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  本文選題：趨化因子受體CCR7　切入點：血管內(nèi)皮生長因子-C(VEGF-C)　出處：《瀘州醫(yī)學(xué)院》2010年碩士論文　論文類型：學(xué)位論文

【摘要】： 目的：檢測喉鱗狀細(xì)胞癌(1 aryngeal squamous cell carcinoma, LSCC,簡稱喉鱗癌)、癌旁正常喉黏膜組織及喉部良性病變聲帶息肉組織中趨化因子受體CCR7 (C-C Chemokine Receptor 7,CCR7)及血管內(nèi)皮生長因子-C(vascular endothelial growth factor,VEGF-C)的表達(dá)和微淋巴管密度值(lymphatic microvessel density,LMVD),并探討三者間的相互關(guān)系及其與喉癌淋巴結(jié)轉(zhuǎn)移的關(guān)系。方法：選取瀘州醫(yī)學(xué)院附屬醫(yī)院耳鼻咽喉-頭頸外科2008年1月至2009年10月行手術(shù)切除并經(jīng)病理檢查診斷的40例喉部鱗狀細(xì)胞癌的存檔蠟塊為實驗組；40例癌旁正常喉黏膜組織(距癌組織5mm以上經(jīng)病理證實為正常喉黏膜)及20例經(jīng)病理檢查證實為喉良性病變組織聲帶息肉為對照組。全部病例術(shù)前均行喉部高分辨率CT檢查,且未行化療或放療。應(yīng)用免疫組織化學(xué)方法檢測以上組織中CCR7、VEGF-C及D2-40的表達(dá),對D2-40陽性脈管進行LMVD計數(shù),并結(jié)合臨床病歷資料進行統(tǒng)計學(xué)分析,分析CCR7、VEGF-C及LMVD與喉癌臨床病理特征的關(guān)系,以及三者之間的相互關(guān)系。結(jié)果：喉癌組織與癌旁正常黏膜組織及聲帶息肉組織中CCR7的表達(dá)差異顯著,CCR7主要表達(dá)于喉癌細(xì)胞的胞質(zhì)和／或胞膜,陽性片可見胞質(zhì)和／或胞膜上有棕黃色的片狀物質(zhì),而在癌旁正常黏膜上皮少量陽性表達(dá),在聲帶息肉組織中幾乎無表達(dá)；40例喉癌組織中CCR7的表達(dá)陽性24例,陰性16例,陽性率60.0%(24/40), CCR7與喉癌淋巴結(jié)轉(zhuǎn)移密切相關(guān),而與患者性別、年齡、是否吸煙、細(xì)胞分化程度、臨床分型及T分期無關(guān)。喉癌組織與癌旁正常黏膜組織及聲帶息肉組織中VEGF-C的表達(dá)差異顯著(P0.05),VEGF-C的陽性染色為棕黃色,主要表達(dá)在喉癌細(xì)胞的胞漿內(nèi),聲帶息肉組織及陰性對照組中少量表達(dá)；40例喉癌組織中VEGF-C的表達(dá)陽性19例,陰性21例,陽性率47.5%(19／40),VEGF-C表達(dá)與腫瘤細(xì)胞分化程度、臨床分型、T分期之間無顯著性差異(P＞0.05),而淋巴結(jié)轉(zhuǎn)移組陽性率及表達(dá)強度均高于非轉(zhuǎn)移組,差異顯著(P0.05)。D2-40較特異性地表達(dá)在淋巴管內(nèi)皮細(xì)胞,呈棕黃色顆粒狀,血管內(nèi)皮細(xì)胞未見表達(dá)；喉癌組織癌巢內(nèi)及外周間質(zhì)均可見淋巴管被擠壓成條索狀,散在或成簇分布；喉癌組織與癌旁正常黏膜組織及聲帶息肉組織中微淋巴管密度差異顯著(P0.05)；喉癌組織中微淋巴管密度在淋巴結(jié)轉(zhuǎn)移組明顯高于非轉(zhuǎn)移組,差異非常顯著(P0.01)。40例喉癌標(biāo)本中,VEGF-C和CCR7均為陽性表達(dá)者有17例,均為陰性表達(dá)者有15例,Kappa一致性相關(guān)檢驗表明,喉癌組織中VEGF-C和CCR7表達(dá)有較高的吻合度(K=0.600),且二者間的吻合度有統(tǒng)計學(xué)意義(P=0.000)。VEGF-C表達(dá)陽性的組織中LMVD平均值為(17.57±3.27)個／mm2,表達(dá)陰性者LMVD平均值為(10.26±3.77)個／mm2,兩者比較具有顯著性差異(P0.05)。喉癌組織中CCR7陽性表達(dá)者LMVD為(19.05±5.33)個／mm2,陰性表達(dá)者LMVD為(11.16±5.28)個／mm2,兩者相比,P0.01。結(jié)論：(1) CCR7與喉癌的淋巴結(jié)轉(zhuǎn)移有關(guān),VEGF-C與喉癌的淋巴管生成有關(guān),兩者具有協(xié)同作用,共同促進喉癌細(xì)胞的淋巴結(jié)轉(zhuǎn)移；(2)D2-40標(biāo)記淋巴管的特異性和敏感性較好,是新近發(fā)現(xiàn)較為理想的淋巴管標(biāo)記物,喉癌組織及邊緣區(qū)高LMVD與淋巴結(jié)轉(zhuǎn)移之間呈明顯相關(guān),提示淋巴管生成在喉癌淋巴結(jié)轉(zhuǎn)移中具有重要作用；(3)隨著CCR7表達(dá)強度的增加VEGF-C陽性分級隨之上升,LMVD均值也逐漸增加,LMVD均值的增加是與CCR7陽性強度平行的,即CCR7表達(dá)越強,LMVD均值越高,CCR7、VEGF-C與LMVD之間呈顯著相關(guān)性；(4) CCR7、VEGF-C和LMVD與喉癌的淋巴結(jié)轉(zhuǎn)移密切相關(guān),聯(lián)合檢測它們在內(nèi)鏡活檢組織中的表達(dá)有助于預(yù)測喉癌早期淋巴結(jié)轉(zhuǎn)移的發(fā)生。
[Abstract]:Objective: to detect laryngeal squamous cell carcinoma (1 aryngeal squamous cell carcinoma LSCC, referred to as laryngeal squamous cell carcinoma), chemokine receptor CCR7 in adjacent normal laryngeal mucosa tissues and laryngeal benign lesions of vocal cord polyp tissues (C-C Chemokine Receptor 7, CCR7) and vascular endothelial growth factor -C (vascular endothelial growth factor, VEGF-C). Expression and lymphatic microvessel density (lymphatic value microvessel density, LMVD), and to explore the relationship between the three and their relationship with lymph node metastasis of laryngeal carcinoma. Methods: paraffin blocks for the experimental group selected 40 cases of laryngeal squamous cell carcinoma of Otolaryngology Head and neck surgery in Affiliated Hospital of Luzhou Medical College from January 2008 to October 2009 underwent surgical resection and confirmed by pathological examination diagnosis; 40 cases of adjacent normal laryngeal mucosa tissue (5mm away from cancer tissue than normal laryngeal mucosa was confirmed by pathology) and 20 cases of pathologically confirmed Laryngeal Benign check Lesions of vocal cord polyps were treated as control group. The throat of high resolution CT examination in all cases before surgery, and without chemotherapy or radiotherapy. CCR7 immunohistochemical method was used to detect the expression of VEGF-C and D2-40 in the LMVD to count the number of D2-40 positive vessels, and combined with the clinical medical records data for statistical analysis, analysis CCR7, VEGF-C and LMVD and clinical features of laryngeal squamous cell carcinoma, and the relationship between the three. Results: the expression of CCR7 in laryngeal carcinoma and adjacent normal mucosa tissue and vocal cord polyp tissues significantly, cytoplasmic CCR7 is mainly expressed in laryngeal carcinoma cells and / or cell membrane, flaky material and brown yellow positive film cytoplasm and / or on the cell membrane, and in adjacent normal mucosa showed positive expression in vocal cord polyps almost no expression; 24 cases of positive expression of CCR7 in 40 cases of laryngeal carcinoma, 16 cases of yin and Yang The rate of 60% (24/40), CCR7 and lymph node metastasis in laryngeal cancer is closely related with gender, age, smoking, cell differentiation, clinical typing and staging of T. The differential expression of VEGF-C in laryngeal carcinoma and adjacent normal mucosa tissues and vocal polyp tissues showed positive staining (P0.05), VEGF-C brown, mainly expressed in the cytoplasm of laryngeal squamous cell carcinoma and polyp of vocal cord and negative control group in a small amount of expression; 19 cases of positive expression of VEGF-C in 40 cases of laryngeal carcinoma, 21 cases were negative, the positive rate was 47.5% (19 / 40), and the degree of differentiation of tumor cell VEGF-C expression, clinical classification, T significant differences between stages (P > 0.05), and lymph node metastasis group the positive rate and expression intensity were higher than those in the non metastasis group, significant difference (P0.05).D2-40 is specifically expressed in lymphatic endothelial cells, brownish yellow granules, expression of vascular endothelial cells; larynx Cancer nests and peripheral lymphatic interstitial were observed by extrusion into cords, scattered or clustered; laryngeal cancer tissue and adjacent normal mucosa and polyp of vocal cord lymphatic microvessel density in significant difference (P0.05) in laryngeal carcinoma; lymphatic microvessel density in lymph node metastasis group higher than the non metastatic group was significant difference (P0.01).40 cases of laryngeal carcinoma specimens, VEGF-C and CCR7 were positive expression in 17 cases were negative expression in 15 cases, Kappa consistency test showed that the agreement had higher VEGF-C and CCR7 expression in laryngeal squamous cell carcinoma (K=0.600), and the two the agreement was statistically significant (P=0.000).VEGF-C expression in LMVD positive tissues average (17.57 + 3.27) / mm2, negative expression of the average LMVD (10.26 + 3.77) / mm2, compared with significant difference (P0.05). The positive expression of CCR7 in laryngeal carcinoma LM VD (19.05 + 5.33) / mm2, the negative expression of LMVD (11.16 + 5.28) / mm2, P0.01. comparison, conclusion: (1) CCR7 laryngeal carcinoma and lymph node metastasis, VEGF-C and laryngeal cancer lymphangiogenesis, they have synergistic effect, promote lymph cells of laryngeal carcinoma node metastasis; (2) good D2-40 markers of lymphatic specificity and sensitivity, is a newly found ideal lymphatic markers, was significantly related between laryngeal carcinoma and the marginal zone of high LMVD and lymph node metastasis, suggesting that lymphangiogenesis plays an important role in lymph node metastasis in laryngeal carcinoma; (3) the expression of CCR7 increase the strength of VEGF-C positive grading increased, LMVD value increased gradually, increasing the mean value of LMVD is in parallel with the CCR7 positive intensity, the more expression of CCR7, LMVD value is higher, CCR7, between VEGF-C and LMVD showed a significant correlation; (4) CCR7, VEGF-C and LMVD and laryngeal The lymph node metastasis of cancer is closely related. The joint detection of their expression in endoscopic biopsy tissue is helpful to predict the occurrence of early lymph node metastasis in laryngeal carcinoma.

【學(xué)位授予單位】：瀘州醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2010
【分類號】：R739.65

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本文編號：1612005