CCR7和VEGF-C及微淋巴管密度与喉癌的淋巴结转移

发布时间：2018-03-14 16:27

本文选题：趋化因子受体CCR7　切入点：血管内皮生长因子-C(VEGF-C)　出处：《泸州医学院》2010年硕士论文　论文类型：学位论文

【摘要】： 目的：检测喉鳞状细胞癌(1 aryngeal squamous cell carcinoma, LSCC,简称喉鳞癌)、癌旁正常喉黏膜组织及喉部良性病变声带息肉组织中趋化因子受体CCR7 (C-C Chemokine Receptor 7,CCR7)及血管内皮生长因子-C(vascular endothelial growth factor,VEGF-C)的表达和微淋巴管密度值(lymphatic microvessel density,LMVD),并探讨三者间的相互关系及其与喉癌淋巴结转移的关系。方法：选取泸州医学院附属医院耳鼻咽喉-头颈外科2008年1月至2009年10月行手术切除并经病理检查诊断的40例喉部鳞状细胞癌的存档蜡块为实验组；40例癌旁正常喉黏膜组织(距癌组织5mm以上经病理证实为正常喉黏膜)及20例经病理检查证实为喉良性病变组织声带息肉为对照组。全部病例术前均行喉部高分辨率CT检查,且未行化疗或放疗。应用免疫组织化学方法检测以上组织中CCR7、VEGF-C及D2-40的表达,对D2-40阳性脉管进行LMVD计数,并结合临床病历资料进行统计学分析,分析CCR7、VEGF-C及LMVD与喉癌临床病理特征的关系,以及三者之间的相互关系。结果：喉癌组织与癌旁正常黏膜组织及声带息肉组织中CCR7的表达差异显著,CCR7主要表达于喉癌细胞的胞质和／或胞膜,阳性片可见胞质和／或胞膜上有棕黄色的片状物质,而在癌旁正常黏膜上皮少量阳性表达,在声带息肉组织中几乎无表达；40例喉癌组织中CCR7的表达阳性24例,阴性16例,阳性率60.0%(24/40), CCR7与喉癌淋巴结转移密切相关,而与患者性别、年龄、是否吸烟、细胞分化程度、临床分型及T分期无关。喉癌组织与癌旁正常黏膜组织及声带息肉组织中VEGF-C的表达差异显著(P0.05),VEGF-C的阳性染色为棕黄色,主要表达在喉癌细胞的胞浆内,声带息肉组织及阴性对照组中少量表达；40例喉癌组织中VEGF-C的表达阳性19例,阴性21例,阳性率47.5%(19／40),VEGF-C表达与肿瘤细胞分化程度、临床分型、T分期之间无显著性差异(P＞0.05),而淋巴结转移组阳性率及表达强度均高于非转移组,差异显著(P0.05)。D2-40较特异性地表达在淋巴管内皮细胞,呈棕黄色颗粒状,血管内皮细胞未见表达；喉癌组织癌巢内及外周间质均可见淋巴管被挤压成条索状,散在或成簇分布；喉癌组织与癌旁正常黏膜组织及声带息肉组织中微淋巴管密度差异显著(P0.05)；喉癌组织中微淋巴管密度在淋巴结转移组明显高于非转移组,差异非常显著(P0.01)。40例喉癌标本中,VEGF-C和CCR7均为阳性表达者有17例,均为阴性表达者有15例,Kappa一致性相关检验表明,喉癌组织中VEGF-C和CCR7表达有较高的吻合度(K=0.600),且二者间的吻合度有统计学意义(P=0.000)。VEGF-C表达阳性的组织中LMVD平均值为(17.57±3.27)个／mm2,表达阴性者LMVD平均值为(10.26±3.77)个／mm2,两者比较具有显著性差异(P0.05)。喉癌组织中CCR7阳性表达者LMVD为(19.05±5.33)个／mm2,阴性表达者LMVD为(11.16±5.28)个／mm2,两者相比,P0.01。结论：(1) CCR7与喉癌的淋巴结转移有关,VEGF-C与喉癌的淋巴管生成有关,两者具有协同作用,共同促进喉癌细胞的淋巴结转移；(2)D2-40标记淋巴管的特异性和敏感性较好,是新近发现较为理想的淋巴管标记物,喉癌组织及边缘区高LMVD与淋巴结转移之间呈明显相关,提示淋巴管生成在喉癌淋巴结转移中具有重要作用；(3)随着CCR7表达强度的增加VEGF-C阳性分级随之上升,LMVD均值也逐渐增加,LMVD均值的增加是与CCR7阳性强度平行的,即CCR7表达越强,LMVD均值越高,CCR7、VEGF-C与LMVD之间呈显著相关性；(4) CCR7、VEGF-C和LMVD与喉癌的淋巴结转移密切相关,联合检测它们在内镜活检组织中的表达有助于预测喉癌早期淋巴结转移的发生。
[Abstract]:Objective: to detect laryngeal squamous cell carcinoma (1 aryngeal squamous cell carcinoma LSCC, referred to as laryngeal squamous cell carcinoma), chemokine receptor CCR7 in adjacent normal laryngeal mucosa tissues and laryngeal benign lesions of vocal cord polyp tissues (C-C Chemokine Receptor 7, CCR7) and vascular endothelial growth factor -C (vascular endothelial growth factor, VEGF-C). Expression and lymphatic microvessel density (lymphatic value microvessel density, LMVD), and to explore the relationship between the three and their relationship with lymph node metastasis of laryngeal carcinoma. Methods: paraffin blocks for the experimental group selected 40 cases of laryngeal squamous cell carcinoma of Otolaryngology Head and neck surgery in Affiliated Hospital of Luzhou Medical College from January 2008 to October 2009 underwent surgical resection and confirmed by pathological examination diagnosis; 40 cases of adjacent normal laryngeal mucosa tissue (5mm away from cancer tissue than normal laryngeal mucosa was confirmed by pathology) and 20 cases of pathologically confirmed Laryngeal Benign check Lesions of vocal cord polyps were treated as control group. The throat of high resolution CT examination in all cases before surgery, and without chemotherapy or radiotherapy. CCR7 immunohistochemical method was used to detect the expression of VEGF-C and D2-40 in the LMVD to count the number of D2-40 positive vessels, and combined with the clinical medical records data for statistical analysis, analysis CCR7, VEGF-C and LMVD and clinical features of laryngeal squamous cell carcinoma, and the relationship between the three. Results: the expression of CCR7 in laryngeal carcinoma and adjacent normal mucosa tissue and vocal cord polyp tissues significantly, cytoplasmic CCR7 is mainly expressed in laryngeal carcinoma cells and / or cell membrane, flaky material and brown yellow positive film cytoplasm and / or on the cell membrane, and in adjacent normal mucosa showed positive expression in vocal cord polyps almost no expression; 24 cases of positive expression of CCR7 in 40 cases of laryngeal carcinoma, 16 cases of yin and Yang The rate of 60% (24/40), CCR7 and lymph node metastasis in laryngeal cancer is closely related with gender, age, smoking, cell differentiation, clinical typing and staging of T. The differential expression of VEGF-C in laryngeal carcinoma and adjacent normal mucosa tissues and vocal polyp tissues showed positive staining (P0.05), VEGF-C brown, mainly expressed in the cytoplasm of laryngeal squamous cell carcinoma and polyp of vocal cord and negative control group in a small amount of expression; 19 cases of positive expression of VEGF-C in 40 cases of laryngeal carcinoma, 21 cases were negative, the positive rate was 47.5% (19 / 40), and the degree of differentiation of tumor cell VEGF-C expression, clinical classification, T significant differences between stages (P > 0.05), and lymph node metastasis group the positive rate and expression intensity were higher than those in the non metastasis group, significant difference (P0.05).D2-40 is specifically expressed in lymphatic endothelial cells, brownish yellow granules, expression of vascular endothelial cells; larynx Cancer nests and peripheral lymphatic interstitial were observed by extrusion into cords, scattered or clustered; laryngeal cancer tissue and adjacent normal mucosa and polyp of vocal cord lymphatic microvessel density in significant difference (P0.05) in laryngeal carcinoma; lymphatic microvessel density in lymph node metastasis group higher than the non metastatic group was significant difference (P0.01).40 cases of laryngeal carcinoma specimens, VEGF-C and CCR7 were positive expression in 17 cases were negative expression in 15 cases, Kappa consistency test showed that the agreement had higher VEGF-C and CCR7 expression in laryngeal squamous cell carcinoma (K=0.600), and the two the agreement was statistically significant (P=0.000).VEGF-C expression in LMVD positive tissues average (17.57 + 3.27) / mm2, negative expression of the average LMVD (10.26 + 3.77) / mm2, compared with significant difference (P0.05). The positive expression of CCR7 in laryngeal carcinoma LM VD (19.05 + 5.33) / mm2, the negative expression of LMVD (11.16 + 5.28) / mm2, P0.01. comparison, conclusion: (1) CCR7 laryngeal carcinoma and lymph node metastasis, VEGF-C and laryngeal cancer lymphangiogenesis, they have synergistic effect, promote lymph cells of laryngeal carcinoma node metastasis; (2) good D2-40 markers of lymphatic specificity and sensitivity, is a newly found ideal lymphatic markers, was significantly related between laryngeal carcinoma and the marginal zone of high LMVD and lymph node metastasis, suggesting that lymphangiogenesis plays an important role in lymph node metastasis in laryngeal carcinoma; (3) the expression of CCR7 increase the strength of VEGF-C positive grading increased, LMVD value increased gradually, increasing the mean value of LMVD is in parallel with the CCR7 positive intensity, the more expression of CCR7, LMVD value is higher, CCR7, between VEGF-C and LMVD showed a significant correlation; (4) CCR7, VEGF-C and LMVD and laryngeal The lymph node metastasis of cancer is closely related. The joint detection of their expression in endoscopic biopsy tissue is helpful to predict the occurrence of early lymph node metastasis in laryngeal carcinoma.

【学位授予单位】：泸州医学院
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R739.65

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