本文選題：乳腺癌 + 淋巴結(jié)轉(zhuǎn)移　； 參考：《浙江大學(xué)》2017年碩士論文

【摘要】：研究目的乳腺癌是危害女性健康的疾病,發(fā)病率居女性惡性腫瘤之首,且呈快速上升趨勢。作為一種激素相關(guān)性腫瘤,內(nèi)分泌治療是乳腺癌系統(tǒng)治療的一種常規(guī)手段,準(zhǔn)確評估乳腺癌雌激素受體(estrogen receptor,ER)蛋白表達(dá)狀態(tài)對制定臨床治療方案和判斷預(yù)后至關(guān)重要,乳腺癌治療指南明確ER蛋白表達(dá)狀態(tài)檢測,以及孕激素受體(progesterone receptor,PR)蛋白表達(dá)、Ki67指數(shù)和HER-2檢測應(yīng)納入浸潤性乳腺癌的常規(guī)檢查項(xiàng)目。本研究應(yīng)用組織芯片技術(shù)對比研究ER在進(jìn)展期浸潤性乳腺癌原發(fā)灶和同期腋窩淋巴結(jié)轉(zhuǎn)移灶的表達(dá)異同與特點(diǎn),分析乳腺癌淋巴結(jié)轉(zhuǎn)移進(jìn)展過程ER蛋白的均質(zhì)性及穩(wěn)定性,豐富對乳腺癌ER表達(dá)(尤其是轉(zhuǎn)移灶ER表達(dá))狀況的認(rèn)識。研究方法采用回顧性研究方法。收集紹興市人民醫(yī)院病理科2008-2014年伴有同期腋窩淋巴結(jié)轉(zhuǎn)移的原發(fā)女性浸潤性導(dǎo)管癌石蠟存檔標(biāo)本100例,所有病例具有完整臨床資料,手術(shù)術(shù)式為乳腺癌改良根治術(shù),術(shù)前未接受放化療等針對腫瘤的治療措施。每個病例在原發(fā)灶腫瘤標(biāo)本選取標(biāo)記5個典型位點(diǎn),腋窩淋巴結(jié)標(biāo)記所有鏡下可視轉(zhuǎn)移灶位點(diǎn),制備"全信息組織芯片"。采用免疫組織化學(xué)法(IHC)檢測ER蛋白表達(dá),分析其表達(dá)的特點(diǎn)與穩(wěn)定性。根據(jù)ER染色的細(xì)胞數(shù)量和強(qiáng)度進(jìn)行半定量判讀:ER(0):無染色或10%的浸潤性癌細(xì)胞呈現(xiàn)微弱的核染色;(1+):10%-30%的浸潤癌細(xì)胞呈現(xiàn)較弱的核染色;(2+):≥30%的浸潤癌細(xì)胞呈現(xiàn)中等強(qiáng)度的核染色;(3+):≥50%的浸潤癌細(xì)胞呈現(xiàn)較強(qiáng)的核染色。結(jié)果100例浸潤性導(dǎo)管癌患者,原發(fā)灶500個位點(diǎn)中有效位點(diǎn)472個。原發(fā)病灶中只要有一個位點(diǎn)ER+就定義為該患者ER+,本組患者原發(fā)灶ER陽性率53%。ER蛋白表達(dá)情況:47例患者原發(fā)灶所有222個有效位點(diǎn)ER均為陰性表達(dá);41例原發(fā)灶192個有效位點(diǎn)均為ER彌漫一致3+表達(dá);另外12例共58個有效位點(diǎn)ER表達(dá)強(qiáng)度不一致,ER表達(dá)3+,2+,1+,和0的分別為26(44.8%),13(22.4%),7(12.1%)和 12(20.7%)。100例腋窩淋巴結(jié)轉(zhuǎn)移灶有效位點(diǎn)626個,轉(zhuǎn)移淋巴結(jié)中只要一個位點(diǎn)ER+就定位為該患者轉(zhuǎn)移淋巴結(jié)ER+,本組病例轉(zhuǎn)移淋巴結(jié)ER陽性率54%。ER蛋白表達(dá)情況:46例所有249個轉(zhuǎn)移淋巴結(jié)有效位點(diǎn)ER均為陰性表達(dá);33例177個轉(zhuǎn)移淋巴結(jié)有效位點(diǎn)均為ER彌漫一致3+表達(dá);另外21例共200個有效位點(diǎn)ER表達(dá)強(qiáng)度不一致,ER表達(dá)3+,2+,1+,和0的分別為77(38.5%),15(7.5%),9(4.5%),和 99(49.5%)。通過比較100例原發(fā)灶與同期腋窩淋巴結(jié)轉(zhuǎn)移灶ER蛋白表達(dá)情況,在原發(fā)灶所有位點(diǎn)ER3+表達(dá)的41例中,234(86.0%)個淋巴結(jié)轉(zhuǎn)移灶ER3+表達(dá),ER表達(dá)2+,1+,和0轉(zhuǎn)移灶位點(diǎn)數(shù)分別為10(3.7%),4(1.5%)和24(8.8%)。按病例分析,39例(95.1%)相應(yīng)轉(zhuǎn)移淋巴結(jié)中見ER陽性表達(dá),而28例所有淋巴結(jié)轉(zhuǎn)移灶(168)均為3+表達(dá);剩余2例總共3個淋巴結(jié)均陰性表達(dá)。原發(fā)灶所有位點(diǎn)ER均為陰性表達(dá)47例中,298(96.1%)個淋巴結(jié)轉(zhuǎn)移灶ER陰性表達(dá),ER表達(dá)1+,2+和3+的轉(zhuǎn)移灶位點(diǎn)數(shù)分別為3(1%),3(1%)和6(1.9%)。按病例分析,40例所有淋巴結(jié)轉(zhuǎn)移灶位點(diǎn)(224)均為陰性表達(dá);1例所有4個淋巴結(jié)轉(zhuǎn)移灶ER表達(dá)均為彌漫一致3+;另外6例共82個轉(zhuǎn)移灶有效位點(diǎn)中,74(90.2%)個位點(diǎn)ER均為陰性表達(dá),ER表達(dá)1+,2+和3+的位點(diǎn)數(shù)分別為3(3.7%),3(3.7%)和 2(2.4%)。在原發(fā)灶位點(diǎn)ER表達(dá)不一致的12例中,總共獲得44個腋窩淋巴結(jié)轉(zhuǎn)移灶位點(diǎn)。其中4例轉(zhuǎn)移淋巴結(jié)ER陰性,4例轉(zhuǎn)移淋巴結(jié)ER彌漫一致3+表達(dá),另外4例的17枚轉(zhuǎn)移淋巴結(jié)ER表達(dá)3+,2+,1+,0的位點(diǎn)分別為9(52.9%),2(11.8%),2(11.8%)和 4(23.5%)。原發(fā)灶和淋巴結(jié)轉(zhuǎn)移灶總的一致率87%。分層分析,在原發(fā)灶有ER陽性表達(dá)的53例中,47例相應(yīng)淋巴結(jié)轉(zhuǎn)移灶呈ER陽性表達(dá),剩余6例的所有轉(zhuǎn)移灶ER表達(dá)陰性,原發(fā)灶和轉(zhuǎn)移灶ER陽性表達(dá)的一致率為88.7%,其中原發(fā)灶ER全部3+陽性表達(dá)的41例中,39例相應(yīng)淋巴結(jié)轉(zhuǎn)移灶ER陽性表達(dá),一致率為95.1%;原發(fā)灶所有位點(diǎn)ER全陰的47例中,40例相應(yīng)淋巴結(jié)轉(zhuǎn)移灶均陰性表達(dá),7例淋巴結(jié)轉(zhuǎn)移灶ER陽性表達(dá),原發(fā)灶和轉(zhuǎn)移灶ER陰性表達(dá)的一致率為85.1%;原發(fā)灶位點(diǎn)ER表達(dá)但強(qiáng)度不一致(3+,2+,1 +)的12例中,8例見ER陽性轉(zhuǎn)移淋巴結(jié),一致率為66.7%。結(jié)論1、進(jìn)展期乳腺浸潤性導(dǎo)管癌ER蛋白表達(dá)在腫瘤原發(fā)灶和同期腋窩淋巴結(jié)轉(zhuǎn)移灶之間一致性較高,其中原發(fā)灶ER全陰或者彌漫一致3+表達(dá)的病例,淋巴結(jié)與原發(fā)灶表達(dá)的一致性更高。2、應(yīng)用組織芯片技術(shù)對腫瘤原發(fā)灶和同期腋窩淋巴結(jié)轉(zhuǎn)移灶進(jìn)行多點(diǎn)取樣,更能全面反映腫瘤的ER蛋白表達(dá)狀態(tài)。3、在組織芯片標(biāo)本實(shí)施ER蛋白免疫組化檢測表達(dá)模式呈現(xiàn)或3+或陰性表達(dá)。4、本組患者ER陽性率略低,可能與患者均有淋巴結(jié)轉(zhuǎn)移有關(guān)。
[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.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R737.9

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