本文選題：結(jié)直腸腺癌　切入點：HER2　出處：《河北醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的:通過檢測結(jié)直腸腺癌、腺瘤以及癌旁無瘤粘膜組織中人類表皮生長因子受體2(human epidermalgrowth factor receptor-2,HER2)、表皮生長因子受體(epidermal growth factor receptor,EGFR)、S100A14蛋白的表達變化,探討三種蛋白表達的表達變化與結(jié)直腸腺癌發(fā)生的關(guān)系;分析結(jié)直腸腺癌中HER2、EGFR、S100A14的表達與臨床病理指標的相關(guān)性,探討三種蛋白在結(jié)直腸腺癌發(fā)展中的作用。旨在探討在結(jié)直腸腺癌發(fā)生發(fā)展過程中HER2、EGFR、S100A14的作用及可能機制。方法:選取2012年6月至2013年8月在唐山市工人醫(yī)院行結(jié)直腸腺癌手術(shù)切除的標本進行研究。其中腺癌120例,同時選取對應(yīng)癌旁無瘤粘膜組織(距離大于2cm)84例。另外選取手術(shù)切除的結(jié)直腸腺瘤84例。用免疫組化法(SP法)檢測HER2、EGFR、S100A14在不同組織中的表達。用SPSS17.0統(tǒng)計學(xué)軟件對數(shù)據(jù)作出統(tǒng)計學(xué)分析。結(jié)果:1 HER2蛋白在結(jié)直腸腺癌、腺瘤以及癌旁無瘤粘膜組織中的陽性率分別為70.00%、14.28%、11.90%,結(jié)直腸腺癌組織中HER2蛋白的表達陽性率遠遠高于腺瘤和癌旁無瘤粘膜組織中HER2蛋白的陽性率,其差別均具有統(tǒng)計學(xué)意義(分別為X2=61.564,P=0.000;X2=67.120,P=0.000),腺瘤組織和癌旁無瘤粘膜組織之間陽性率的差異無統(tǒng)計學(xué)意義(X2=0.209,P=0.647)。2在結(jié)直腸腺癌組織中,HER2蛋白在中、高分化組的表達陽性率為57.57%,在低分化組表達陽性率為85.18%,兩組差異具有統(tǒng)計學(xué)意義(X2=10.781,P=0.001);伴有淋巴結(jié)轉(zhuǎn)移的結(jié)直腸腺癌組織中,HER2蛋白的表達陽性率為88.89%,而無淋巴結(jié)轉(zhuǎn)移的結(jié)直腸腺癌組織中,HER2蛋白的表達陽性率為54.54%,其差別有統(tǒng)計學(xué)意義(X2=16.681,P=0.000);在腫瘤未浸潤至漿膜和浸潤至(或超過)漿膜的結(jié)直腸腺癌組織中的HER2蛋白的表達分別為59.01%和81.35%,兩組差別有統(tǒng)計學(xué)意義(X2=7.127,P=0.008);在TNM分期Ⅰ+Ⅱ期和Ⅲ+Ⅳ期中的表達陽性率分別為60.31%和80.70%,兩組差別有統(tǒng)計學(xué)意義(X2=5.921,P=0.015);而HER2蛋白在不同年齡、不同性別、不同腫瘤部位的結(jié)直腸腺癌比較中,其表達差別無統(tǒng)計學(xué)意義(P0.05)。3 EGFR蛋白在結(jié)直腸腺癌、腺瘤以及癌旁無瘤粘膜組織中的表達陽性率分別為65.83%、57.14%、35.71%,結(jié)直腸腺癌組織中EGFR蛋白的表達陽性率遠遠高于癌旁無瘤粘膜組織中EGFR蛋白的陽性率,其差別具有統(tǒng)計學(xué)意義(X2=18.015,P=0.000),腺瘤組織中陽性率高于癌旁無瘤粘膜組織中的陽性率,其差別有統(tǒng)計學(xué)意義(X2=7.754,P=0.005),腺癌組織和腺瘤組織之間陽性率的差異無統(tǒng)計學(xué)意義(X2=1.588,P=0.208)。4結(jié)直腸腺癌組織中,EGFR蛋白在中、高分化組的表達陽性率為51.56%,低分化組的表達陽性率為82.14%,兩組差異具有統(tǒng)計學(xué)意義(X2=12.417,P=0.000);伴有淋巴結(jié)轉(zhuǎn)移的腺癌組織中,EGFR蛋白的陽性率(87.03%)明顯高于無淋巴結(jié)轉(zhuǎn)移的腺癌組織中EGFR蛋白的陽性率(51.51%),其差別有統(tǒng)計學(xué)意義(X2=17.083,P=0.000);在腫瘤未浸潤至漿膜和浸潤至(或超過)漿膜的結(jié)直腸腺癌組織中的EGFR蛋白的陽性率分別為50.81%和81.35%,兩組差別有統(tǒng)計學(xué)意義(X2=12.433,P=0.000);在TNM分期Ⅰ+Ⅱ期和Ⅲ+Ⅳ期中的陽性率分別為57.14%和75.43%,兩組差別有統(tǒng)計學(xué)意義(X2=4.453,P=0.035);而EGFR蛋白的表達在不同年齡、不同性別、不同腫瘤部位的腺癌中,其表達差別無統(tǒng)計學(xué)意義(P0.05)。5 S100A14蛋白結(jié)直腸腺癌、腺瘤以及癌旁無瘤粘膜組織中的陽性率分別是66.67%、66.67%、45.24%,結(jié)直腸腺癌組織中S100A14蛋白的表達陽性率遠遠高于癌旁無瘤粘膜組織中S100A14蛋白的陽性率,其差別具有統(tǒng)計學(xué)意義(X2=9.305,P=0.002),腺瘤組織中陽性率高于癌旁無瘤粘膜組織中的陽性率,其差別有統(tǒng)計學(xué)意義(X2=7.825,P=0.005),腺癌組織和腺瘤組織之間陽性率的差異無統(tǒng)計學(xué)意義(X2=0.000,P=1.000)。6在結(jié)直腸腺癌組織中S100A14蛋白的中、高分化組的陽性率為50%,低分化組的陽性率為85.17%,兩組差別具有統(tǒng)計學(xué)意義(X2=17.143,P=0.000);伴有淋巴結(jié)轉(zhuǎn)移的結(jié)直腸腺癌組織中,S100A14蛋白的陽性率為81.48%,而無發(fā)生淋巴結(jié)轉(zhuǎn)移的結(jié)直腸腺癌組織中,S100A14蛋白的陽性率為54.54%,其差別有統(tǒng)計學(xué)意義(X2=9.796,P=0.002);在腫瘤未浸潤至漿膜和浸潤至(或超過)漿膜的結(jié)直腸腺癌組織中的S100A14蛋白的陽性率分別為54.09%和79.66%,兩組差別有統(tǒng)計學(xué)意義(X2=8.819,P=0.003);在TNM分期Ⅰ+Ⅱ期和Ⅲ+Ⅳ期中的陽性率分別為50.79%和84.21%,兩組差別有統(tǒng)計學(xué)意義(X2=15.038,P=0.000);S100A14蛋白的表達在不同年齡、不同性別、不同腫瘤部位的腺癌中,其表達差別無統(tǒng)計學(xué)意義(P0.05)。7經(jīng)SPSS17.0軟件的spearman檢驗分析顯示,結(jié)直腸腺癌組織中的HER2和EGFR呈正相關(guān)(r=0.28,P=0.002),HER2和S100A14呈正相關(guān)(r=0.309,P=0.001),EGFR和S100A14呈正相關(guān)(r=0.564,P=0.000)。結(jié)論:1 HER2、EGFR、S100A14蛋白在結(jié)直腸腺癌中過度表達,明顯高于無瘤粘膜,表明三者可能參與癌變過程。2 HER2、EGFR、S100A14蛋白的高表達與分化差、淋巴結(jié)轉(zhuǎn)移、浸潤深及TNMⅢ+Ⅳ相關(guān),表明HER2、EGFR、S100A14可能與結(jié)直腸腺癌的惡性生物學(xué)行為有關(guān)。3在結(jié)直腸腺癌中HER2、EGFR、S100A14蛋白的表達呈兩兩相關(guān),表明三者在結(jié)直腸癌發(fā)生發(fā)展中的作用通路可能存在交互作用。
[Abstract]:Objective: through the detection of colorectal adenocarcinoma, adenoma and adjacent non tumor tissues of human epidermal growth factor receptor 2 (human epidermalgrowth factor receptor-2, HER2), epidermal growth factor receptor (epidermal growth factor receptor, EGFR), S100A14 protein expression, to explore the relationship between the expression of three kinds of protein expression and colorectal adenocarcinoma cancer; analysis of HER2, EGFR in colorectal adenocarcinoma and the correlation between S100A14 expression and clinicopathological parameters, to investigate the effect of three kinds of protein in colorectal adenocarcinoma development. To investigate the direct HER2, in the process of the development of intestinal adenocarcinoma in EGFR, the role of S100A14 and its possible mechanism. Methods: from June 2012 to August 2013 study in Tangshan City workers' hospital for colorectal cancer resection specimens including 120 cases of adenocarcinoma, and select the corresponding adjacent non tumor tissues (distance greater than 2cm) in 84 cases. In addition to select surgical resection in 84 cases of colorectal adenoma. Using immunohistochemical method (SP method) to detect HER2, EGFR, S100A14 expression in different tissues. Statistical analysis of data by SPSS17.0 statistical software. Results: 1 HER2 protein in colorectal adenocarcinoma, adenoma and adjacent non tumor tissues. The positive rate of were 70%, 14.28%, 11.90%, the positive expression rate of HER2 protein in colorectal adenocarcinoma tissues is much higher than the positive rate of adenomas and carcinomas without HER2 protein in tumor tissues, the difference was statistically significant (X2=61.564, P=0.000; X2=67.120, P=0.000), no statistically significant difference between adenomas and carcinomas without between the positive rate of tumor tissue (X2=0.209, P=0.647).2 in colorectal cancer tissues, HER2 protein positive expression rate in high differentiation group was 57.57%, in the low differentiation group positive expression rate was 85.18%, with the difference between the two groups Statistical significance (X2=10.781, P=0.001); lymph node metastasis in colorectal adenocarcinoma tissues, the positive expression rate of HER2 protein was 88.89%, and no lymph node metastasis in colorectal adenocarcinoma tissues, the positive expression rate of HER2 protein was 54.54%, the difference was statistically significant (X2=16.681, P=0.000); in without tumor infiltration to serosa and infiltrating into the serosa (or more than) expression in colorectal adenocarcinoma tissues of HER2 protein were 59.01% and 81.35%, there was significant difference between the two groups (X2=7.127, P=0.008); the positive expression rate of TNM in stage I + II and III + IV in 60.31% and 80.70% respectively, there was statistical significant difference between the two groups (X2=5.921, P=0.015); and HER2 protein in different age, different gender, different parts of the tumor in colorectal adenocarcinoma, the expression had no significant difference (P0.05) of.3 EGFR protein in colorectal adenocarcinoma, adenoma and adjacent non tumor The positive expression rate of mucosa were 65.83%, 57.14%, 35.71%, the positive expression rate of EGFR protein in colorectal adenocarcinoma tissues is much higher than the positive rate of EGFR protein in tumor adjacent non cancer tissues, the difference was statistically significant (X2=18.015, P=0.000), the positive rate of adenoma tissues than adjacent non tumor positive rate mucosal tissues, the difference was statistically significant (X2=7.754, P=0.005), there was no significant difference between adenocarcinoma and adenoma tissue positive rate (X2=1.588, P=0.208).4 in colorectal adenocarcinoma tissues, EGFR protein positive expression rate in high differentiation group was 51.56%, the positive expression rate of low differentiation group 82.14%, with significant difference between two groups (X2=12.417, P=0.000); lymph node metastasis of adenocarcinoma, the positive rate of EGFR protein (87.03%) was significantly higher than the positive rate of EGFR protein and lymph node metastasis in adenocarcinoma (5 1.51%), the difference was statistically significant (X2=17.083, P=0.000); in tumor infiltrating serosa and invasion to serosa (or more than) the positive rate of the colorectal adenocarcinoma tissues of EGFR protein were 50.81% and 81.35%, there was significant difference between the two groups (X2=12.433, P= 0); the positive rate in TNM stage I + II and III + IV in 57.14% and 75.43% respectively, there was significant difference between the two groups (X2=4.453, P=0.035); and the expression of EGFR protein in different age, different gender, different parts of the tumor in adenocarcinoma, the expression of the difference was no statistical significance (P0.05) of.5 S100A14 protein in colorectal adenocarcinoma, adenoma and adjacent non tumor tissues and the positive rate were 66.67%, 66.67%, 45.24%, the positive expression rate of S100A14 protein in colorectal adenocarcinoma tissues is much higher than the positive rate of S100A14 protein in tumor adjacent non cancer tissues, the difference was statistically significant (X2 =9.305, P=0.002), the positive rate of adenoma tissues than adjacent non tumor tissues the positive rate, the difference was statistically significant (X2=7.825, P=0.005), there was no significant difference between adenocarcinoma and adenoma tissue positive rate (X2=0.000, P=1.000).6 S100A14 in colorectal adenocarcinoma protein. The positive rate of high differentiation group was 50%, the positive rate of low differentiation group was 85.17%, statistically significant difference between the two groups (X2=17.143, P=0.000); lymph node metastasis in colorectal adenocarcinoma tissues, the positive rate of S100A14 protein was 81.48%, and no lymph node metastasis in colorectal adenocarcinoma tissues, the positive rate of the S100A14 protein was 54.54%, the difference was statistically significant (X2=9.796, P=0.002); in tumor infiltrating serosa and invasion to serosa (or more than) the positive rate of the colorectal adenocarcinoma tissues of S100A14 protein were 54.09% and 79.66%, the two groups The difference was statistically significant (X2=8.819, P=0.003); the positive rate of TNM in stage I + II and III + IV in 50.79% and 84.21% respectively, there was significant difference between the two groups (X2=15.038, P=0.000); the expression of S100A14 protein in different age, different gender, different parts of the tumor in adenocarcinoma, the there was no significant difference between the expression of.7 (P0.05) by Spearman test SPSS17.0 software analysis showed that in colorectal adenocarcinoma tissues related to HER2 and EGFR (r=0.28, P=0.002), positive HER2 and S100A14 was positively correlated (r=0.309, P=0.001), EGFR and S100A14 were positively correlated (r=0.564, P=0.000). Conclusion: 1 HER2, EGFR. Over expression of S100A14 protein in colorectal adenocarcinoma was significantly higher than that in non tumor mucosa, Biao Mingsan, who may be involved in the carcinogenesis of.2, HER2, EGFR, S100A14 protein expression and differentiation, lymph node metastasis, invasion depth and TNM III + IV, EGFR, showed that HER2, S100A14 and The malignant biological behavior of colorectal adenocarcinoma is related to.3. The expression of HER2, EGFR and S100A14 protein in colorectal adenocarcinoma is 22, which indicates that there may be interaction between the three pathways in the development and progression of colorectal cancer.

【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R735.34

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