【作者】 张华；

【导师】 田铧；

【作者基本信息】 山东大学 ， 人体解剖与组织胚胎学， 2011， 硕士

【摘要】 研究背景：肿瘤细胞的生长、侵袭和转移涉及到肿瘤细胞的趋化、细胞外基质的破坏等多种因素。最近的研究发现,趋化因子受体7(chemokine receptor 7, CCR7)在某些肿瘤的转移、发展过程中起重要作用,而且据文献报道：在多种肿瘤中CCR7能上调肿瘤细胞对基质金属蛋白酶-9(matrix metalloproteinases-9, MMP-9)的表达,因此CCR7与MMP-9有可能在肿瘤侵袭、转移过程中发挥协同作用。甲状腺乳头状癌(papillary thyroid cancers, PTCs)是头颈外科中最常见的恶性肿瘤之一,极易发生淋巴转移。但目前关于CCR7在PTCs的表达情况报道甚少,CCR7和MMP-9的表达是否存在相互关系也未见报道。该研究对于探寻PTCs转移趋势的判断指标和药物的靶向治疗等研究具有重要的临床应用意义。目的：研究CCR7和MMP-9在PTCs和转移淋巴结组织中的表达,探讨PTCs中CCR7和MMP-9表达的关系及其与临床病理参数的关系,探寻判断PTCs转移趋势和预后评估的生物学指标。方法：收集山东大学齐鲁医院2008年—2010年行PTCs根治术的组织标本60例、转移淋巴结标本26例。采用免疫组织化学SP法检测肿瘤组织、转移淋巴结组织以及癌旁正常甲状腺组织中CCR7和MMP-9的表达。在高倍镜下观察切片的10个代表区,每个视野随机计数100个细胞,并计算阳性细胞百分数,以染色强度和阳性细胞百分数的乘积作为CCR7和MMP-9的表达量,应用SPSS12.00软件对结果进行统计学分析,探讨CCR7和MMP-9的表达情况、表达关系及其与临床病理参数的相关性。结果：①CCR7在60例PTCs组织中阳性表达率为56.7%(34/60),在癌旁正常组织中不表达(0/60),两者的差异具有非常显著的统计学意义(P<0.01)；其中在淋巴结转移组,原发灶阳性表达率为92.3%(23/26),显著高于无淋巴结转移组的阳性表达率29.4%(10/34)(P<0.05)；CCR7的表达率与淋巴结转移密切相关,与患者的年龄、性别和肿瘤大小无关P>0.05).②MMP-9在60例PTCs组织中阳性表达率为70.0%(42/60),显著高于癌旁甲状腺正常组织的阳性表达率6.67%(4/60)(P<0.01)；其中淋巴结转移组的原发灶阳性表达率为92.3%(24/26),显著高于无淋巴结转移组的阳性表达率52.9%(18/34)(P <0.05);MMP-9的阳性表达与淋巴结转移密切相关,与患者的年龄、性别和肿瘤大小无关(P>0.05)。③CCR7在26例转移淋巴灶中的阳性表达率为69.2%(18/26),其中18例与原发灶同步表达,6例原发灶呈阳性表达而淋巴结转移灶内呈阴性表达,2例为淋巴结转移灶和原发灶均呈阴性表达,即转移灶中的表达率有所降低。④MMP-9在26例转移淋巴灶中的阳性表达率为92.3%(24/26),其中22例与原发灶同步表达,2例原发灶为阳性而淋巴结转移灶呈阴性表达,2例原发灶为阴性而淋巴结转移灶内呈阳性表达。⑤无论是在原发灶还是转移灶中,CCR7的表达和MMP-9的表达存在明显的正相关关系(P<0.05)。⑥CCR7仅表达于肿瘤细胞的细胞浆或细胞膜上,在癌周围正常甲状腺组织和间质细胞不表达；而MMP-9则可表达于肿瘤细胞的细胞浆或周围的细胞外基质中。结论：①CCR7和MMP-9在PTCs组织中呈高表达,CCR7的表达具有高度的肿瘤细胞特异性；②原发灶CCR7和MMP-9的表达与淋巴结转移明显相关,而与患者的性别、年龄和肿瘤的大小无关；③淋巴结转移灶中MMP-9表达率与原发灶相当,但CCR7的表达率较原发灶降低；④CCR7和MMP-9的阳性表达存在明显的正相关关系。更多还原

【Abstract】 Backgrounds:Tumor cell growth, invasion and metastasis require multiple steps to complete, including chemotaxis of tumor cell, extracellular matrix and basement membrane’s disorder. According to recent research, chemokine receptor 7 (CCR7) plays a pivotal role in tumoral invasion and metastasis in part by up-regulating the expression of matrix metalloproteinase 9 (MMP-9) in tumor cells. The papillary thyroid cancers(PTCs), which mainly metastasizes through lymphatic pathway, is one of the most common malignant tumors in Head and Neck Surgery. However, the expression of CCR7 in PTCs has hardly been reported, nor its relationship with MMP-9, the study of which would be of a promising significance in the assessment of the metastatic tendency and the target therapy for PTCs.Objectives:To investigate the expression of CCR7 and MMP-9 in PTCs and metastatic lymph node, and evaluate their relationship to the pathology and metastasis of PTCs.Methods:Papillary thyroid cancer specimens 60 cases from papillary thyroid cancer patients and 26 cases of metastatic lymph nodes in 2008-2009 were randomly collected from Qilu Hospital of Shandong University. The expression of CCR7 and MMP-9 were detected by the SP method of immunochemistry in both thyroid tissues and corresponding metastatic lymph nodes.10 fields of observation were randomly chosen under microscope 400X in magnification. The percentage of positive cells was calculated and the intensity of staining was also graded according to the degree of coloration. Their cross products were used as the final score of expression and analyzed with SPSS 12.00 software.Results:①CCR7 was expressed in 56.7%(34/60) of the patients, higher than that in normal tissues 0%(0/60) (P<0.01). The expression rate of CCR7 in metastatic lymph nodes was 92.3%(23/26), also higher than that in non-metastatic lymph nodes 29.4%(10/34) (P<0.05). The expression of CCR7 in PTCs was significantly associated with lymph-node metastasis, but with no relation to age, gender or tumor size (P>0.05);②MMP-9 was expressed in 70.0%(42/60) of the patients, higher than that in normal tissues 6.67%(4/60) (P<0.01). The expression rate of MMP-9 in metastatic lymph nodes was 92.3%(24/26), higher than that in non-metastatic lymph nodes 52.9%(18/34) (P<0.05). The expression of MMP-9 in PTCs was closely associated with lymph-node metastasis, without significant variation in age, gender or tumor size (P>0.05);③The expression rate of CCR7 in the 26 lymph node metastasis cases is 69.2%(18/26):18 cases expressed CCR7 in thyroid tissues and lymph node tissues,6 negative in lymph node but positive in thyroid tissue, and 2 negative in both tissues;④The expression rate of MMP-9 in 26 metastatic lymph node is 92.3%(24/26), with 22 cases expressing MMP-9 in both tissues,2 only positive in lymph nodes but negative in thyroid tissues, the other 2 only positive in thyroid tissues;⑤No matter in which tissues, thyroid glands or metastatic lymph nodes, the expression of CCR7 is in direct proportion to the expression of MMP-9 (P <0.05);⑥CCR7 was strictly expressed on the surface or in the cytoplasma of the tumor cells, but negative in the peritumoral tissues; On the other hand, MMP-9 was occasionally detected in the normal tissues which surrounded the tumor.Conclusion:①CCR7 and MMP-9 were abundantly expressed in PTCs; CCR7 expression was highly specific for the tumor cells.②CCR7 and MMP-9 expressions by PTCs were both closely related to the lymph node metastasis, but not to the patient age, sex and tumor size.③The percentage of MMP-9 expression in lymph node metastasis was correspond to that in PTCs, but that of CCR7 expression in lymph metastasis was decreased.④The expression of CCR7 and MMP-9 were positive correlation relationship.更多还原