乳腺癌患者骨髓微转移细胞表型及骨髓血u-PA活性的研究

目的 通过检测乳腺癌患者骨髓微转移细胞表型，研究骨髓微环境。方法 采用免疫组化染色检测乳腺癌患者骨髓中肿瘤细胞中的生物学标志及骨髓血浆的u-PA活性。结果 72例乳腺癌患者中，30例（41.7%)存在骨髓微小转移灶。其转移率与原发灶肿块大小（x^2=6.417P=0.040），P53蛋白表达（X^2=5.930,p=0.025）相关。与原发灶肿瘤相比，肿瘤转移细胞的CyclinD1、P53、Ki-67、EGFR蛋白低表达，而p21蛋白高表达。骨髓血浆u-pa活性与肿块大小、腋淋巴结状况密切相关。结论 骨髓中播散肿瘤细胞处于低生长、低增殖的状态。     

乳腺癌非前哨淋巴结转移的相关危险因素分析

目的：探讨前哨淋巴结活检（SLNB）阳性乳腺癌患者非前哨淋巴结（NSLN）转移的危险因素。 方法：收集2009年7月—2013年10月新疆医科大学附属肿瘤医院收治的138例SLNB阳性的乳腺癌患者临床资料,采用单因素及多因素Logistic回归分析方法研究各项临床病理因素与NSLN转移的关系。 结果：单因素分析显示,原发肿瘤直径、组织学分级、前哨淋巴结转移率、前哨淋巴结转移灶最大径及脉管浸润与NSLN转移有关（均P<0.05）;多因素Logistic回归分析发现,原发肿瘤直径（OR=2.263,P=0.005）、前哨淋巴结转移率（OR=1.919,P=0.002）、前哨淋巴结转移灶最大径（OR=8.479,P=0.000）、脉管浸润（OR=4.518,P=0.029）是NSLN转移的独立危险因素。 结论：原发肿瘤直径、前哨淋巴结转移率、前哨淋巴结转移灶最大径及脉管浸润可作为预测乳腺癌NSLN转移的独立性指标。     

抑癌基因MMAC1在胆管癌中的表达及临床意义的研究

目的　探讨在胆管癌组织中MMAC1 PTEN基因和蛋白的表达情况及临床病理意义。方法　应用免疫组织化学和原位杂交技术检测 32例胆管癌组织中MMAC1 PTEN及MMAC1 PTENmRNA表达情况 ,同时结合病人的临床病理资料进行分析。结果　 32例胆管癌组织中MMAC1 PTEN蛋白的阳性表达率为 6 4% ,阳性反应分布在胞浆中。胆管癌组织中MMAC1 PTENmRNA阳性表达率73.6 % ,阳性信号位于胞浆中。MAC1 PTEN蛋白及MMAC1 PTENmRNA在胆管癌中的表达水平与患者性别、年龄、手术方式以及肿瘤部位无明显相关性 ,但与组织分化程度、有无浸润转移、术后生存时间明显相关 ,分化程度愈低 ,恶性程度高的其表达水平低、术后生存时间短。结论　胆管癌组织中存在着较高比例的MMAC1 PTEN蛋白和MMAC1 PTENmRNA阴性表达 ,说明在胆管癌的发生发展中 ,MMAC1 PTEN基因失活起着重要作用 ,两者的阳性表达均有一定的预后意义。对判断病人的预后有重要意义 ,同时为胆管癌的基因治疗提供依据     

SOX4在乳腺癌组织中的表达及临床意义

目的:探讨乳腺癌组织中SOX4的表达变化,并探讨其临床意义。方法 :采用免疫组化方法对正常乳腺组织及原发乳腺癌组织中的SOX4蛋白进行检测,分析其表达水平与乳腺癌患者临床病理特征间的关系。结果:SOX4在乳腺癌组织中的表达水平显著高于正常乳腺组织(P0.01),与乳腺癌组织ER、PR表达、淋巴结转移有相关性(P0.01、P0.05、P0.01);SOX4的表达与Her-2、EGFR表达、肿瘤组织学分级、患者年龄、肿瘤大小无关(P0.05)。结论:SOX4在乳腺癌组织中高表达,与淋巴结的转移有关,可能成为乳腺癌发生发展的预测指标之一。     

OPN在乳腺癌淋巴结转移中的作用

目的:探讨骨桥蛋白（OPN）在乳腺癌中的表达及其与腋窝淋巴结转移之间的关系。方法:采用免疫组织化学方法检测 66例乳腺癌、28例乳腺良性肿瘤、37例癌旁乳腺组织和29组腋窝转移淋巴结中OPN的表达，分析OPN表达与腋窝淋巴结转移及其他临床病理特征的关系。结果:乳腺癌组织中OPN的表达水平（4.83）明显高于癌旁乳腺组织（1.86）和乳腺良性肿瘤（2.18)（P＜0.01)；乳腺癌淋巴结转移阳性组与阴性组之间、乳腺癌原发病灶与相应的腋窝转移淋巴结之间OPN表达差异有统计学意义（P=0.048,0.03）。乳腺癌c erbB 2阳性表达组OPN表达水平（5.22）高于c erbB 2阴性组（4.00），但差异无统计学意义（P=0.056）。乳腺癌OPN表达与患者年龄、肿瘤大小、转移淋巴结数量、组织学类型、肿瘤分级以及TNM分期无关（P＞0.05），而与淋巴结转移有关（P=0.048）。结论:OPN在乳腺癌组织中高表达，且与乳腺癌腋窝淋巴结转移密切相关。     

乳腺癌中黏着斑激酶、抑癌基因PTEN编码蛋白的表达与生物学行为相关性分析

目的 研究乳腺癌组织中黏着斑激酶（FAK）和PTEN蛋白的表达与肿瘤分化、浸润转移的关系，揭示细胞信号转导系统与乳腺癌发生发展的关系，同时为乳腺癌的基因治疗提供依据。方法 应用免疫组织化学SP法检测92例乳腺癌组织和30例乳腺良性病变组织中FAK、PTEN的表达情况及其与临床病理参数的关系。结果 （1）在92例乳腺癌中FAK和PTEN的阳性表达率分别为69．6％和51．1％，与对照组比较，差异有统计学意义（P〈0．01）；（2）FAK表达与乳腺癌肿瘤大小、腋窝淋巴结转移、临床分期呈正相关（P〈0．01），PTEN表达与乳腺癌组织学分级、腋窝淋巴结转移、临床分期呈负相关（P〈0．05）；（3）乳腺癌组织FAK表达与PTEN表达呈负相关（P〈0．01）。结论 乳腺癌FAK的高表达和PTEN的缺失表达与肿瘤发生发展、浸润转移密切相关；检测这些指标，有助于判断乳腺癌的恶性程度及生物学行为。     

联合检测大肠癌组织中PTEN与CyclinD1的表达及DNA含量的临床意义

目的:探讨大肠癌组织中PTEN和CyclinD1的表达及与DNA含量联合检测的关系及意义.方法:应用免疫组织化学SP法检测58例大肠癌及14例癌旁正常大肠黏膜组织中PTEN和CyclinD1蛋白表达;应用流式细胞术检测以上组织中PTEN和CyclinD1的DNA含量;分析它们之间及与肿瘤分期、分级的关系.结果:PTEN蛋白在大肠癌组织中的表达(65.52%)显著低于癌旁正常组织(100%),CyclinD1蛋白在大肠癌组织中的表达(60.34%)显著高于癌旁正常组织(1.72%),两种蛋白在大肠癌组织中的表达呈负相关(r =-0.71);大肠癌组织的异倍体率(68.97%)显著高于癌旁正常组织(0);PTEN阳性组的DNA指数(DNA index,DI)、S期细胞比率(S-phase fraction ,SPF)均低于阴性组(P<0.05),CyclinD1阳性组的DI及SPF均高于阴性组(P<0.05);两者的表达与肿瘤病理分级、Dukes分期及淋巴结转移相关;淋巴结转移患者的异倍体率及SPF均高于无淋巴转移患者(P<0.05).结论:PTEN和CyclinD1基因的异常改变可能参与大肠黏膜细胞的恶性转化过程,两者的变化存在相关性;DNA含量的变化可能与淋巴结转移有关.联合检测PTEN、CyclinD1蛋白及DNA含量可作为评估大肠癌病理生物学行为和预后的重要指标.     

乳腺癌前哨淋巴结中hMAM mRNA的检测及其临床意义

目的：探讨乳腺癌前哨淋巴结中人乳腺球蛋白（hMAM）基因的表达水平及其作用和意义。 方法：采用RT-PCR的方法,检测hMAM基因在65例乳腺癌患者前哨淋巴结中的表达。 结果：RT-PCR方法检测乳腺癌前哨淋巴结微转移的阳性率为79.59%,常规病理学方法检测乳腺癌前哨淋巴结转移率为65.31%,两者差异有统计学意义（P<0.05）。 结论：与常规病理学方法相比,RT-PCR方法可以明显提高乳腺癌前哨淋巴结微转移的检出率,具有重要的临床价值。     

EGFR和MMP-9在乳腺癌组织中的表达及临床意义

目的:监测乳腺癌组织中表皮生长因子受体(epidermal growth factor,EGFR)和基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)蛋白的表达,探讨其与乳腺癌的临床及病理因素之间的相关性.方法:用免疫组织化学法检测乳腺癌标本EGFR和MMP-9的表达情况,分析与乳腺癌临床分期、肿瘤大小、年龄、局部淋巴结转移和预后的关系.结果:EGFR和MMP-9在乳腺癌组织中的阳性表达率分别为41.9%和64.5%.EGFR表达与乳腺癌临床分期、肿瘤大小、淋巴结转移数目和5年生存率相关(P<0.05),与患者的年龄无关(P>0.05);MMP-9表达与乳腺癌临床分期、淋巴结转移数目和5年生存率相关(P<0.01),与患者的年龄和肿瘤大小无关(P>0.05).结论:EGFR和MMP-9能作为判断乳腺癌预后及指导临床治疗的指标.     

乳腺癌中血管内皮生长因子和抑癌基因p33ING1的表达及意义

目的观察血管内皮生长因子(VEGF)和抑癌基因p33ING1蛋白在乳腺癌组织中的表达及意义。方法采用免疫组织化学法检测90例乳腺癌组织和癌周正常组织中VEGF和p33ING1的表达水平。结果VEGF在正常乳腺组织中表达率为44.4%,在乳腺癌组织中的表达率为91.1%,两者差异有统计学意义(P<0.01),p33ING1在正常乳腺组织中表达率为94.4%,在乳腺癌组织中的表达率为63.3%,两者差异有统计学意义(P<0.01)。VEGF蛋白表达水平与乳腺癌TNM分期、淋巴结转移有关(P<0.01),p33ING1蛋白表达水平与乳腺癌肿瘤大小、TNM分期、淋巴结转移有关(P<0.05)。结论VEGF与p33ING1的表达与乳腺癌发展有关,进行VEGF与p33ING1免疫组织化学法检测对判断乳腺癌生物学行为和预后具有参考价值。     

Sentinel Lymph Node Evaluation Does Not Improve Staging Accuracy in Colon Cancer

BACKGROUND: Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel lymph node (SLN) evaluation for assessing lymph node status in colorectal cancer remains controversial. Here we evaluated the sensitivity, predictive value, and accuracy of SLN evaluation for determining lymph node status in resectable colon cancer. METHODS: A prospective phase 2 cohort study of SLN evaluation in colon cancer was conducted from September 1998 to April 2006. Patients underwent resection and SLN mapping with 1% isosulfan blue and (m99)Tc sulfur colloid injection. SLNs were evaluated by hematoxylin and eosin (HE) staining and, if findings were negative, by additional thin HE sections and immunohistochemical (IHC) staining for pancytokeratin and MOC31. Overall survival for patients with IHC-positive disease was evaluated by Kaplan-Meier analysis and the log rank test. RESULTS: SLNs were identified in 119 (99%) of the 120 patients eligible for the study. Median number of SLNs identified was 4 (range, 0-13). Forty-nine patients (40%) had nodal metastases on HE. The SLN accurately identified nodal metastases in 29 (59%) of these 49 patients and was negative for metastases in 22 patients (41%). SLNs in eight patients (7%) were negative by HE but positive by IHC staining. Positive IHC status did not affect survival after a median follow-up of 33 months (P = .41). CONCLUSIONS: The low sensitivity and high false-negative rate of SLN evaluation does not support this technique for improving the accuracy of nodal staging for patients with colon cancer. The significance of IHC-positive SLNs remains uncertain.     

Identification and evaluation of axillary sentinel lymph nodes in patients with breast carcinoma treated with neoadjuvant chemotherapy

Sentinel lymph node (SLN) biopsy has been shown to predict axillary metastases accurately in early stage breast cancer. Some patients with locally advanced breast cancer receive preoperative (neoadjuvant) chemotherapy, which may alter lymphatic drainage and lymph node structure. In this study, we examined the feasibility and accuracy of SLN mapping in these patients and whether serial sectioning and keratin immunohistochemical (IHC) staining would improve the identification of metastases in lymph nodes with chemotherapy-induced changes. Thirty-eight patients with stage II or III breast cancer treated with neoadjuvant chemotherapy were included. In all patients, SLN biopsy was attempted, and immediately afterward, axillary lymph node dissection was performed. If the result of the SLN biopsy was negative on initial hematoxylin and eosin-stained sections, all axillary nodes were examined with three additional hematoxylin and eosin sections and one keratin IHC stain. SLNs were identified in 31 (82%) of 38 patients. The SLN accurately predicted axillary status in 28 (90%) of 31 patients (three false negatives). On examination of the original hematoxylin and eosin-stained sections, 20 patients were found to have tumor-free SLNs. With the additional sections, 4 (20%) of these 20 patients were found to have occult lymph node metastases. These metastatic foci were seen on the hematoxylin and eosin staining and keratin IHC staining. Our findings indicate that lymph node mapping in patients with breast cancer treated with neoadjuvant chemotherapy can identify the SLN, and SLN biopsy in this group accurately predicts axillary nodal status in most patients. Furthermore, serial sectioning and IHC staining aid in the identification of occult micrometastases in lymph nodes with chemotherapy-induced changes.     

The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer.

BACKGROUND: Controversy exists regarding the routine use of cytokeratin immunohistochemistry (IHC) in the histopathologic examination of breast cancer sentinel lymph nodes (SLN) because the clinical significance of micrometastases detected by IHC is unclear. This analysis was performed to determine the frequency of IHC-detected micrometastases. METHODS: All patients underwent SLN biopsy, followed by completion axillary dissection. This analysis included patients who had SLN evaluated by IHC. SLN were examined by hematoxylin and eosin (H&E) stain at 2-mm intervals, with IHC in 2 sections. The axillary dissection specimen was evaluated by routine H&E staining. RESULTS: IHC was performed in SLNs from 973 patients. Of the 869 patients with negative nodes by H&E, 58 (6.7%) were "upstaged" by IHC. In 6 of 58 patients (10.3%) who had IHC-only positive SLN, nodal metastases were found in the axillary dissection specimen. CONCLUSIONS: IHC resulted in upstaging of 6.7% of patients who had negative SLN on H&E staining. These patients had a 10.3% risk of residual axillary nodal metastases. However, the clinical significance of IHC-only positive SLN requires further study.     

Optimierung des Staging beim Kolonkarzinom durch Sentinel-Lymphknoten-Biopsie

Routine determination of the nodal status in colon cancer is strongly dependent on the individual quality and technique of histopathological assessment and surgical lymph node dissection. We evaluated whether sentinel lymph node biopsy (SLNB) could contribute to an improvement in staging. At least one SLN (median n=2) was detected (detection rate 84%) in each of 38 of 45 patients with primary colon cancer. Ten of these 38 were found to have lymph node metastases by HE staining (26%), six of them in the SLN. Nine of the 28 patients that were initially nodal-negative by HE revealed one micrometastasis and eight cases of isolated tumor cells by immunohistochemical (IHC) staining (32% upstaging response). Including the IHC-positive cases, 19 of the 38 patients were nodal-positive (50%), 15 of them with tumor-infiltrated SLN (overall sensitivity of SLNB 79%). Using the dye method, SLNB is clinically practicable and leads in the majority of the patients to the detection of SLN. The selective, intensified histopathological assessment of SLN identifies small tumor cell deposits in a relevant percentage of patients with little and clinically practicable effort.     

The association of cytokeratin-only-positive sentinel lymph nodes and subsequent metastases in breast cancer

INTRODUCTION: The purpose of this study was to better characterize the clinical significance of cytokeratin immunohistochemistry (IHC)-only-positive lymph node metastases among patients with breast cancer. METHODS: We performed a retrospective review of 334 patients who underwent sentinel lymph node (SLN) biopsy from 1 February 1997 through 31 July 2001. SLN biopsies were evaluated using standard hematoxylin and eosin (H&E) techniques. If H&E was negative, cytokeratin IHC was performed. We then evaluated the incidence of subsequent regional and distant metastatic disease. RESULTS: Cytokeratin IHC was performed on 183 sentinel node biopsies from 180 patients comprising a total of 427 sentinel lymph nodes. The procedures included lumpectomy and SLN biopsy (n = 83), mastectomy with SLN biopsy (n = 7), lumpectomy with SLN biopsy and completion axillary dissection (n = 80), and modified radical mastectomy with SLN biopsy and completion axillary dissection (n = 13). Cytokeratin IHC was negative in 175 axillary specimens and positive in 8 (4.4%) from 8 different patients. In these eight specimens, deeper sections with subsequent H&E staining additionally identified micrometastasis in four patients. Three of these 8 patients (37.5%) developed distant metastatic disease compared with 1 of the 172 patients (0.6%) with negative cytokeratin IHC (P < .001). Additionally, one of the cytokeratin-positive patients developed regional nodal metastasis compared with none of the 172 cytokeratin-negative patients. CONCLUSIONS: Cytokeratin IHC provides a clinically relevant adjunct to H&E staining for evaluating sentinel lymph nodes in breast cancer. These data suggest that patients with cytokeratin-positive sentinel nodes are at increased risk for development of regional and distant metastatic disease.     

乳腺癌患者腋窝前哨淋巴结微转移及孤立癌细胞的评价

目的 评价连续切片及免疫组化技术在乳腺癌前哨淋巴结(SLN)转移诊断中的价值,探讨微转移和孤立癌细胞的临床意义.方法 对80例腋窝淋巴结阴性的乳腺癌患者,用99mTc-SC和异硫蓝联合法进行前哨淋巴结活检(SLNB),对所有SLN和非SLN进行常规HE染色及免疫组织化学分析.结果 78例(97.5%)成功检出SLN,其中76.5%的SLN同位素和染料检查均为阳性.32例(41%)SLN转移阳性,其中13例(40.6%)为微转移.共有14例(43.8%)患者SLN是惟一阳性的淋巴结.SLN预测腋窝状态的敏感性、特异性和准确性分别为96.9%,100%和98.7%.SLN转移的患者,其SLN之外的转移率明显高于仅有微转移的患者(78.9%vs.23.1%).结论 连续切片及免疫组化技术是乳腺癌SLN转移诊断的敏感方法.仅有SLN微转移患者的SLN之外的腋窝淋巴结转移率低,但其预后意义及对手术方案的影响尚待进一步研究.     

乳腺癌患者皮肤微转移灶的临床意义

目的 探讨检测乳腺癌患者皮肤微转移灶的临床意义。方法 从皮肤距肿瘤最近点及乳头乳晕复合体正中切面取材，分别进行常规病理及细胞角蛋白单抗免疫组织化学法（immunohistochemistry，IHC）检测60例乳腺癌患者标本。结果60例乳腺癌中，常规病理检测出有乳头乳晕复合体浸润的3例（占5，0％），IHC检测出7例（占11．7％），两者间有统计学意义（X^2=2.25，P〈0．05）；常规病理检查及IHC法均检测出4例有皮肤浸润（占6．7％），其中3例两种方法均证实皮肤和乳头乳晕复合体同时有癌浸润。结论 IHC对乳头乳晕复合体的微转移灶的检出率高于常规病理，皮肤及乳头的受累率较低，如无受累，可行保留皮肤的乳房切除术。     

Does the Method of Biopsy Affect the Incidence of Sentinel Lymph Node Metastases?

More detailed examination of the sentinel lymph node (SLN) in breast cancer has raised concerns about the clinical significance of micrometastases, specifically isolated tumor cells detected only through immunohistochemical (IHC) staining. It has been suggested that these cells do not carry the same biologic implications as true metastatic foci and may represent artifact. A retrospective institutional review board-approved review was conducted on clinically node-negative breast cancer patients who underwent SLN biopsy (SLNB) between 1997 and 2003. Retrospective analysis of tumor characteristics and the method of the initial diagnostic biopsy were correlated with the presence and nature of metastatic disease in the SLN. Of 537 SLNBs, 123 (23%) were hematoxylin-eosin (H&E) positive. SLN positivity strongly correlated with tumor size (p<0.001) and tumor grade (p=0.025), but not with the method of biopsy (needle versus excisional biopsy). Prior to July 2002, we routinely evaluated H&E-negative SLNs with IHC (n=381). Of the 291 H&E-negative patients, 26 had IHC-only detected micrometastases (9%). The likelihood of detecting IHC-only metastases did not correlate with tumor size or grade, but was significantly higher in patients undergoing excisional biopsy than core needle biopsy. While the method of biopsy has no demonstrable effect on the likelihood of finding metastases in the SLN by routine serial sectioning and H&E staining, it may significantly impact the likelihood of finding micrometastases by IHC. IHC should not be used routinely in the evaluation of the SLN and caution should be used when basing treatment decisions (completion axillary lymph node dissection or adjuvant therapy) on IHC-only detected micrometastases.     

Use of sentinel node mapping for cancer of the colon: 'to map or not to map"

Sentinel lymph node (SLN) mapping has become a cornerstone of oncologic surgery because it is a proven method for identifying nodal disease in melanoma and breast cancer. In addition, it can ameliorate the surgical morbidity secondary to lymphadenectomy. However, experience with SLN mapping for carcinoma of the colon and other visceral malignancies is limited. This study represents an update to our initial pilot experience with SLN mapping for carcinoma of the colon. Consenting patients over the age of 18 diagnosed with adenocarcinoma of the colon were included in this study. At the time of operation, 1 to 2 mL of isosulfan blue was injected with a 25-gauge needle into the subserosa at 4 sites around the edge of the palpable tumor. The SLN was identified visually and excised followed by a standard lymphadenectomy and surgical resection. SLNs were evaluated by standard hematoxylin and eosin (H&E) evaluation as well as immunohistochemical (IHC) techniques for carcinoembryonic antigen and cytokeratin if the H&E was negative. Sixty-nine patients underwent SLN mapping. A SLN was identified in 93 per cent (64 of 69) of patients. Nodal metastases were identified in 38 per cent (26 of 69) of patients overall. In 5 patients, the only positive node identified was the SLN, 2 of which were positive by IHC criteria alone. Therefore, 3 per cent (2 of 69) of patients were upstaged by SLN mapping. This technique was 100 per cent specific while being 46 per cent sensitive. Fourteen patients had false-negative SLNs. Metastasis to regional lymph nodes remains the key prognostic factor for colon cancer. SLN mapping is feasible for colon cancer and can identify a subset of patients who could benefit from adjuvant chemotherapy. Although SLN mapping did not alter the surgical management of colon cancer, it does make possible a more focused and cost-effective pathologic evaluation of nodal disease. We do not suggest routine utilization of SLN mapping for colon cancer, but we believe that the data supports proceeding with a national trial.