGF-D表达、N分期和手术时年龄是影响STAT3在浸润性导管癌组织中表达的独立相关因素; Multinomial logistic分析证实VEGF-D具有最小的AIC和BIC值, 应视为对于STAT3表达的最密切影响因素; Spearman分析和线性回归分析发现STAT3在癌组织中表达水平与VEGF-D表达水平呈显著线性相关。  结论  STAT3在乳腺浸润性导管癌组织中表达与VEGF-D表达明显相关, 可能是促进乳腺浸润性导管癌淋巴结转移的机制之一。      

淋巴结转移10枚及以上的原发乳腺癌回顾性研究

目的：回顾性分析10枚及以上腋窝淋巴结转移原发乳腺癌各临床病理因素、辅助治疗方法与预后的关系。方法：对病理确诊且腋窝淋巴结转移10枚及以上原发乳腺癌患者186例，采用X^2检验和COX模型，分析诊断年龄、肿物大小、临床分期、术式、术前化疗状态、术后化疗状态、术后放疗状态、术后内分泌治疗状态、受体状态与预后的关系。结果：临床病理因素和辅助治疗方法与3、5年复发率和3、5年转移率差异均无统计学意义，P〉0．05。肿物大小与10年生存率、5年和10年无瘤生存率差异均有统计学意义，P〈0．05。临床分期10年无瘤生存率差异有统计学意义（P=0．030），而与5、10年生存率和5年无瘤生存率差异均无统计学意义，P〉0．05。术后辅助化疗、术后辅助放疗和术后辅助内分泌治疗5、10年无瘤生存率及5、10年生存率差异均有统计学意义，P〈0．05。诊断年龄、术式、激素受体状态和术前化疗状态与5年无瘤生存率、10年无瘤生存率及5、10年生存率差异均无统计学意义，P〉0．05。COX模型分析结果仅术后化疗状态是与预后相关的辅助治疗方法。结论：对于10枚及以上淋巴结转移原发乳腺癌其预后与临床病理因素和辅助治疗的选择相关。     

超声造影对乳腺癌腋窝淋巴结转移的诊断价值

目的探讨超声造影对诊断乳腺癌腋窝淋巴结转移的应用价值。方法对141例浸润型乳腺癌患者行乳腺病灶及腋窝淋巴结常规超声检查后,再对腋窝淋巴结进行超声造影,先用目测法观察淋巴结超声造影增强模式,再用QontraXt软件分析超声造影时间-强度曲线参数。根据超声造影灌注特点,将腋窝淋巴结分为淋巴结转移组（有转移组）和无淋巴结转移组（无转移组）,并与病理检查结果相比较。增强模式之间的对比采用x2检验,造影参数用单因素方差分析。结果淋巴结有转移组灌注模式表现为不均匀增强型或无增强,淋巴结无转移组表现为均匀型增强,两组灌注模式之间的差异有统计学意义（P=0．000）。两组造影剂到达时间、达峰时间、峰值强度之间的差异无统计学意义（P值分别为0．129、0．094、0．140）。淋巴结实质内高灌注区与低灌注区的差值（SImax-SImin）有转移组大于无转移组（P=0．000）。以SImax-SImin）值大于28为最佳临界点,鉴别的灵敏度为93．3％,特异度为80．8％。结论超声造影对鉴别乳腺癌腋窝淋巴结转移有-定的临床价值。     

Surgical treatment of carcinoma of the breast: IV. Prognosis according to extent of involvement of the axillary lymph nodes

This is a retrospective study of 462 patients who had masectomy and axillary dissection for carcinoma of the breast during 1971-1980. Actuarial analysis of relapse rates up to 5 years showed that the extent of involvement of axillary lymph nodes was the most important prognostic factor. Among patients without any axillary metastasis, those with tumor smaller than 2 cm, colloid, or other less common carcinomas had significantly better prognosis than those with other lesions. Patients younger than 45 years old had higher relapse rate. Among patients with four or more positive axillary nodes, those with tumors smaller than 9 cm or those with nine or fewer positive nodes also had lower relapse rate than those with larger tumors or more positive nodes. Adjuvant systemic chemotherapy has improved the prognosis of patients with four or more positive nodes. Our findings are discussed and compared to those reported in the literature.     

乳腺癌腋淋巴结转移超声诊断的多因素分析

目的：通过分析乳腺癌癌肿及其腋淋巴结的声像图表现,探讨癌肿及腋淋巴结声像图特征与病理学腋淋巴结转移的相关性。方法：回顾性分析应用超声检出的145例乳腺癌患者及其278枚腋淋巴结的声像图表现,采用单因素分析、多因素logistic回归及ROC曲线分析的方法,分别检验乳腺癌癌肿内血流特征及癌肿最大直径、腋淋巴结血流特征、径线比及最大皮质厚度与病理学腋淋巴结转移的相关性。结果：依据单因素分析,乳腺癌癌肿血流≥Ⅱ级者、癌肿直径较长者,对应病理学腋淋巴结转移率较高（P〈0．05）;周边型或混合型血流分布、径线比较小、皮质厚度较厚的腋淋巴结,其病理学淋巴结转移率较高（P〈0．05）。依据多因素分析,乳腺癌癌肿直径、淋巴结径线比和皮质最大厚度与病理学腋淋巴结转移明显相关。经ROC曲线分析,腋淋巴结最大皮质厚度是判定腋淋巴结转移的较佳指标。结论：依据乳腺癌癌肿及腋淋巴结超声影像学特征评价腋淋巴结转移,具有明显的临床实用价值。     

乳腺导管内癌的腋窝淋巴结转移率与术式选择

目的：从腋窝淋巴结转移率的角度，探讨对乳腺导管内癌(DCIS)的合理治疗方法。方法：我院1994年1月～2003年12月间收治的16例女性DCIS患者，中位年龄43岁(30～84岁)，中位随访时间62(6～114)个月，2例作Halsted根治术，11例作改良根治术，2例作全乳切除术，1例作象限切除 腋窝淋巴结清扫，术后8例作辅助化疗，3例作放疗，10例作内分泌治疗。结果：16例DCIS中，2例腋窝淋巴结有微转移。术后随访无复发，无死亡，只有1例术后4年骨扫描发现有髋转移。结论：治疗DCIS宜行肿块扩大切除(保乳手术)加术后放疗。