子宫内膜样腺癌中LYVE-1的表达与淋巴道转移关系

目的:观察子宫内膜样腺癌中淋巴管的分布特点及增殖状态,研究肿瘤淋巴管生成与淋巴道转移的关系。方法:收集80例子宫内膜样腺癌及其相应的正常子宫内膜组织标本,采用免疫组化双标记技术,运用淋巴管特异标记物LYVE-1检测微淋巴管密度(MLD),LYVE-1与Ki-67进行双标免疫组化染色检测淋巴管增殖活性。结果:子宫内膜样腺癌肿瘤边缘区淋巴管多呈管样扩张状,而肿瘤其他区域多为呈闭索状。子宫内膜样腺癌组织中MLD较正常子宫内膜组织显著性增高(P<0.05),MLD在肿瘤边缘区、低分化子宫内膜样腺癌组、伴淋巴结转移组中显著增高,在临床分组间无显著差异。子宫内膜样腺癌中淋巴管内皮细胞Ki-67指数较正常子宫内膜组织增高(P<0.05),肿瘤边缘区Ki-67阳性表达的微淋巴管比肿瘤其他区域、有淋巴结转移组比无淋巴结转移组有显著性增高(P<0.05)。结论:子宫内膜样腺癌组织中存在淋巴管生成,淋巴管主要分布在肿瘤边缘区且淋巴管内皮细胞增殖活性增高。淋巴管密度与子宫内膜样腺癌分化程度、淋巴道转移有关,与临床分期无明显关系。检测淋巴管密度和增殖状态对预测淋巴道转移可提供一定理论的依据。     

VEGF和CD31在子宫内膜样腺癌中的表达及其临床意义

目的:检测血管内皮生长因子(VEGF)和CD31在不同子宫内膜组织中的表达情况。方法:采用免疫组化方法检测VEGF、CD31在52例子宫内膜样腺癌组织、22例子宫内膜不典型增生组织及21例正常子宫内膜组织中的表达,对结果进行量化分析。结果:(1)VEGF在正常子宫内膜组织、不典型增生组织及子宫内膜样腺癌中表达的阳性率分别为23.8%、31.8%、65.4%;CD31在正常子宫内膜组织、不典型增生组织及子宫内膜样腺癌组织中标记的微血管密度(microvessel density,MVD)分别为23.6±11.7、31.5±17.7、51.9±21.1。VEGF的阳性表达及CD31-MVD(CD31标记的MVD)在子宫内膜样腺癌组织中明显高于不典型增生及正常子宫内膜组织(P0.05)。(2)VEGF在子宫内膜样腺癌中的表达,与淋巴结转移有关(P0.05)。CD31-MVD与肿瘤分期、浸润肌层深度、组织学类型有关(P0.05)。(3)在子宫内膜样腺癌组织,VEGF表达与CD31-MVD无明显相关性(r=0.095,P=0.504)。结论:VEGF表达、CD31-MVD在子宫内膜样腺癌组织中增高,可能促进子宫内膜样腺癌的发生发展及转移浸润。     

子宫内膜样腺癌中垂体肿瘤转化基因1表达与肿瘤侵袭转移的关系

目的探讨垂体肿瘤转化基因1(PTTG1)调控碱性成纤维细胞生长因子(bFGF)、基质金属蛋白酶-2(MMP-2)蛋白表达在子宫内膜癌发生、侵袭和转移中的作用及意义。方法采用免疫组化方法,结合组织芯片技术,检测2005年1月至2009年9月上海交通大学附属上海市第一人民医院124例子宫内膜样腺癌、28例内膜不典型增生、35例正常内膜组织中PTTG1、bFGF和MMP-2的表达水平,结合临床病理因素进行分析。结果 PTTG1、bFGF和MMP-2在子宫内膜样腺癌中的阳性表达率分别为63.7%、73.4%、50.8%,与正常内膜组和不典型增生组比较,差异有统计学意义(P<0.01)。PTTG1蛋白与手术病理分期显著相关(P<0.01),bFGF表达与肿瘤肌层浸润和淋巴结转移明显相关(P<0.05),而MMP-2蛋白表达与肿瘤淋巴结转移显著相关(P<0.01)。子宫内膜样腺癌组织中PTTG1和bFGF、MMP-2的表达均存在正相关关系(r=0.262,P=0.003;r=0.360,P<0.001)。结论 PTTG1可能上调bFGF和MMP-2蛋白的表达,在子宫内膜癌侵袭和转移中起重要作用。     

芳香化酶蛋白及性激素受体等在子宫内膜病变组织中的表达变化及意义

目的探讨芳香化酶蛋白、雌激素受体（ER）、孕激素受体（PR）及细胞增殖相关核抗原Ki67在子宫内膜病变组织中的阳性表达率及其在子宫内膜病变的诊断和治疗中的价值。方法采用免疫组化链霉菌抗生物素蛋白-过氧化物酶链接（SP）法,检测148例子宫内膜病变患者（观察组,其中子宫内膜增殖症30例,轻、中、重度子宫内膜非典型增生各10例,子宫内膜腺癌88例）及30例因患宫颈原位癌行子宫全切除术患者的正常子宫内膜组织（对照组,其中增殖期及分泌期子宫内膜各15例）中芳香化酶蛋白、ER、PR及Ki67的阳性表达率。结果（1）观察组子宫内膜增殖症、子宫内膜非典型增生组织芳香化酶蛋白、ER、PR、Ki67的阳性表达率与对照组增殖期内膜比较,差异无统计学意义（P〉0．05）;（2）观察组子宫内膜腺癌组织芳香化酶蛋白阳性表达率为64％（56／88）,与子宫内膜非典型增生（23％,7／30）、子宫内膜增殖症（13％,4／30）及对照组（0／15）比较,差异均有统计学意义（P〈0．01）;（3）芳香化酶蛋白的阳性表达率与子宫内膜腺癌的临床分期（Ⅰ期61％、Ⅱ期77％、Ⅲ期70％、Ⅳ期67％）、肿瘤细胞分化级别（高分化64％,中分化74％,低分化58％）、有无淋巴转移（转移59％,无转移67％）无明显相关性（P〉0．05）。（4）子宫内膜腺癌组织中ER、PR、Ki67的阳性表达率分别为22％（19／88）、19％（17／88）、41％（36／88）,与对照组分别比较,差异均有统计学意义（P〈0．01）。结论子宫内膜良性病变组织与正常内膜组织中,芳香化酶蛋白表达无明显差异;子宫内膜腺癌组织中芳香化酶蛋白的过度表达,可作为诊断子宫内膜腺癌的指标之一。     

缺氧诱导因子-1α、金属基质蛋白酶-2在子宫内膜癌中的表达及意义

目的探讨缺氧诱导因子-1α(H IF-1α)、金属基质蛋白酶-2(MMP-2)在子宫内膜癌中的表达及其临床意义。方法2006年8月至2009年9月在中国医科大学附属盛京医院应用免疫组化SP法检测52例子宫内膜腺癌、23例子宫内膜不典型增生、18例正常子宫内膜组织中H IF-1α及MMP-2的表达情况。结果H IF-1α、MMP-2在子宫内膜癌组织中的阳性表达率(73.08%,71.15%)明显高于正常子宫内膜组织(22.22%,16.67%)及不典型增生子宫内膜组织(39.13%,34.78%),差异有统计学意义(P<0.05)。随着子宫内膜腺癌临床分期、病理组织学分级的提高,H IF-1α及MMP-2的表达也随之增强;二者在子宫内膜癌有淋巴结转移组中的表达高于无淋巴结转移组,差异有统计学意义(P<0.05)。子宫内膜组织中H IF-1α、MMP-2蛋白的表达呈正相关(rs=0.543,P<0.01)。结论H IF-1α、MMP-2在正常子宫内膜、子宫内膜不典型增生及子宫内膜癌组织中的表达依次增高,提示H IF-1α及MMP-2在子宫内膜癌发生发展中起重要作用,可将其视为子宫内膜癌潜在侵袭性的肿瘤标志物。     

卵巢癌相关成纤维细胞与卵巢癌淋巴结转移的关系

目的:探讨肿瘤相关成纤维细胞(CAFs)与卵巢癌临床病理学特征特别是淋巴结转移的关系,研究CAFs在卵巢癌淋巴管生成和淋巴管内皮细胞(LEC)增殖迁移中的作用。方法:免疫组化法检测、计算机图像处理软件分析71例卵巢癌组织间质中α-平滑肌肌动蛋白(α-SMA)阳性面积百分比,以此代表卵巢癌CAFs的数量。用D2-40标记淋巴管内皮细胞,检测淋巴管密度(LVD)。EdU标记法和Transwell迁移实验检测与CAFs共培养前后淋巴管内皮细胞增殖和迁移情况。结果:卵巢癌有淋巴结转移组间质中CAFs百分比明显高于无淋巴结转移组(P=0.024),分别为(29.39±4.32)%和(22.56±6.78)%。卵巢癌间质CAFs数量与淋巴管密度呈正相关(r=0.504,P=0.0003)。与卵巢癌成纤维细胞共培养后,淋巴管内皮细胞增殖增多2.8倍(P<0.0001),迁移增多5.2倍(P<0.0001)。结论:卵巢癌间质成纤维细胞可能通过促进淋巴管内皮细胞增殖、迁移和淋巴管生成,参与卵巢癌的进展和淋巴结的转移。     

子宫内膜样癌组织中HGF/c-Met的表达及其与细胞增殖、血管生成的关系

目的:研究肝细胞生成因子HGF及其受体c- Met在子宫内膜样癌组织中的表达及其与肿瘤细胞增殖、血管生成的关系。方法:应用免疫组化S- P法,检测52例子宫内膜样癌、22例正常子宫内膜组织中HGF、c -Met表达,并结合肿瘤的增殖细胞指数、微血管密度,对结果进行统计学分析。结果: 1.子宫内膜样癌组织中HGF及c- Met表达较正常子宫内膜组织明显增高(P<0 .05); 2.c Met表达越强,子宫内膜样癌的期别越晚、分化越低; 3.子宫内膜样癌组织中,HGF和c -Met表达阴性、阳性、强阳性组中,PCNA指数、微血管密度依次升高,差异有显著性(P<0. 05)。结论:HGF、c- Met过度表达与子宫内膜样癌的发生发展有关;c Met可作为子宫内膜样癌的预后指标之一;HGF/c -Met可促进肿瘤细胞增殖及血管生成。     

S100A14在子宫内膜癌中的表达及其意义

目的:探讨S100A14在子宫内膜样腺癌中的表达及其临床意义。方法:采用免疫组化法检测子宫内膜癌组织、不典型增生子宫内膜组织、单纯性增生子宫内膜组织及正常子宫内膜组织中S100A14的表达情况。结果:84例子宫内膜癌患者中,高、中分化与低分化癌组织中S100A14表达具有统计学差异(P=0.020,P=0.034);行淋巴结清扫的74例子宫内膜癌患者中,淋巴结阴性与淋巴结阳性癌组织中S100A14表达有统计学差异(P=0.044)。子宫内膜癌组织中S100A14的表达与正常内膜组织比较,差异有统计学意义(P=0.034),单纯性增生、不典型增生子宫内膜组织中S100A14的表达与正常内膜组织比较,无统计学差异。结论:S100A14的表达下调与子宫内膜样腺癌的恶性程度及肿瘤转移程度相关。     

COX-2和VEGF在子宫内膜腺癌中表达及其与肌层侵袭和淋巴转移的关系

目的 探讨COX-2和VEGF在子宫内膜腺癌中表达与肌层侵袭和淋巴转移的关系.方法 收集上海交通大学附属第六人民医院2006年9月至2008年7月手术切除子宫内膜腺癌标本60例,根据有无深肌层浸润和(或)淋巴转移将子宫内膜腺癌分为两组,应用荧光定量PCR、蛋白印迹法测定腺癌组织中COX-2、VEGF的表达水平,以正常子宫内膜组织作为对照组.结果 (1)子宫内膜腺癌组织COX-2与VEGF mRNA表达呈正相关(r=0.7137,P=0.0001);(2)对照组中COX-2和VEGF mRNA表达(4.78±1.07、3.37±0.70)均高于低危组(3.84±0.91、2.55±1.02).差异有统计学意义(P<0.05);(3)低危组中COX-2和VEGF蛋白表达(0.13±0.10、0.68±0.16)均低于高危组(0.20±0.12、0.83±0.14),差异有统计学意义(P<0.05).结论子宫内膜腺癌组织中COX-2可能上调VEGF的表达水平,促进新生血管和淋巴管生成,从而促进肌层浸润和淋巴转移,为临床预防、治疗及预后判断提供参考.     

层粘连蛋白受体基因表达与子宫内膜癌的关系

目的 探讨67ku层粘连蛋白受体(67LR)基因表达与子宫内膜癌的关系。方法 应用免疫组化SABC法检测1990～2001年收治的44例子宫内膜癌、15例子宫内膜增殖症、47例正常子宫内膜组织中67LR的表达;采用荧光定量逆转录聚合酶链反应(FQ-RT-PCR)方法定量检测2000～2001年收治的24例子宫内膜癌、16例子宫内膜增殖症、29例正常子宫内膜新鲜组织67LRmRNA水平。结果 67LR在子宫内膜癌、子宫内膜增殖症的表达较正常子宫内膜均明显增高(P<0.001),但前两组的表达差异无显著性(P>0.05)。高、中分化子宫内膜腺癌67LR表达较低分化者为高(P<0.05);但高、中、低分化组病例67LR mRNA水平差异无显著性(P>0.05)。67LR mRNA水平与免疫组化蛋白表达无明显相关(P>0.05)。结论 67LR蛋白过度表达可能与子宫内膜癌的发生、发展有关。67LR mRNA水平与蛋白表达水平无相关。     

Lymphatic spread in carcinoma of the vulva

A study of 153 patients with squamous cell carcinoma of the vulva is reviewed. Regional node metastases were present in 20%, and lymphatic spread proved the single most significant prognostic factor in this disease. Recurrent carcinoma developed in 47% of cases with nodal metastases. Lymph node metastases were directly related to stage of disease, tumor differentiation, lesion size, and depth of invasion. Sixty percent of nodal disease was not suspected by clinical examination. No patient developing recurrent disease after identification of positive nodes survived the disease. Surgical staging based only upon size of lesion and presence of nodal metastases appears to offer a clearer prognostic profile than conventional clinical staging. The pattern and frequency of nodal spread suggest that in selected instances modifications of the standard surgical treatment of vulvar cancer may be appropriate.     

Does the density of lymphatic vascular space invasion affect the prognosis of stage Ib and IIA node negative carcinoma of the cervix?

Abstract. Sykes P, Allen D, Cohen C, Scurry J. & Yeo D. Does the density of lymphatic vascular space invasion affect the prognosis of stage Ib and IIA node negative carcinoma of the cervix? Int J Gynecol Cancer 2003; 13: 313–316.
Lymphatic vascular space invasion (LVSI) has been noted as a poor prognostic factor in many tumors. In some studies of carcinoma of the cervix, LVSI has been demonstrated to be independent of other prognostic factors. The aim of this study is to evaluate if, by a simple quantitative technique, the density of lymphatic invasion could be correlated with the risk of recurrence in node negative early stage carcinoma of the cervix. We analyzed the pathology and clinical course of 71 consecutive patients with stage IB and IIA carcinoma of the cervix treated primarily by radical hysterectomy and pelvic lymphadenectomy. All cases had negative nodes and adequate surgical margins. There were 67 patients suitable for evaluation. Tumour type, grade, stage and the dimensions of the tumor were recorded. The density of LVSI was categorized as absent (45%), mild (15%), moderate (33%) or severe (7%) depending on the number of lymphatic vascular spaces involved per high power field in the worst affected slide. The patients were followed for 2–8½ years with a mean follow up of 4 years and 2 months. There were 13 recurrences and 7 deaths. All recurrences occurred in less than 2 years after surgery. The risk of recurrence was 40% for patients with extensive LVSI, 32% for moderate, 30% for mild and 3% if LVSI was absent. Only the presence of LVSI was associated with an increased risk of recurrence. The density of lymphatic invasion as represented by the number of lymphatic spaces occupied on the worst histological slide offered no further clinically useful information.     

卵巢癌手术时淋巴结清扫范围、数目及转移与预后关系的研究

目的 回顾性研究卵巢癌手术时淋巴结清扫范围、数目、转移和预后的关系。方法 行全子宫双附件切除术（TAHBSO）或联合腹膜后＋髂窝淋巴结扩大清扫的卵巢癌标本，全数摘取淋巴结，比较TAHBSO和扩大清扫的淋巴结数目并判断预后。结果 本组51例共取淋巴结663枚，平均13枚／例。全子宫切除5枚／例，全卵巢切除9枚／例，腹膜后淋巴结切除8枚／例，髂窝7枚／例。FIGO分期Ⅰ、Ⅱ、Ⅲ、Ⅳ期3年生存率分别为36％、15％、6％、0。结论 淋巴结转移足卵巢癌扩散的重要途径，不论其局部浸润程度，均须扩大淋巴结切除范围；保护生育功能的手术不影响腹膜后淋巴结切除数目。     

The side of groin node metastases in unilateral vulvar carcinoma

The purpose of this study was to analyze the occurrence of ipsilateral, bilateral and contralateral inguinofemoral node metastases in unilateral vulvar carcinoma. One hundred and eighty-five women with a T1 or T2 squamous cell carcinoma who underwent radical vulvectomy with bilateral inguinofemoral lymphadenectomy were surveyed. Inguinofemoral lymph node metastases were found in 23 (22.1%) out of the 104 patients with a unilateral primary tumor. These lymph node metastases were found solely on the ipsilateral side in 21 (91.3%) out of the 23 patients. One patient presented with bilateral extranodal growth in the groins. Another patient with a history of endometrial carcinoma had a right-sided vulvar tumor with contralateral groin node metastases. Half a year later, she was diagnosed with recurrent endometrial cancer on the right pelvic side-wall. Our study endorses clinical evidence that the preferential lymph flow is to the ipsilateral groin. Established lymph node metastases may disturb the normal lymph flow with contralateral metastases as a possible consequence.     

Prognostic factors in FIGO stage IB cervical cancer without lymph node metastasis and the role of adjuvant radiotherapy after radical hysterectomy

OBJECTIVES: The aim of this study was to evaluate the clinical and pathologic prognostic variables for disease free survival, overall survival and the role of adjuvant radiotherapy in FIGO stage IB cervical carcinoma without lymph node metastasis. METHODS: A retrospective review was performed of 393 patients with lymph node negative stage IB cervical cancer treated by type 3 hysterectomy and pelvic lymphadenectomy at the Hacettepe University Hospitals between 1980 and 1997. RESULTS: The disease free survival and overall survival were 87.6 and 91.0%, respectively. In univariate analysis, tumor size, depth of invasion, vaginal involvement, lympho-vascular space involvement (LVSI) and adjuvant radiotherapy were found significant in disease free survival. Overall survival was affected by tumor size, LVSI, vaginal involvement and adjuvant radiotherapy. Tumor size, LVSI and vaginal involvement were found as independent prognostic factors for overall and disease free survival in multivariate analysis. Disease free survival, recurrence rate and site did not differ between patients underwent radical surgery and radical surgery plus radiotherapy. CONCLUSION: Tumor size, LVSI and vaginal involvement were independent prognostic factors in lymph node negative FIGO stage IB cervical cancer. Adjuvant radiotherapy in stage IB cervical cancer patients with negative nodes provides no survival advantage or better local tumoral control.     

Bilateral breast tumours in acute lymphatic leukemia

Summary We report on a patient with acute lymphatic leukemia, who developed bilateral mammary deposits.     

Predictors of lymphatic failure in endometrial cancer

OBJECTIVE: The aim of this study was to identify determinants of lymphatic failure in patients with endometrial cancer after definitive primary treatment. METHODS: We observed 142 relapses in endometrial cancer patients who had primary surgery at our institution during the decade before 1994. We defined lymphatic failure as a relapse occurring on the pelvic sidewall (PSW), para-aortic area (PAA), or other node-bearing area (i.e., groin, axilla, supraclavicular, mediastinal). Mean follow-up was 72.8 months. RESULTS: We observed 44 instances of lymphatic failure--6 on the PSW only, 16 in the PAA only, 12 concomitantly in the PAA and on the PSW, and 10 confined in other node-bearing areas. By univariate analysis, body mass index > or = 30 kg/m(2), para-aortic lymph node biopsy, cervical stromal invasion (CSI), positive adnexa, myometrial invasion >50%, primary tumor diameter >2 cm, positive peritoneal cytology, positive lymph nodes (pelvic and/or para-aortic), radiotherapy, grade 3 tumor, nonendometrioid histology, and lymph--vascular invasion (LVI) significantly (P < or = 0.05) correlated with lymphatic failure. However, on Cox regression analysis, only LVI (P < 0.01, relative risk [RR] = 4.27), nodal involvement (P = 0.02, RR = 3.43), and CSI (P = 0.049, RR = 2.26) were independent predictors of lymphatic failure. Moreover, lymph node metastases (P = 0.01, RR = 19.82) and CSI (P = 0.050, RR = 3.57) independently predicted failure on the PSW, and only lymph node involvement (P < 0.01, RR = 10.15) predicted relapse in the PAA. CONCLUSION: LVI, positive lymph nodes, and CSI were the strongest predictors of lymphatic failure in endometrial cancer (31% of patients with at least one of the above three variables had a failure at 5 years). Patients with none of the above three factors had an extremely low (<1%) risk of lymphatic failure.     

Unusual regression of severe recurrent lymphatic malformation of a face after contraception and pregnancy

We report the case of a female who had suffered from progressive lymphatic malformation in the orbito-temporal region since childhood. Many surgical interventions were performed, including radical excision and shunt drainage. Despite aggressive surgical treatment, recurrence was observed after every intervention. Eventually, the condition regressed after the patient began taking a contraceptive. Moreover, it virtually disappeared after pregnancy.     

微淋巴管计数在子宫内膜癌中的意义

目的 探讨不同病理类型子宫内膜癌中微淋巴管密度与临床病理参数的关系。方法 采用S—P免疫组化染色法检测29例雌激素依赖型（Ⅰ型）子宫内膜癌及23例非雌激素依赖型（Ⅱ型）子宫内膜癌中VEGFR-3的表达以及计数微淋巴管密度（lymphatic vessel density，LVD）。结果 Ⅰ型内膜癌的LVD（50．69±16．86）显著高于Ⅱ型内膜癌（28．52±10．83）．深肌层浸润组LVD高于浅肌层浸润组，FIGO分期Ⅲ／Ⅳ期组LVD高于FIGO分期Ⅰ／Ⅱ期组，淋巴结转移组LVD高于无淋巴转移组，子宫外转移组LVD高于无子宫外转移组，差异有显著性（P〈0．05）。LVD与Ⅰ型内膜癌的FIGO分期、病理分级、淋巴结转移和子宫外转移有相关性；LVD与Ⅱ型内膜癌的临床病理因素无相关性。结论 LVD与子宫内膜癌的发生可能有关，可作为Ⅰ型子宫内膜癌预后判断的参考指标。Ⅱ型子宫内膜癌可能在发病、发展、侵袭和转移过程中，具有不同于Ⅰ型内膜癌的生物学模式。