鳞癌相关抗原在鳞癌及相关良性疾病中的临床意义

探讨鳞状细胞癌相关抗原（squamous cell carcinoma-related antigen,SCC-Ag）在鳞状细胞癌（鳞癌）和良性疾病中的诊断和临床监测意义及其与病理分级、临床分期的关系。采用微粒子酶免疫分析技术对167例鳞癌患者、96例相关良性疾病患者和96名健康对照者进行了血清SCC-Ag水平的检测,对各组SCC-Ag的表达水平和阳性率进行统计学分析。结果表明,鳞癌患者血清SCC-Ag表达水平显著高于健康对照者和良性疾病患者（P〈0.01）,SCC-Ag对鳞癌的诊断灵敏度为61.1%、特异性为91.7%,其ROC曲线下面积为0.825,表示SCC-Ag对鳞癌的诊断较为准确,可作为重要的诊断依据;宫颈鳞癌SCC-Ag表达水平和阳性率与临床分期呈正相关,但与病理分化不相关;良性疾病患者和健康对照组的SCC-Ag表达水平分布差异显著（P〈0.05）。血清SCC-Ag表达水平可作为肺鳞癌、宫颈鳞癌以及食管鳞癌诊断的特异性指标,在鳞癌及良性疾病的鉴别诊断中有很大的临床意义。     

CD138 在宫颈病变组织中的表达及临床病理学意义

目的:研究CD138在宫颈正常黏膜组织、上皮内瘤变(CINⅠ/Ⅱ和CINⅢ)和宫颈鳞癌组织中的表达,探讨CD138在宫颈鳞癌淋巴结转移、CD68表达、微血管密度和临床分期中的临床病理学意义。方法:采用免疫组织化学方法检测CD138在120例宫颈鳞癌、106例CINⅢ、14例CINⅠ/Ⅱ、54例正常子宫黏膜组织中的表达情况。结果:CD138表达在宫颈癌组织最低,其次是正常宫颈黏膜组织、CINⅠ/Ⅱ和CINⅢ最高,其差异具有显著性意义(P0.001)。CD138表达率在未发生淋巴结转移的宫颈癌组高于淋巴结转移组(P0.05)。在宫颈癌早期(0期和Ⅰ期)CD138的表达率最高,在Ⅱ期表达率最低(P0.001)。CD138表达率在宫颈癌组织中CD68呈阳性组明显低于阴性组(P0.05)。宫颈癌微血管密度在CD138表达呈阳性组明显低于阴性组(P0.05)。结论:CD138是宫颈鳞癌发生发展过程的抑制因素之一,尤其在淋巴结转移中作用明显,因此可作为判定宫颈鳞癌进程的参考指标。     

血清TSGF水平与宫颈癌患者术前淋巴结转移的相关性

目的:探讨血清肿瘤特异性生长因子(Tumor specific growth factor,TSGF)水平与宫颈癌患者术前淋巴结转移的相关性.方法:选取2019年1月至2020年10月郾城区中医院收治的102例进行腹腔镜下广泛性子宫切除术的宫颈癌患者作为研究对象.检测患者术前血清肿瘤特异性生长因子(TSGF)、糖类抗原125(Carbohydrate antigen,CA125)和鳞状上皮细胞癌抗原A(Squamous cell carcinoma antigen,SCCA)水平,并通过淋巴结清扫术判断患者的淋巴结转移情况,比较淋巴结转移与未转移患者的一般资料、TSGF、CA125和SCCA水平;并对患者淋巴结转移情况与三种血清标志物的水平进行相关性分析,绘制ROC曲线图.结果:共有47例(46.08％)宫颈癌患者发生淋巴结转移,55例(53.92％)未发生淋巴结转移;转移组TSGF、CA125、SCCA水平明显高于未转移组(P<0.05);经Logistics回归分析结果显示,TSGF、CA125、SCCA高表达与宫颈癌患者术前淋巴结转移有关(OR>1,P<0.05);ROC曲线显示,血清TSGF、CA125、SCCA水平预测宫颈癌患者术前淋巴结转移的AUC>0.7.结论:血清TSGF、CA125、SCCA水平与宫颈癌患者术前淋巴结转移有关,且TSGF、CA125、SCCA在预测淋巴结转移中具有较高价值.     

血清鳞状细胞癌相关抗原联合IL-6、TGF-β在宫颈癌中的诊断价值及临床意义

目的 探讨鳞状细胞癌抗原(SCC-Ag)联合白介素-6(IL-6)、转化生长因子-β(TGF-β)在宫颈癌诊断中的价值,并分析其临床意义.方法 选取宫颈癌组患者68例,宫颈上皮内瘤变(CIN)组患者48例,对照组36例,分别采用ELISA检测血清IL-6、TGF-β和ECLIA检测SCC-Ag.比较三组患者SCC-Ag、IL-6、TGF-β变化,并采用Pearson相关分析法进行相关性分析.结果 与对照组比较,宫颈癌组SCC-Ag升高;CIN组和宫颈癌组IL-6降低,TGF-β升高,差异具有统计学意义(P＜0.05).与CIN组比较,宫颈癌组SCC-Ag和TGF-β升高,IL-6降低,差异具有统计学意义(P＜0.05).与TMN分期I期比较,Ⅱ期和Ⅲ期SCC-Ag和TGF-β升高,IL-6降低,差异具有统计学意义(P＜0.05).与Ⅱ期比较,Ⅲ期SCC-Ag和TGF-β升高,IL-6降低,差异具有统计学意义(P＜0.05).Pearson相关分析结果显示,SCC-Ag与IL-6呈明显负相关(r=-0.478,P＜0.05),SCC-Ag与TGF-β呈明显正相关(r=0.592,P＜0.05),IL-6与TGF-β呈明显负相关(r=-0.526,P＜0.05).结论 血清SCC-Ag联合IL-6、TGF-β在宫颈癌早期诊断中具有重要的临床参考价值,对宫颈癌辅助诊断和疗效评估具有重要的临床意义.     

YAP1和HIF-1α表达对宫颈鳞癌患者预后的评估价值

目的 分析宫颈鳞癌患者肿瘤组织中Yes相关蛋白1(YAP1)和缺氧诱导因子-1α(HIF-1α)的表达情况及其对患者预后的评估价值。方法 收集85例宫颈鳞癌患者的宫颈癌组织(宫颈癌组)及85例子宫肌瘤患者的正常宫颈组织(对照组),采用免疫组织化学法检测YAP1和HIF-1α的表达情况。分析患者年龄、肿瘤直径、分化程度、TNM分期、浸润深度、淋巴结转移等临床特征与YAP1、HIF-1α表达的关系,并分析两种蛋白表达水平与患者总生存期(OS)和无进展生存期(PFS)的关系。结果 宫颈癌组YAP1和HIF-1α阳性表达率分别为81.18%和84.71%,YAP1和HIF-1α高表达率分别为49.41%和54.12%,对照组中YAP1和HIF-1α几乎不表达或低表达,宫颈癌组YAP1和HIF-1α阳性表达率和高表达率均显著高于对照组(P <0.05)。宫颈鳞癌组织中YAP1表达水平与肿瘤分化程度、TNM分期、浸润深度有关(P <0.05),HIF-1α表达水平与TNM分期、浸润深度和淋巴结转移有关(P <0.05)。Log-Rank检验显示,YAP1和HIF-1α低表达的患者...     

宫颈鳞癌组织中KAI1表达变化与宫颈癌复发及预后的相关性研究

目的:检测宫颈鳞癌肿瘤抑制基因1(KAI1)蛋白和mRNA的表达,结合临床病理资料探讨其与宫颈癌侵袭转移及复发和预后的关系。方法:样本包括正常对照宫颈组织20例,宫颈上皮内瘤变(CIN)组织20例,宫颈癌组织40例。采用免疫组织化学法检测3组间石蜡切片KAI1蛋白表达,采用反转录-多聚酶链反应(RT-PCR)方法检测对照组与宫颈癌组新鲜组织KAI1mRNA的表达。统计相关临床资料并随访其复发及预后情况,采用Cox比例风险模型及Logistic回归分析其与复发与预后的关系。结果:KAI1在正常宫颈组织、CIN及宫颈癌中基因及蛋白表达阳性率均呈进行性下降,组间比较差异显著(P0.01)。KAI1基因及蛋白表达均与宫颈鳞癌组织分化程度及淋巴转移有关,高分化组较低分化组阳性表达率显著降低(P0.01),未转移组中的阳性率显著高于淋巴转移组(P0.05)。宫颈癌按临床分期不同期别越早蛋白表达率越高(P0.05),基因表达率与临床期别无关。生存分析及Logistic回归分析显示组织学类型差,临床分期晚,有淋巴结转移及KAI1蛋白与RNA表达阳性患者具有高复发风险。临床分期、淋巴结转移及KAI1蛋白与RNA表达与否均为预后相关因素。结论:KAI1基因及蛋白表达强度与宫颈癌组织分化、临床分期及转移均有关,基因表达基本与蛋白表达同步变化,提示KAI1变化可能参与了宫颈癌发生发展,并且是宫颈癌复发与预后的相关因素。     

Tim-3 及其配体Galectin-9 在宫颈癌患者中的表达及意义

目的:通过检测宫颈癌、CIN与正常宫颈组织中Tim-3及其配体Galectin-9的表达水平,探讨Tim-3和Galectin-9与宫颈癌的关系。方法:用实时定量荧光PCR(qRT-PCR)和免疫组织化学法检测52例宫颈癌、30例宫颈上皮内瘤变患者和25例正常宫颈组织中Tim-3和Galectin-9的表达,并结合临床病理学资料对实验数据进行统计学分析。结果:①qPT-PCR检测Tim-3和Galectin-9的表达显示,其mRNA水平宫颈癌组高于CIN组和正常组(P0.05),CIN组高于正常组(P0.05)。②Tim-3和Galectin-9 mRNA水平与FIGO分期(P0.05)、分化程度(P0.05)和有无淋巴结转移(P0.05)均明显相关。③免疫组化结果显示宫颈癌组织中Tim-3和Galectin-9在癌巢中呈阳性表达,其MOD值明显高于CIN组织及正常宫颈组织,差异有统计学意义(P0.01)。④宫颈癌组织中Tim-3和Galectin-9的MOD值与FIGO分期(P0.05)、病理分型(P0.05)、分化程度(P0.05)和有无淋巴结转移(P0.05)均明显相关。结论:Tim-3和Galectin-9的mRNA水平和MOD值在宫颈癌中升高,并与宫颈癌的FIGO分期、分化程度和有无淋巴结转移密切相关。     

SCC-Ag、CA19-9、CEA在肺癌患者血清中的变化及临床意义

目的:探讨肺癌患者血清鳞状上皮细胞癌抗原(squamous cell carcinoma antigen,SCC-Ag)、糖类抗原CA19-9、癌胚抗原(CEA)的变化及临床意义.方法:采用微粒子酶免分析测定98例肺癌、50例良性肺病患者血清SCC-Ag水平,并用化学发光法测定其CA19-9和CEA水平,分析SCC-Ag、CA19-9和CEA检测值与肺癌临床病理特征之间的关系.结果:肺癌患者组SCC-Ag、CA19-9和CEA水平明显高于健康对照组和良性肺病组(P＜0.01),肺癌患者组SCC-Ag、CA19-9和CEA升高与肿瘤病理学类型相关和临床分期呈正相关(P＜0.01),SCC-Ag检测阳性率以鳞癌最高,CA19-9和CEA检测阳性率以腺癌最高.结论:该三项肿瘤标志物可用于肺癌的辅助诊断以及对病期和预后的判断.     

宫颈癌临床病理特征与宫旁侵犯及盆腔淋巴结转移的关系研究

目的探讨宫颈癌临床病理特征与宫旁侵犯及盆腔淋巴结转移的关系。方法选择我院2016年2月至2018年2月收治的90例宫颈癌患者为研究对象,统计分析其临床分期、生长类型、分化程度、宫旁侵犯及盆腔淋巴结转移情况,对盆腔淋巴结转移的相关因素进行Logistic多因素分析,探讨宫颈癌临床病理特征与宫旁侵犯及盆腔淋巴结转移的关系。结果 25例宫颈癌患者发生宫旁侵犯,其中内生型发生率显著高于其他生长类型,差异有统计学意义(P 0. 05);在病理类型上,鳞癌与腺癌宫旁侵犯发生率比较,差异无统计学意义(P 0. 05),但均高于腺鳞癌、小神经内分泌癌,差异具有统计学意义(P 0. 05); 10例宫颈癌患者发生盆腔淋巴结转移,与未转移患者比较,二者在高危HPV、临床分期、病理类型、肿瘤直径、宫旁侵犯、生长类型上差异有统计学意义(P 0. 05);经带入Logistic回归方程计算后发现,上述因素均是宫颈癌患者发生盆腔淋巴结转移的影响因素。结论ⅠB1期及以下病理分期的宫颈癌患者宫旁侵犯和淋巴结转移发生率并不高,内生型宫颈癌患者宫旁侵犯风险较高,高危HPV、临床分期、病理类型、肿瘤大小、宫旁侵犯、生长类型与盆腔淋巴结转移有关。     

血管内皮生长因子C在维吾尔族妇女宫颈病变组织及血清中表达的临床研究

目的 检测血管内皮生长因子C(VEGF-C)在新疆维吾尔族妇女宫颈病变中组织表达及血清含量,评价组织及血清中VEGF-C的相关性及临床意义.方法 ①应用免疫组织化学方法检测22例慢性宫颈炎、24例宫颈上皮内瘤变( CIN)及43例宫颈鳞癌组织中VEGF-C的表达.②用酶联免疫吸附实验(ELISA)方法检测15例慢性宫颈炎、23例CIN及40例宫颈鳞癌患者血清中VEGF-C的含量.结果 ①慢性宫颈炎、CIN及宫颈癌组织中VEGF-C阳性表达率分别为9.10％、87.50％、100％,差异有统计学意义(P＜0.05).②慢性宫颈炎、CIN和宫颈癌患者血清中VEGF -C含量呈逐渐增高趋势,差异有统计学意义(P＜0.05).③慢性宫颈炎、CIN和宫颈鳞癌患者组织及血清中VEGF-C的表达及含量,两者之间有相关性,差异有统计学意义(r=0.27,F=5.327,P＜0.05),组织表达越强,血清含量越高.结论 VEGF-C在新疆维吾尔族妇女CIN及宫颈鳞癌的转变过程中起一定的作用.     

Metastasierung von Malignomen des Uterus und therapeutische Konsequenzen

Malignancies of the uterus metastasize by direct invasion of neighboring structures, lymphatically or hematogenously. Endometrial and cervical cancers lymphatically spread to the pelvic and para-aortic lymph nodes. For endometrial cancer the depth of myometrial invasion, lymphosvascular space involvement (LVSI) and a microcystic, elongated and fragmented (MELF) glandular invasion pattern are predictors for lymph node metastases. Metastases to the pelvic lymph nodes occur in approximately 10?% of endometrial cancer patients and in 30?% of these cases the para-aortic lymph nodes are also involved. Sentinel lymph node biopsy is possible for clinical stage I endometrial cancer and early stages of cervical cancer but is not yet routine. The presence of LVSI is considered to be the strongest predictor of distant metastases, particularly if assessed by immunohistochemistry with antibodies against factor VIII-related antigen or CD31. Endometrioid and clear cell carcinomas can hematogenously metastasize to the lungs, bones, liver and brain and can rarely be manifested as a solitary metastasis. In contrast, serous carcinomas can show extensive peritoneal spread. To date molecular biomarkers cannot predict the occurrence of distant metastasis. Overexpression of P53, p16 and L1CAM have been identified as negative prognostic factors and are associated with the prognostically unfavorable serous tumor type. The metastatic spread of squamous cell cervical cancer is strongly associated with tumor volume. Microinvasive carcinomas have a very low rate of parametrial and lymph node involvement and do not require radical hysterectomy. In contrast, lymph node metastases occur in up to 50?% of bulky stages IB and II cervical cancers. Distant metastases can occur in the lungs, liver, bones and brain. Molecular biomarkers have not been shown to predict metastatic spread. In well-differentiated adenocarcinoma of the cervix the pattern of invasion is strongly predictive for the presence of lymph node metastases, irrespective of tumor size and depth of invasion.     

粒细胞集落刺激因子在非小细胞肺癌组织中的表达及其临床病理意义

目的 观察粒细胞集落刺激因子(G-CSF)在非小细胞肺癌(NSCLC)中的表达并探讨其临床病理意义.方法 收集解放军总医院2001 - 2010年伴有大量粒细胞浸润的NSCLC 53例,同时选用无粒细胞浸润的NSCLC 61例作对照,共114例.观察癌组织中粒细胞浸润情况,同时用免疫组织化学(EnVision法)检测癌组织中G-CSF的表达情况.对G-CSF表达情况及其与NSCLC临床病理特征的关系进行统计学分析,并随访全部患者,分析G-CSF表达对预后的影响.结果 114例NSCLC中55例癌细胞表达G-CSF.其中大细胞癌41例(41/54,75.9％),腺癌9例(9/30,30.0％),鳞状细胞癌5例(5/30,16.7％).G-CSF表达与癌组织中粒细胞浸润、组织学类型、坏死、肿瘤分级、局部淋巴结转移和远处转移、复发密切相关(P＜0.01),而与原发肿瘤大小无密切关联(P＞0.05);表达阳性者发生坏死、淋巴结转移、远处转移复发的相对危险度分别是阴性者的5.57、6.28和5.24倍(P＜0.05).阳性者与阴性者中位生存期分别为42和62个月,5年生存率分别为0和12.1％,生存期间的差异具有统计学意义(P＜0.01).结论 部分NSCLC能产生G-CSF,且以大细胞癌最常见.产生G-CSF的NSCLC组织分化差,异型性明显,恶性度高;易发生广泛坏死,常伴有粒细胞浸润;易发生淋巴结转移、远处转移和复发;生存率低,预后差.     

Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix.

Most cervical carcinomas appear to arise from cervical intraepithelial neoplasia (CIN) lesions. In addition to infection with high-risk human papilloma viruses, which is indicative of an increased risk of progression, alterations of oncogenes and tumor suppressor genes play a role. Genetic studies of CIN lesions, primary cervical carcinoma, and metastases may shed light on the relative importance of various genetic alterations involved in the progression of CIN to invasive carcinoma. We examined tumor material from 10 patients with squamous cell carcinoma of the uterine cervix and synchronous CIN lesions and lymph node metastases. The CIN component, invasive carcinoma, and lymph node metastases were analyzed separately for loss of heterozygosity (LOH) on the following loci: VHL (3p21), HLA region (6p22-23), PGL (11q 22-24), E6 associated protein (15q11-13), TP53 (17p13), DCC (18q21.1), and chromosomes 1, 2, 4, 9, 20, and X. Using immunohistochemistry, the expression of the EGF receptor, ERBB2, and TP53 was determined. In CIN lesions, frequent LOH was found at chromosome arms 3p, 6p, and 11q. Primary invasive carcinoma showed additional LOH at chromosome arms 6q, 17p, and 18q. In lymph node metastases, an additional locus on the X chromosome displayed LOH. All carcinomas and synchronous lesions but one showed high expression levels of the EGF receptor. TP53 staining, when present, was found in all synchronous lesions. Focal staining of ERBB2 was found in one CIN lesion, two invasive carcinomas, and four metastases. The molecular alterations accumulated in a fashion that paralleled the progression of the tumors. These results indicate that cervical tumorigenesis occurs in a stepwise fashion, including infection and integration of oncogenic HPV and several specific genetic alterations. Genes Chromosomes Cancer 26:346-354, 1999.     

The value of ultrasound in the assessment of cervical and abdominal lymph node metastases and selecting surgical strategy in patients with squamous cell carcinoma of the thoracic esophagus treated with neoadjuvant therapy

PurposeTo establish the role of ultrasound (US) in the assessment of cervical and abdominal lymph node metastases and its impact on making decision about surgical strategy in patients with squamous cell carcinoma of the thoracic esophagus.Material/MethodsThe results of US lymph node assessment before and after a neoadjuvant treatment in 83 patients were compared with the results of histopathological evaluation of lymph nodes harvested during surgery (transthoracic esophagectomy and 2-field extended or 3-field lymph node dissection). A diagnostic value of cervical and abdominal US in terms of sensitivity, specificity, positive and negative predictive value after a neoadjuvant treatment were determined.ResultsThe sensitivity, specificity, positive and negative predictive value of the US assessment of cervical lymph node metastases were 100%, 96%, 81% and 100%, respectively. The sensitivity, specificity, positive and negative predictive value of the US assessment of abdominal lymph node metastases were 82%, 94%, 91.5% and 87%, respectively.ConclusionsThe high sensitivity and specificity of cervical US make this investigational method sufficient in the assessment of cervical nodal involvement. In esophageal cancer patients with negative cervical lymph nodes on US, three-field lymph node dissection could be avoided. In patients with positive cervical lymph nodes on US one should consider to extend lymph node dissection about lymph nodes of the neck to achieve a curative resection. In patients with negative abdominal US this investigation should be supplemented by more detailed diagnostic methods.     

Impact of podoplanin expression in oral squamous cell carcinoma: clinical and histopathologic correlations

Cervical lymph node metastases reduce the overall survival of patients with oral squamous cell carcinoma (OSCC) and require a neck dissection. However, elective management of a clinical N0 neck remains a controversial topic, as there are no reliable factors available predicting cervical lymph node metastases. Recent studies suggest an impact of podoplanin expression on metastatic spread to the cervical lymph nodes. Our aim was to investigate the influence of podoplanin expression on prognosis and metastatic lymphatic spread. In our retrospective study, podoplanin expression was examined in a set of 80 patients with OSCC by immunhistochemistry. We analysed associations between the level of podoplanin expression and various clinicopathologic parameters. In 67 patients (84%), podoplanin was expressed on the tumour cells. Nineteen patients (24%) showed high levels of expression. The 5-year overall survival (31%) for patients with high levels of podoplanin expression was significantly lower (p < 0.001) than for patients with low and moderate expression of podoplanin (93% and 65%, respectively). There was an association between podoplanin expression and the frequency of cervical lymph node metastases. Cervical lymph node metastases were found in 79% of the patients with high podoplanin expression, while patients with weak podoplanin expression had metastases in only 22% (p < 0.001). None of the 13 patients without podoplanin expression had cervical lymph node metastases. We concluded that podoplanin is expressed frequently in OSCC and that podoplanin expression correlates with cervical lymph node metastases and clinical outcome.     

The probable origin of an anemone cell tumor: metastatic transitional cell carcinoma producing HCG

A neoplasm of unknown origin in cervical and axillary lymph nodes was diagnosed as anemone cell tumor by ultrastructural examination. Three years after the initial diagnosis of anemone cell tumor, a high-grade transitional cell carcinoma of the bladder was discovered. The results of immunoperoxidase staining of the cervical lymph node, axillary lymph node, and bladder tumors for keratin, carcinoembryonic antigen, and human chorionic gonadotropin (HCG) strongly suggest that the anemone cell tumors in this case represent metastases of bladder carcinoma cells capable of producing HCG.     

保留肋间臂神经对乳腺癌腋窝淋巴结清扫术的感觉障碍影响的研究

目的 探讨乳腺癌手术腋窝淋巴结清扫时保留肋间臂神经(ICBN)对感觉障碍影响的研究.方法 对146例Ⅰ、Ⅱ、Ⅲa期乳腺癌患者行改良根治术的临床资料进行分析.将其随机分为两组:保留组(67例)行腋窝淋巴结清扫术时保留ICBN,对照组(79例)行腋窝清扫时常规切除ICBN.比较两组在手术时间、腋窝淋巴结清扫数量及术后上臂内侧感觉异常等情况.结果 保留组及对照组术后1、3、6个月患侧上臂内侧感觉障碍发生率分别为17.9％、74.9％,11.9％、60.7％,7.4％、59.5％,差异均有统计学意义(x2=46.78,P＜0.001;x2=36.54,P＜0.001;x2=42.80,P＜0.001).手术时间及腋窝淋巴结清扫数量差异无统计学意义(P＞0.05).术后8个月到5年期间随访无局部复发.结论 对Ⅰ、Ⅱ、Ⅲa期乳腺癌患者在行腋窝淋巴结清扫时保留ICBN可明显减少术后患侧上臂内侧感觉障碍,从而提高生活质量,不影响局部复发率.     

Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model

Activation of matrix metalloproteinase-2 (MMP-2) is a common event in head and neck squamous cell carcinoma. An OSC-19 cell line, derived from human oral squamous cell carcinoma and known to metastasize to cervical lymph nodes, was implanted into the lingual margin of mice. The effect of marimastat (BB-2516), a broad MMP inhibitor, on the suppression of regional cervical lymph node metastasis was evaluated with an orthotopic implantation nude mice model. Marimastat was given immediately after OSC-19 implantation and continuously administered by an osmotic pump. The mice were divided into three groups by marimastat dose; Group A; 0 mg/kg/day, Group B; 30 mg/kg/day, and Group C; 150 mg/kg/day. Twenty-one days after implantation, primary oral tumors and cervical lymph nodes were resected. Cervical lymph node status was microscopically examined. Activation of MMP-2 in primary oral tumor was examined by gelatin zymography. Both cervical lymph node metastasis and activation of MMP-2 were significantly suppressed in Group C (P<0.05). Moreover, the Group C mice had a significantly better survival than group A (P=0.0026). There was a significant difference between Group A and Group C in terms of proliferation of tumor cells by proliferating cell nuclear antigen immunostaining (P=0.0120). These results suggest a positive role for marimastat in the inhibition of MMP-2 activation and prevention of cervical lymph node metastasis in oral squamous cell carcinoma (OSCC). Improvement of survival in patients with OSCC could be expected using adjuvant therapy with marimastat. This revised version was published online in July 2006 with corrections to the Cover Date.