肺鳞癌间质中CAFs与LVD、MVD的关系及其临床意义

发布时间：2018-03-22 07:46

本文选题：肺鳞状细胞癌　切入点：FAP-1　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:本文观察肺鳞状细胞癌的间质中被成纤维细胞激活蛋白1(FAP-1)染色的肿瘤相关成纤维细胞(CAFs),研究其与间质中微血管密度(MVD)、淋巴管密度(LVD)的关系,探讨CAFs对肺鳞状细胞癌患者的总生存期(OS)的影响。方法:本研究选择63例肺鳞状细胞癌标本为研究对象,均来自于2011年1月份至2012年12月份在青岛市市立医院的胸外科行肺切除术的患者,所获得的病例中男性为58例,女性为5例。根据第七版美国癌症联合会(AJCC)的TNM分期原则对所选择的所有63例病例进行分期:I期为29例,Ⅱ期为19例,Ⅲ期为15例。所选病例的组织切片分别进行兔抗人FAP-1多克隆抗体的免疫组织化学法染色,鼠抗人原始造血细胞(CD34)单克隆抗体的免疫组织化学法染色,鼠抗人D2-40单克隆抗体的免疫组织化学法染色,在病理专家的阅片后进行评估。根据肿瘤间质中阳性着色细胞的百分比来对肿瘤相关成纤维细胞进行FAP-1着色的评估,再依据着色细胞所占的比例判定分数:0=没有着色;1=1%-10%;2=11%-50%;3"g50%。在本研究中采用50%作为分割点,FAP-1评分高于3时被认为是高表达,即为CAFs丰富组,低于3分为低表达,即为CAFs贫乏组。对于淋巴管的要求为,镜下观察只要与周边的其他组织存在有较为明确的界限的任何一个细胞质内呈棕色染色的内皮细胞或内皮细胞群,均规定称之为间质内的一条淋巴管。对于微血管的要求为,任何一个细胞质内成淡黄色或棕黄色的内皮细胞或内皮细胞簇,而且与周边环境内肿瘤细胞及结缔组织成分有明显分界的,则规定算作为间质内的一条微血管。两者分别取4个视野的读数的均值作为LVD、MVD。在本研究中对所选取的所有63例术后患者进行规范的密切的跟随访查,跟随访查的最终时间结束于2015年12月31日。在本研究中所获得的全部数据应用SPSS 17.0软件进行相应处理,对CAFs与LVD、CAFs与MVD、CAFs与各临床病理因素之间关系的研究均采用卡方检验进行分析;对于总生存期的预后评估,应用Cox比例风险模型进行分析。P0.05为差异有统计学意义。结果:FAP-1的表达定位于肿瘤间质细胞内,以50%作为分界点,CAFs丰富组即FAP-1高表达组为27例,CAFs贫乏组即FAP-1低表达组为36例;肺鳞状细胞癌的间质内CAFs与肺鳞状细胞癌患者有无淋巴结转移,与患者的肿瘤细胞的分化程度有关,差异具有统计学意义(P㩳0.05),而与肺鳞状细胞癌患者的性别、年龄,是否吸烟、TNM分期均无关,差异无统计学意义(P0.05);肺鳞状细胞癌患者间质内CAFs丰富组的微血管密度相比较于贫乏组的微血管密度要高,此差异具有统计学意义(P㩳0.05);肺鳞状细胞癌患者间质内CAFs丰富组的淋巴管密度相比较于贫乏组的淋巴管密度要高,此差异具有统计学意义(P㩳0.05);肺鳞状细胞癌患者的三年总生存期(OS)与间质内CAFs的密度相关,差异具有统计学意义(P㩳0.05);肺鳞状细胞癌患者的三年总生存期(OS)与淋巴结是否转移淋巴结转移相关,差异具有统计学意义(P㩳0.05)。结论:本研究表明肺鳞状细胞癌间质中CAFs与LVD、MVD的增加呈显著相关,肺鳞状细胞癌间质内的CAFs是肺鳞状细胞癌患者不良预后的一重要影响因素。
[Abstract]:Objective: To observe the lung squamous cell carcinoma by interstitial fibroblast activation protein 1 (FAP-1) staining of tumor associated fibroblasts (CAFs), and study the microvessel density in the stroma (MVD), lymphatic vessel density (LVD) relationship, on overall survival of patients with lung squamous cell cancer CAFs (OS) effect. Methods: This study selected 63 cases of lung squamous cell carcinoma specimens as the research object, from 2011 January to 2012 December in Qingdao Municipal Hospital Department of thoracic surgery underwent pulmonary resection obtained in cases of male 58 cases, female 5 cases according to the article. Seventh edition of the American Joint Committee on cancer (AJCC) TNM staging principle for all 63 cases selected for stage I 29 cases, 19 cases of stage II, III 15 cases. Immunohistochemical tissue sections were selected cases of Rabbit anti human FAP-1 polyclonal antibody histochemical staining. Mouse anti human primary The beginning of hematopoietic stem cells (CD34) immunohistochemistry of monoclonal antibody staining, immunohistochemistry of mouse anti human D2-40 monoclonal antibody staining, evaluated in reading experts. According to the pathological evaluation the percentage of positive cells in tumor stroma to tumor associated fibroblasts by FAP-1 staining, then according to the for coloring the proportion of cells scores: 0= 1=1%-10%; 2=11%-50%; no coloring; 3 "g50%. 50% used in this research as the dividing point, FAP-1 score higher than 3 is considered high expression, namely CAFs rich group, less than 3 for the low expression of CAFs is poor for lymphatic requirements group. As observed any cytoplasm as long as there is with other organizations around the boundaries clear in brown staining of endothelial cells or cells, are called a shower set interstitial Pakistan pipe for micro blood. The requirements for endothelial cells or cell clusters in the cytoplasm of any light yellow or brown yellow, and the composition and surrounding environment within tumor cells and connective tissue has obvious boundary, provides regarded as interstitial microvascular. A mean respectively take 4 vision readings as LVD, MVD. in the study of the selected 63 cases of all patients were closely follow the norms established following the final visit time ended in December 31, 2015. Obtained in this study all the data using SPSS 17 software processed, CAFs and LVD, CAFs and MVD, study the relationship between CAFs and the clinicopathological factors were analyzed by chi square test; prognosis for overall survival, Cox proportional hazard model was used for analysis of.P0.05 difference was statistically significant. Results: the expression of FAP-1 in tumor Tumor interstitial cells, with 50% as cut-off point, CAFs rich group which is the high expression of FAP-1 group was 27 cases, CAFs group is the lack of FAP-1 low expression group was 36 cases; patients with squamous cell carcinoma of the lung interstitial CAFs and squamous cell carcinoma of the lung and lymph node metastasis, differentiation degree and patients the tumor cells, the difference was statistically significant (P? 0.05), and patients with lung squamous cell carcinoma of the gender, age, smoking, TNM stage were independent, no statistically significant difference (P0.05); microvessel density in patients with squamous cell carcinoma of lung interstitial CAFs rich group compared to the poor group of micro the vascular density is higher, the difference was statistically significant (P? 0.05); lung squamous cell carcinoma patients with interstitial CAFs rich group of lymphatic vessel density compared to the poor group of lymphatic vessel density is higher, the difference was statistically significant (P? 0.05); three years overall survival in patients with squamous cell carcinoma of the lung. (OS) With interstitial CAFs density, the difference was statistically significant (P? 0.05); three years overall survival in patients with lung squamous cell carcinoma (OS) and lymph node metastasis of lymph node metastasis, the difference was statistically significant (P? 0.05). Conclusion: This study suggests that interstitial lung squamous cell carcinoma CAFs and LVD were significantly related to increased MVD, squamous cell carcinoma of the lung interstitial CAFs is an important influencing factor of poor prognosis in patients with squamous cell carcinoma of the lung.

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R734.2

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