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NY-ESO-1与MAGE-As家族在人乳腺癌组织中的表达及与肿瘤浸润性T细胞的相关性研究

发布时间:2018-09-13 15:03
【摘要】:目的:探讨人黑色素瘤抗原(melanoma antigen gene-As,MAGE-As)、食管鳞状细胞癌抗原(New York-esop Hageal-1,NY-ESO-1)在乳腺癌中的表达情况及意义;同时探讨在四种分子亚型的乳腺癌中NY-ESO-1、MAGE-As的表达差异及与细胞毒性T淋巴细胞(cytotoxic T lymphocytes,CTL)的相关性。方法:1.收集从2014年1月—2016年1月至本院住院且最终在组织病理学上确诊是浸润性乳腺癌的组织标本150例,同时在已选定的乳腺癌组织标本中用随机数法选择50例距癌组织5cm外病理确诊为正常乳腺组织的标本。2.整理归纳入组样本对应病人的一般信息资料如:患者的年龄、肿瘤的病理大小、淋巴结状态、pTNM分期、脉管浸润癌栓、WHO分级等。3.根据2013年St.Gellen对乳腺癌的分型标准,将入选样本分为Luminal A、B型,HER-2亚型及三阴型。4.利用Envision法检测选取的标本组织中NY-ESO-1、MAGE-As的表达及癌组织中CTL的浸润情况。5.对不同分子分型的乳腺癌NY-ESO-1、MAGE-As的表达进行分析并与CTL的浸润情况进行相关性分析。结果:1.NY-ESO-1、MAGE-As在正常乳腺组织中不表达,NY-ESO-1在乳腺癌中的表达率为8.7%(13/150),NY-ESO-1在两种不同组织中表达具有差异性(χ2=3.32 P=0.021);MAGE-As在乳腺癌中的阳性率为38.7%(58/150),与正常组织中的阳性率相较,MAGE-As在乳腺癌组织中表达较高(χ2=27.23 P=0.000);NY-ESO-1、MAGE-As在乳腺癌组织中的表达无显著相关(r=0.047 P=0.565)。2.NY-ESO-1在乳腺癌中的表达仅与组织学分级有关(χ2=16.66P=0.000),与年龄(χ2=0.025 P=0.426)、肿瘤大小(χ2=1.353 P=0.245)、淋巴结转移(χ2=0.604 P=0.739)、脉管瘤栓(χ2=1.001 P=0.159)、病理分期(χ2=0.027 P=0.870)无显著相关(P0.05);MAGR-As表达与脉管瘤栓(χ2=0.695 P=0.278)、组织学分级(χ2=4.243 P=0.120)、年龄(χ2=2.1 P=0.102)、肿瘤大小(χ2=1.875 P=0.171)、淋巴结转移(χ2=1.060 P=0.589)、病理分期(χ2=6.857 P=0.077)、ER状态(χ2=2.513 P=0.131)、PR状态(χ2=1.949 P=0.163)均无相关性(P0.05)。3.NY-ESO-1的表达与乳腺癌的不同分子分型有关(χ2=42.389P=0.000),且仅表达在三阴型乳腺癌中(P0.05);MAGE-As在不同分子分型中表达具有差异性(χ2=7.925 P=0.048);CTL在乳腺癌组织中的浸润程度在四种分子亚型中未表现出差异性(χ2=8.990P=0.438);4.NY-ESO-1的表达与乳腺癌中CTL不同浸润程度有关(χ2=8.917P=0.03),且在三阴型乳腺癌中NY-ESO-1的表达与较高水平的CTL具有显著的相关性(χ2=5.593 P=0.018);MAGE-As的表达与乳腺癌中CTL不同浸润程度无关(χ2=1.138 P=0.286),但MAGE-As在HER-2亚型乳腺癌中与CTL不同浸润程度的有关(χ2=5.818 P=0.016),与Luminal A型乳腺癌(χ2=1.855 P=0.173)、Luminal B型(χ2=1.678P=0.195)、三阴型乳腺癌(χ2=1.779 P=0.180)中CTL浸润程度均无关(P0.05)。结论:1.NY-ESO-1、MAGE-As抗原蛋白在乳腺癌中高表达,是乳腺癌的相关性抗原。2、NY-ESO-1仅在不同WHO分级中表现出差异,与年龄、肿瘤大小、淋巴结状态、脉管瘤栓、pTNM分期无关;MAGR-As表达与WHO分级、年龄、肿瘤大小、淋巴结状态、pTNM分期、脉管瘤栓均无关。3、NY-ESO-1在TNBC中特异性表达,并且其表达与CTL的浸润程度成正相关;MAGE-As表达与乳腺癌的不同分子亚型有关,并且MAGE-As仅在HER-2亚型乳腺癌中与CTL浸润程度呈负相关。
[Abstract]:Objective: To investigate the expression and significance of human melanoma antigen gene-As (MAGE-As) and esophageal squamous cell carcinoma antigen (NY-ESO-1) in breast cancer, and to explore the difference between the expression of NY-ESO-1 and MAGE-As and cytotoxic T lymphocyte (cytotoxic T lymphocyte) in four molecular subtypes of breast cancer. Methods: 1. 150 specimens of invasive breast cancer were collected from January 2014 to January 2016, and 50 specimens of normal breast tissue were selected by random number method. 2. According to the classification standard of breast cancer by St. Gellen in 2013, the selected samples were divided into Luminal A, B, HER-2 subtypes and three negative subtypes. The expression of NY-ESO-1, MAGE-As and the infiltration of CTL in breast cancer tissues were studied. 5. The expression of NY-ESO-1 and MAGE-As in different molecular types of breast cancer was analyzed and correlated with the infiltration of CTL. Results: 1. NY-ESO-1, MAGE-As were not expressed in normal breast tissues, and the expression of NY-ESO-1 in breast cancer was 8.7% (13/15). The positive rate of MAGE-As in breast cancer was 38.7% (58/150), which was higher than that in normal tissues (_2 = 27.23 P = 0.000); the expression of NY-ESO-1 and MAGE-As in breast cancer was not significantly correlated (r = 0.047 P = 0.56 P = 0.000). The expression of NY-ESO-1 in breast cancer was only correlated with histological grade (962 = 16.66P = 0.000), age (962 = 0.025 P = 0.426), tumor size (\962 = 1.353 P = 0.245), lymph node metasta (\962 = 0.604 P = 0.604 P = 0.739), angioma embolism (\962 = 1.001 P = 1.001 P = 0.159), pathologstage (\\962 = 0.027 = 0.027 = 0.877 = 0.87P = 0.876), tumor size (962 = 1.35 = 1.35 = 1.353 P = 1.35 = 0.35 = 0.Expression of-As and Vascular Tumor Thrombus (_2=0) 695 P = 0.278, histological grade (962 = 4.243 P = 0.077), age (962 = 2.1 P = 0.120), age (962 = 2.1 P = 0.102), tumor size (962 = 1.875 P = 0.171), lymph node metasta (962 = 1.060 P = 0.0 P = 0.589), pathologstag (962 = 6.857 P = 0.77 = 0.077), ER status (\\\\\\\\\\2 = 2.3 P = 0.131 = 0.1), PRstate (\\\\\Correlation (P 0.05). 3. Expression of NY-ESO-1 and Different Molecular Fractions of Breast Cancer The expression of MAGE-As was different in different molecular types (2 = 7.925 P = 0.048); the infiltration degree of CTL in breast cancer tissue showed no difference among the four molecular subtypes (2 = 8.990 P = 0.438); the expression of 4.NY-ESO-1 was different from that of CTL in breast cancer tissue. The expression of NY-ESO-1 in triple-negative breast cancer was significantly correlated with the higher level of CTL (_2 = 5.593 P = 0.018); the expression of MAGE-As was not correlated with the different degree of invasion of CTL in breast cancer (_2 = 1.138 P = 0.286), but MAGE-As was correlated with the different degree of invasion of CTL in HER-2 subtype breast cancer (_2 = 5.818 P = 0.018). Conclusion: 1. NY-ESO-1, MAGE-As antigen protein is highly expressed in breast cancer, and it is associated with breast cancer antigen. 2. NY-ESO-1 is only different in different WHO grades. The expression of MAGR-As was not correlated with WHO grade, age, tumor size, lymph node status, pTNM stage, and vascular thrombus. 3. The expression of NY-ESO-1 in TNBC was positively correlated with the infiltration of CTL. The expression of MAGE-As was positively correlated with different molecular subtypes of breast cancer. Guan, and MAGE-As only negatively correlated with CTL infiltration in HER-2 subtype breast cancer.
【学位授予单位】:西南医科大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R737.9

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