调强放疗技术下鼻咽癌侵袭性标志物表达对其疗效预测的意义
发布时间：2018-09-12 13:59
【摘要】：研究背景与目的：上皮-间质转化(EMT)是恶性肿瘤浸润和转移的重要机制,肿瘤内新生血管和淋巴管的形成与肿瘤浸润转移密切相关,肿瘤细胞通过EMT获得侵袭与转移的能力,侵入肿瘤新生血管与淋巴管内,完成内侵袭过程。本研究观察上皮-间质转化相关标志物E-cad, N-cad及CD34标记的微血管和D2-40标记的淋巴管在鼻咽癌组织中的表达情况及其相互关系,分析其与鼻咽癌临床病理特征的关系及与转移复发和预后的关系,进一步研究这些侵袭性标志物与放疗局控率的关系及调强放疗对这些标志物高危表达的逆转趋势,初步探讨它们在鼻咽癌发展中的作用及其临床应用价值。 方法：对160例鼻咽癌组织标本采用免疫组织化学方法同期检测E-cad、N-cad、CD34和D2-40表达,通过计算机辅助图像分析系统定量分析其表达情况,与临床病理资料作对照,研究其与鼻咽癌临床病理特征的关系,通过Spearman秩相关分析这些指标在鼻咽癌中表达的相关性。对接受常规放射治疗的77例患者进行治疗后随访,通过单因素和Logistic多因素回归分析筛选鼻咽癌复发转移的独立风险因素,Kaplan-Meier法和Log-rank检验上皮-间质转化相关标志物与鼻咽癌的预后关系。对接受调强放射治疗的83例患者,通过精确概率法分析E-cad、N-cad, D2-40与CD34表达与鼻咽部肿瘤体积退缩情况的关系。 结果： 1、侵袭性标志物检测结果：E-cad蛋白主要表达于细胞膜和细胞浆,呈棕黄或棕褐色,阳性细胞弥漫或局灶性分布,在鼻咽癌组织中表达的免疫组化阳性指数(IHCPI)为1.250±0.454(95%区间1.182～1.315)；N-cad蛋白主要在细胞膜和细胞质表达,呈棕黄色至深褐色弥散性分布,IHCPI为0.735±0.338(95%区间0.684～0.785)；D2-40标记的淋巴管呈一致性的管腔结构,呈棕黄色染色,表现为一层薄壁,管腔内很少有淋巴细胞,无红细胞,IHCPI为0.122±0.127(95%区间0.102-0.141)；CD34标记的微血管可见染色清晰的血管内皮细胞,呈棕黄色至深褐色弥散性分布,管腔大小不一,IHCPI为0.116±0.061(95%区间0.106～0.125)。E-cad表达下调、N-cad表达上调与鼻咽癌的淋巴结转移、肿瘤分期和复发转移具有密切关系,CD34表达与肿瘤分期有关,D2-40表达与淋巴管转移有关；这些指标表达与患者的年龄和性别均无显著意义(P0.05)。Spearman秩相关检验显示E-cad与N-cad,以及E-cad与D2-40表达呈明显负相关,CD34和D2-40表达旱明显正相关。 2、侵袭性标志物表达与鼻咽癌复发转移相关性分析：单因素分析显示E-cad,N-cad, CD34和D2-40表达与鼻咽癌复发转移相关(P0.05)。多因素分析显示E-cad和C934是影响鼻咽癌复发转移的独立风险因素。E-cad下调,N-cad、CD34和D2-40上调的鼻咽癌病人预后差,反之亦然。 3、侵袭性标志物表达与鼻咽癌放疗结果分析：精确概率法分析显示70Gy时鼻咽癌原发灶和颈淋巴结退缩均高于50Gy时；调强放疗组肿瘤体积退缩率高于常规放疗组,差异有统计学意义(P0.05)；E-cad高表达较E-cad1(?)表达、V-cad低表达较N-cad高表达组鼻咽部肿瘤退缩好,差异有统计学意义(P0.05)。在CD34高表达组中,常规放疗与调强放疗对肿瘤的退缩率无明显差异(P0.05)；在CD34低表达组中,调强放疗组对肿瘤退缩率高于与常规放疗组(P0.05)。在D2-40高表达组中,常规放疗与调强放疗对肿瘤的退缩率无明显差异(P0.05)；在D2-40低表达组中,调强放疗组对肿瘤退缩率高于与常规放疗组(P0.05)。 结论：鼻咽癌组织中存在EMT现象,E-cad蛋白在鼻咽癌中低表达,而N-cad蛋白在鼻咽癌中高表达,可能存在E-cad向N-cad转化；鼻咽癌基质内存在新生淋巴管和微血管,新生淋巴管与淋巴结转移相关,新生微血管与肿瘤T分期和临床分期相关。联合检测E-cad、N-cad、CD34和D2-40对于鼻咽癌侵袭转移和预后有一定的预测价值。在早期鼻咽癌患者中调强放疗技术对肿瘤的局控率与常规放疗技术相仿,提示是否可适当下调每次分割剂量,有利进一步保护肿瘤周围正常组织；在局部晚期鼻咽癌患者中,调强放疗技术对肿瘤的局控率高于常规放疗技术。调强放疗技术增加了局部晚期鼻咽癌患者中CD34和D2-40低表达组的肿瘤退缩率,考虑是调强放疗技术可能因为增加了每次分割剂量,从而提高了肿瘤杀伤效率。在鼻咽癌侵袭性标志物不同表达的患者中,调强放疗技术对肿瘤的局控率均高于常规放疗技术,因此推测调强放疗技术可能存在逆转相关侵袭性过程。
[Abstract]:BACKGROUND AND OBJECTIVE: Epithelial-mesenchymal transition (EMT) is an important mechanism of invasion and metastasis of malignant tumors. The formation of neovascularization and lymphatic vessels in tumors is closely related to tumor invasion and metastasis. Tumor cells acquire the ability of invasion and metastasis through EMT, invade tumor neovascularization and lymphatic vessels, and complete the process of internal invasion. Expression of E-cad, N-cad, CD34-labeled microvessels and D2-40-labeled lymphatics in nasopharyngeal carcinoma tissues and their relationship with clinicopathological features, metastasis, recurrence and prognosis were analyzed. The relationship between these invasive markers and local control rate of radiotherapy was further studied. The reversal trend of high-risk expression of these markers by relational and intensity-modulated radiotherapy (IMRT) was studied. The role of IMRT in the development of nasopharyngeal carcinoma and its clinical value were discussed.
Methods: The expression of E-cad, N-cad, CD34 and D2-40 in 160 nasopharyngeal carcinoma tissues was detected by immunohistochemistry. The expression of E-cad, N-cad, CD34 and D2-40 was quantitatively analyzed by computer-aided image analysis system. The relationship between E-cad, N-cad, CD34 and D2-40 expression and clinicopathological features of nasopharyngeal carcinoma was studied by comparing with clinicopathological data. The independent risk factors for recurrence and metastasis of nasopharyngeal carcinoma were screened by univariate and logistic multivariate regression analysis. Kaplan-Meier method and Log-rank method were used to examine the relationship between epithelial-mesenchymal transition-related markers and the prognosis of nasopharyngeal carcinoma. The relationship between the expression of E-cad, N-cad, D2-40 and CD34 and the volume regression of nasopharyngeal tumors was analyzed by exact probability method in 83 patients with IMRT.
Result:
1. Invasive markers: E-cad protein was mainly expressed in the cell membrane and cytoplasm, brown or brown, positive cells were diffuse or focal distribution, the expression of immunohistochemical positive index (IHCPI) in nasopharyngeal carcinoma tissue was 1.250 (+ 0.454) (95% range 1.182-1.315); N-cad protein was mainly expressed in the cell membrane and cytoplasm, showing brown. Yellow to dark brown diffuse distribution, IHCPI 0.735 (+ 0.338) (95% range 0.684 ~0.785); D2-40 labeled lymphatic vessels were uniform lumen structure, showing a brown-yellow staining, a thin wall, few lymphocytes in the lumen, no red blood cells, IHCPI 0.122 (+ 0.127) (95% range 0.102-0.141); CD34 labeled microvessels showed clear staining. The clear vascular endothelial cells were brown-yellow to dark-brown diffusely distributed with different lumen sizes. IHCPI was 0.116 (+ 0.061) (95% range 0.106-0.125). E-cad expression was down-regulated, N-cad expression was up-regulated and closely related to lymph node metastasis, tumor stage and recurrence and metastasis, CD34 expression was related to tumor stage, D2-40 expression was related to lymphatic metastasis. Spearman rank correlation test showed that E-cad was negatively correlated with N-cad, E-cad was negatively correlated with D2-40 expression, and CD34 and D2-40 were positively correlated with drought.
2. Correlation between expression of invasive markers and recurrence and metastasis of nasopharyngeal carcinoma: Univariate analysis showed that expression of E-cad, N-cad, CD34 and D2-40 was associated with recurrence and metastasis of nasopharyngeal carcinoma (P 0.05). Multivariate analysis showed that E-cad and C934 were independent risk factors for recurrence and metastasis of nasopharyngeal carcinoma. The prognosis is poor, and vice versa.
3. Expression of invasive markers and results of radiotherapy for nasopharyngeal carcinoma: Precise probability analysis showed that the primary lesion and cervical lymph node shrinkage of nasopharyngeal carcinoma at 70 Gy was higher than that at 50 Gy; the tumor volume shrinkage rate of IMRT group was higher than that of conventional radiotherapy group, the difference was statistically significant (P 0.05); E-cad expression was higher than that of E-cad1 (?), V-cad expression was lower than that of N-cad. There was no significant difference between conventional radiotherapy and intensity modulated radiotherapy (P 0.05). In the low expression group, intensity modulated radiotherapy had a higher rate of tumor regression than conventional radiotherapy (P 0.05). In the high expression group, conventional radiotherapy and intensity modulated radiotherapy had a higher rate of tumor regression than conventional radiotherapy (P 0.05). There was no significant difference in tumor shrinkage rate between the two groups (P 0.05), but in the low expression group of D2-40, the rate of tumor shrinkage in IMRT group was higher than that in conventional radiotherapy group (P 0.05).
Conclusion: EMT exists in nasopharyngeal carcinoma tissues, E-cad protein is low expressed in nasopharyngeal carcinoma, and N-cad protein is high expressed in nasopharyngeal carcinoma, which may lead to the transformation from E-cad to N-cad. Combined detection of E-cad, N-cad, CD34 and D2-40 has certain predictive value for invasion, metastasis and prognosis of nasopharyngeal carcinoma. In early stage nasopharyngeal carcinoma patients, the local control rate of IMRT is similar to that of conventional radiotherapy, suggesting whether proper dose reduction of each dose is beneficial to protect the surrounding normal tissues. Intensity modulated radiation therapy (IMRT) can increase the tumor regression rate in locally advanced nasopharyngeal carcinoma (NPC) patients with low expression of CD34 and D2-40. In patients with different expression of invasive markers, intensity modulated radiation therapy (IMRT) has a higher tumor control rate than conventional radiotherapy, so IMRT may reverse the invasive process.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R739.63
[Abstract]:BACKGROUND AND OBJECTIVE: Epithelial-mesenchymal transition (EMT) is an important mechanism of invasion and metastasis of malignant tumors. The formation of neovascularization and lymphatic vessels in tumors is closely related to tumor invasion and metastasis. Tumor cells acquire the ability of invasion and metastasis through EMT, invade tumor neovascularization and lymphatic vessels, and complete the process of internal invasion. Expression of E-cad, N-cad, CD34-labeled microvessels and D2-40-labeled lymphatics in nasopharyngeal carcinoma tissues and their relationship with clinicopathological features, metastasis, recurrence and prognosis were analyzed. The relationship between these invasive markers and local control rate of radiotherapy was further studied. The reversal trend of high-risk expression of these markers by relational and intensity-modulated radiotherapy (IMRT) was studied. The role of IMRT in the development of nasopharyngeal carcinoma and its clinical value were discussed.
Methods: The expression of E-cad, N-cad, CD34 and D2-40 in 160 nasopharyngeal carcinoma tissues was detected by immunohistochemistry. The expression of E-cad, N-cad, CD34 and D2-40 was quantitatively analyzed by computer-aided image analysis system. The relationship between E-cad, N-cad, CD34 and D2-40 expression and clinicopathological features of nasopharyngeal carcinoma was studied by comparing with clinicopathological data. The independent risk factors for recurrence and metastasis of nasopharyngeal carcinoma were screened by univariate and logistic multivariate regression analysis. Kaplan-Meier method and Log-rank method were used to examine the relationship between epithelial-mesenchymal transition-related markers and the prognosis of nasopharyngeal carcinoma. The relationship between the expression of E-cad, N-cad, D2-40 and CD34 and the volume regression of nasopharyngeal tumors was analyzed by exact probability method in 83 patients with IMRT.
Result:
1. Invasive markers: E-cad protein was mainly expressed in the cell membrane and cytoplasm, brown or brown, positive cells were diffuse or focal distribution, the expression of immunohistochemical positive index (IHCPI) in nasopharyngeal carcinoma tissue was 1.250 (+ 0.454) (95% range 1.182-1.315); N-cad protein was mainly expressed in the cell membrane and cytoplasm, showing brown. Yellow to dark brown diffuse distribution, IHCPI 0.735 (+ 0.338) (95% range 0.684 ~0.785); D2-40 labeled lymphatic vessels were uniform lumen structure, showing a brown-yellow staining, a thin wall, few lymphocytes in the lumen, no red blood cells, IHCPI 0.122 (+ 0.127) (95% range 0.102-0.141); CD34 labeled microvessels showed clear staining. The clear vascular endothelial cells were brown-yellow to dark-brown diffusely distributed with different lumen sizes. IHCPI was 0.116 (+ 0.061) (95% range 0.106-0.125). E-cad expression was down-regulated, N-cad expression was up-regulated and closely related to lymph node metastasis, tumor stage and recurrence and metastasis, CD34 expression was related to tumor stage, D2-40 expression was related to lymphatic metastasis. Spearman rank correlation test showed that E-cad was negatively correlated with N-cad, E-cad was negatively correlated with D2-40 expression, and CD34 and D2-40 were positively correlated with drought.
2. Correlation between expression of invasive markers and recurrence and metastasis of nasopharyngeal carcinoma: Univariate analysis showed that expression of E-cad, N-cad, CD34 and D2-40 was associated with recurrence and metastasis of nasopharyngeal carcinoma (P 0.05). Multivariate analysis showed that E-cad and C934 were independent risk factors for recurrence and metastasis of nasopharyngeal carcinoma. The prognosis is poor, and vice versa.
3. Expression of invasive markers and results of radiotherapy for nasopharyngeal carcinoma: Precise probability analysis showed that the primary lesion and cervical lymph node shrinkage of nasopharyngeal carcinoma at 70 Gy was higher than that at 50 Gy; the tumor volume shrinkage rate of IMRT group was higher than that of conventional radiotherapy group, the difference was statistically significant (P 0.05); E-cad expression was higher than that of E-cad1 (?), V-cad expression was lower than that of N-cad. There was no significant difference between conventional radiotherapy and intensity modulated radiotherapy (P 0.05). In the low expression group, intensity modulated radiotherapy had a higher rate of tumor regression than conventional radiotherapy (P 0.05). In the high expression group, conventional radiotherapy and intensity modulated radiotherapy had a higher rate of tumor regression than conventional radiotherapy (P 0.05). There was no significant difference in tumor shrinkage rate between the two groups (P 0.05), but in the low expression group of D2-40, the rate of tumor shrinkage in IMRT group was higher than that in conventional radiotherapy group (P 0.05).
Conclusion: EMT exists in nasopharyngeal carcinoma tissues, E-cad protein is low expressed in nasopharyngeal carcinoma, and N-cad protein is high expressed in nasopharyngeal carcinoma, which may lead to the transformation from E-cad to N-cad. Combined detection of E-cad, N-cad, CD34 and D2-40 has certain predictive value for invasion, metastasis and prognosis of nasopharyngeal carcinoma. In early stage nasopharyngeal carcinoma patients, the local control rate of IMRT is similar to that of conventional radiotherapy, suggesting whether proper dose reduction of each dose is beneficial to protect the surrounding normal tissues. Intensity modulated radiation therapy (IMRT) can increase the tumor regression rate in locally advanced nasopharyngeal carcinoma (NPC) patients with low expression of CD34 and D2-40. In patients with different expression of invasive markers, intensity modulated radiation therapy (IMRT) has a higher tumor control rate than conventional radiotherapy, so IMRT may reverse the invasive process.
【学位授予单位】：复旦大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R739.63
【参考文献】
相关期刊论文 前10条
1 王丽辉,刘大渔,陈英杰,候力,王波,毛利民,吕申;乳腺癌淋巴道转移潜能与癌细胞中钙粘素及金属蛋白酶的关系[J];癌症;2002年09期
2 魏军成;吴明富;张永涛;赵良平;卢运萍;马丁;;波形蛋白对前列腺癌细胞侵袭与转移的影响[J];癌症;2008年01期
3 陆身修;钟狂飚;朱利勇;何乐业;;RKIP和E-cadherin在前列腺癌组织中的表达[J];中南大学学报(医学版);2009年09期
4 李骥;王胜资;王纾宜;邹丽芬;阎小军;;鼻咽癌淋巴管和微血管同期检测与预后[J];临床耳鼻咽喉头颈外科杂志;2010年06期
5 江庆萍;王爽;邹桂华;方唯意;姚开泰;;鼻咽癌中上皮间充质改变现象观察[J];热带医学杂志;2008年03期
6 吕艳杰;;上皮—间质转化与肿瘤发生[J];微量元素与健康研究;2007年04期
7 徐娟;唐敏;曹亚;;上皮-间质转化与肿瘤的浸润和转移[J];国际病理科学与临床杂志;2008年06期
8 殷涛;王春友;熊炯p，
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