进展期乳腺浸润性导管癌ER蛋白表达的稳定性分析

发布时间：2018-06-04 00:16

本文选题：乳腺癌 + 淋巴结转移　；参考：《浙江大学》2017年硕士论文

【摘要】：研究目的乳腺癌是危害女性健康的疾病,发病率居女性恶性肿瘤之首,且呈快速上升趋势。作为一种激素相关性肿瘤,内分泌治疗是乳腺癌系统治疗的一种常规手段,准确评估乳腺癌雌激素受体(estrogen receptor,ER)蛋白表达状态对制定临床治疗方案和判断预后至关重要,乳腺癌治疗指南明确ER蛋白表达状态检测,以及孕激素受体(progesterone receptor,PR)蛋白表达、Ki67指数和HER-2检测应纳入浸润性乳腺癌的常规检查项目。本研究应用组织芯片技术对比研究ER在进展期浸润性乳腺癌原发灶和同期腋窝淋巴结转移灶的表达异同与特点,分析乳腺癌淋巴结转移进展过程ER蛋白的均质性及稳定性,丰富对乳腺癌ER表达(尤其是转移灶ER表达)状况的认识。研究方法采用回顾性研究方法。收集绍兴市人民医院病理科2008-2014年伴有同期腋窝淋巴结转移的原发女性浸润性导管癌石蜡存档标本100例,所有病例具有完整临床资料,手术术式为乳腺癌改良根治术,术前未接受放化疗等针对肿瘤的治疗措施。每个病例在原发灶肿瘤标本选取标记5个典型位点,腋窝淋巴结标记所有镜下可视转移灶位点,制备"全信息组织芯片"。采用免疫组织化学法(IHC)检测ER蛋白表达,分析其表达的特点与稳定性。根据ER染色的细胞数量和强度进行半定量判读:ER(0):无染色或10%的浸润性癌细胞呈现微弱的核染色;(1+):10%-30%的浸润癌细胞呈现较弱的核染色;(2+):≥30%的浸润癌细胞呈现中等强度的核染色;(3+):≥50%的浸润癌细胞呈现较强的核染色。结果100例浸润性导管癌患者,原发灶500个位点中有效位点472个。原发病灶中只要有一个位点ER+就定义为该患者ER+,本组患者原发灶ER阳性率53%。ER蛋白表达情况:47例患者原发灶所有222个有效位点ER均为阴性表达;41例原发灶192个有效位点均为ER弥漫一致3+表达;另外12例共58个有效位点ER表达强度不一致,ER表达3+,2+,1+,和0的分别为26(44.8%),13(22.4%),7(12.1%)和 12(20.7%)。100例腋窝淋巴结转移灶有效位点626个,转移淋巴结中只要一个位点ER+就定位为该患者转移淋巴结ER+,本组病例转移淋巴结ER阳性率54%。ER蛋白表达情况:46例所有249个转移淋巴结有效位点ER均为阴性表达;33例177个转移淋巴结有效位点均为ER弥漫一致3+表达;另外21例共200个有效位点ER表达强度不一致,ER表达3+,2+,1+,和0的分别为77(38.5%),15(7.5%),9(4.5%),和 99(49.5%)。通过比较100例原发灶与同期腋窝淋巴结转移灶ER蛋白表达情况,在原发灶所有位点ER3+表达的41例中,234(86.0%)个淋巴结转移灶ER3+表达,ER表达2+,1+,和0转移灶位点数分别为10(3.7%),4(1.5%)和24(8.8%)。按病例分析,39例(95.1%)相应转移淋巴结中见ER阳性表达,而28例所有淋巴结转移灶(168)均为3+表达;剩余2例总共3个淋巴结均阴性表达。原发灶所有位点ER均为阴性表达47例中,298(96.1%)个淋巴结转移灶ER阴性表达,ER表达1+,2+和3+的转移灶位点数分别为3(1%),3(1%)和6(1.9%)。按病例分析,40例所有淋巴结转移灶位点(224)均为阴性表达;1例所有4个淋巴结转移灶ER表达均为弥漫一致3+;另外6例共82个转移灶有效位点中,74(90.2%)个位点ER均为阴性表达,ER表达1+,2+和3+的位点数分别为3(3.7%),3(3.7%)和 2(2.4%)。在原发灶位点ER表达不一致的12例中,总共获得44个腋窝淋巴结转移灶位点。其中4例转移淋巴结ER阴性,4例转移淋巴结ER弥漫一致3+表达,另外4例的17枚转移淋巴结ER表达3+,2+,1+,0的位点分别为9(52.9%),2(11.8%),2(11.8%)和 4(23.5%)。原发灶和淋巴结转移灶总的一致率87%。分层分析,在原发灶有ER阳性表达的53例中,47例相应淋巴结转移灶呈ER阳性表达,剩余6例的所有转移灶ER表达阴性,原发灶和转移灶ER阳性表达的一致率为88.7%,其中原发灶ER全部3+阳性表达的41例中,39例相应淋巴结转移灶ER阳性表达,一致率为95.1%;原发灶所有位点ER全阴的47例中,40例相应淋巴结转移灶均阴性表达,7例淋巴结转移灶ER阳性表达,原发灶和转移灶ER阴性表达的一致率为85.1%;原发灶位点ER表达但强度不一致(3+,2+,1 +)的12例中,8例见ER阳性转移淋巴结,一致率为66.7%。结论1、进展期乳腺浸润性导管癌ER蛋白表达在肿瘤原发灶和同期腋窝淋巴结转移灶之间一致性较高,其中原发灶ER全阴或者弥漫一致3+表达的病例,淋巴结与原发灶表达的一致性更高。2、应用组织芯片技术对肿瘤原发灶和同期腋窝淋巴结转移灶进行多点取样,更能全面反映肿瘤的ER蛋白表达状态。3、在组织芯片标本实施ER蛋白免疫组化检测表达模式呈现或3+或阴性表达。4、本组患者ER阳性率略低,可能与患者均有淋巴结转移有关。
[Abstract]:Research objective breast cancer is a disease which endangering women's health. The incidence of the disease is the first of the female malignant tumor, and it is rising rapidly. As a hormone related tumor, endocrine therapy is a routine method for the treatment of breast cancer system. It is an accurate assessment of the expression of estrogen receptor, ER protein in breast cancer. The bed treatment scheme and prognosis are very important. The breast cancer treatment guide is to determine the expression of ER protein and the expression of progesterone receptor (progesterone receptor, PR) protein. The Ki67 index and HER-2 detection should be included in the routine examination of invasive breast cancer. This study should use tissue chip technique to compare the infiltration of ER in progressing stage. The differences and characteristics of the expression of the primary breast cancer and the axillary lymph node metastases in the same period, analyze the homogeneity and stability of ER protein in the progression of lymph node metastasis of breast cancer, and enrich the understanding of the ER expression of breast cancer (especially the ER expression in the metastatic foci). The retrospective study method is used to collect the pathology department of Shaoxing People's Hospital 20. 100 paraffin specimens of primary female invasive ductal carcinoma with axillary lymph node metastases were found in 100 cases. All cases had complete clinical data. The surgical operation was modified radical mastectomy, and preoperative radiotherapy and chemotherapy were not accepted. 5 typical loci were selected in the primary tumor specimens in each case. The axillary lymph nodes were labeled with all visual transfer sites under the microscope to prepare a "full information tissue chip". The expression of ER protein was detected by immunohistochemistry (IHC), and the characteristics and stability of the expression were analyzed. According to the number and intensity of ER stained cells, ER (0): no staining or 10% infiltrative cancer cells showed weak nuclear staining. Color; (1+): the infiltrating cancer cells of 10%-30% showed weak nuclear staining; (2+): more than 30% of infiltrating cancer cells showed moderate intensity of nuclear staining; (3+): more than 50% of infiltrating cancer cells showed strong nuclear staining. Results 100 cases of invasive ductal carcinoma, 472 of the 500 sites of primary focus. Only one site in the primary focus was ER+. The expression of ER positive rate 53%.ER protein in the primary focus of this group was ER+: all 222 effective loci of the primary foci in 47 cases were negative, and 192 effective sites in 41 primary foci were ER diffuse 3+ expression; the other 12 cases had 58 effective sites, ER expression intensity was not consistent, ER expression 3+, 2+, 1+, and 0 were 26 (44.8%) respectively. 13 (22.4%), 7 (12.1%) and 12 (20.7%).100 cases of axillary lymph node metastases were effective in 626. Only one loci ER+ in the metastatic lymph node was located as the metastatic lymph node ER+ in the patient. The ER positive rate of 54%.ER protein expression in the lymph node metastasis of this group: 249 of the 249 metastatic lymph nodes in 46 cases were negative, and 33 cases 177. The effective loci of the metastatic lymph nodes were all ER diffuse 3+ expression, and the other 21 cases with 200 effective sites were dissimilar in ER expression, ER expressed 3+, 2+, 1+, and 0, respectively, 77 (38.5%), 15 (7.5%), 9 (4.5%), and 99 (49.5%). By comparing the expression of ER protein in the primary and the same phase of the axillary lymph node metastasis, ER3+ at all sites in the primary foci. Of the 41 cases expressed, 234 (86%) lymph node metastases were expressed in ER3+, ER expression 2+, 1+, and 0 metastatic foci were 10 (3.7%), 4 (1.5%) and 24 (8.8%). According to case analysis, ER positive expression was found in the metastatic lymph nodes in 39 cases (95.1%), and all lymph nodes in all lymph nodes were expressed as 3+, and the remaining lymph nodes were negative expression in the remaining cases. In 47 cases with negative expression of ER, 298 (96.1%) lymph node metastasis ER negative expression, ER expression 1+, 2+ and 3+ metastasis location points were 3 (1%), 3 (1%) and 6 (1.9%). 40 cases of lymph node metastasis loci (224) were negative expression, ER expression in all 4 lymph node metastases of 1 cases were diffuse one. 3+; in the other 6 effective loci of 82 metastatic foci, 74 (90.2%) loci were negative, ER expressed 1+, 2+ and 3+ were 3 (3.7%), 3 (3.7%) and 2 (2.4%). In 12 cases of primary focal site ER, a total of 44 axillary lymph node metastasis loci were obtained. Among them, metastatic lymph nodes were ER negative and metastasis lymph nodes were metastatic. ER expressed 3+, and 17 metastatic lymph nodes in the other 4 cases expressed 3+, 2+, 1+, and 0, respectively, 9 (52.9%), 2 (11.8%), 2 (11.8%) and 4 (23.5%). The total consistency of primary and lymph node metastases was 87%. stratified analysis. Among the primary foci of ER positive expression, the corresponding lymph node metastases were expressed in ER positive and remaining in the remaining cases. The expression of ER was negative in all metastatic foci, and the positive rate of positive expression of ER in primary and metastatic foci was 88.7%. Of the 41 cases with positive ER 3+ positive expression in the primary foci, 39 cases of corresponding lymph node metastasis were ER positive, the rate of agreement was 95.1%. In 47 cases of ER full Yin at all sites of primary foci, 40 cases of corresponding lymph node metastases were negative and 7 lymph nodes were transferred. The positive expression of ER was 85.1%, and the negative expression of ER in primary and metastatic foci was 85.1%. In 12 cases of primary foci, but the intensity was not consistent (3+, 2+, 1 +), 8 cases had ER positive metastatic lymph nodes, the coincidence rate was 66.7%. conclusion 1. The expression of ER egg white in invasive ductal carcinoma of the mammary gland was in the primary tumor and axillary lymph node metastases at the same time. The consistency between the primary foci and the same 3+ expression in the primary ER was higher. The consistency of the lymph nodes with the primary foci was higher.2. The tissue chip technology was used to sample the primary tumor and the axillary lymph node metastases at the same time. The expression of the ER protein in the tumor was fully reflected, and the expression of the tumor was.3, and ER was carried out in the tissue chip specimen. Immunohistochemical staining showed that the expression pattern of 3+ was negative or.4 negative. The positive rate of ER in this group was slightly lower, which might be related to lymph node metastasis.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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