肺鱗癌間質(zhì)中CAFs與LVD、MVD的關(guān)系及其臨床意義
本文選題:肺鱗狀細(xì)胞癌 切入點(diǎn):FAP-1 出處:《青島大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:目的:本文觀察肺鱗狀細(xì)胞癌的間質(zhì)中被成纖維細(xì)胞激活蛋白1(FAP-1)染色的腫瘤相關(guān)成纖維細(xì)胞(CAFs),研究其與間質(zhì)中微血管密度(MVD)、淋巴管密度(LVD)的關(guān)系,探討CAFs對(duì)肺鱗狀細(xì)胞癌患者的總生存期(OS)的影響。方法:本研究選擇63例肺鱗狀細(xì)胞癌標(biāo)本為研究對(duì)象,均來(lái)自于2011年1月份至2012年12月份在青島市市立醫(yī)院的胸外科行肺切除術(shù)的患者,所獲得的病例中男性為58例,女性為5例。根據(jù)第七版美國(guó)癌癥聯(lián)合會(huì)(AJCC)的TNM分期原則對(duì)所選擇的所有63例病例進(jìn)行分期:I期為29例,Ⅱ期為19例,Ⅲ期為15例。所選病例的組織切片分別進(jìn)行兔抗人FAP-1多克隆抗體的免疫組織化學(xué)法染色,鼠抗人原始造血細(xì)胞(CD34)單克隆抗體的免疫組織化學(xué)法染色,鼠抗人D2-40單克隆抗體的免疫組織化學(xué)法染色,在病理專家的閱片后進(jìn)行評(píng)估。根據(jù)腫瘤間質(zhì)中陽(yáng)性著色細(xì)胞的百分比來(lái)對(duì)腫瘤相關(guān)成纖維細(xì)胞進(jìn)行FAP-1著色的評(píng)估,再依據(jù)著色細(xì)胞所占的比例判定分?jǐn)?shù):0=沒(méi)有著色;1=1%-10%;2=11%-50%;3"g50%。在本研究中采用50%作為分割點(diǎn),FAP-1評(píng)分高于3時(shí)被認(rèn)為是高表達(dá),即為CAFs豐富組,低于3分為低表達(dá),即為CAFs貧乏組。對(duì)于淋巴管的要求為,鏡下觀察只要與周邊的其他組織存在有較為明確的界限的任何一個(gè)細(xì)胞質(zhì)內(nèi)呈棕色染色的內(nèi)皮細(xì)胞或內(nèi)皮細(xì)胞群,均規(guī)定稱之為間質(zhì)內(nèi)的一條淋巴管。對(duì)于微血管的要求為,任何一個(gè)細(xì)胞質(zhì)內(nèi)成淡黃色或棕黃色的內(nèi)皮細(xì)胞或內(nèi)皮細(xì)胞簇,而且與周邊環(huán)境內(nèi)腫瘤細(xì)胞及結(jié)締組織成分有明顯分界的,則規(guī)定算作為間質(zhì)內(nèi)的一條微血管。兩者分別取4個(gè)視野的讀數(shù)的均值作為L(zhǎng)VD、MVD。在本研究中對(duì)所選取的所有63例術(shù)后患者進(jìn)行規(guī)范的密切的跟隨訪查,跟隨訪查的最終時(shí)間結(jié)束于2015年12月31日。在本研究中所獲得的全部數(shù)據(jù)應(yīng)用SPSS 17.0軟件進(jìn)行相應(yīng)處理,對(duì)CAFs與LVD、CAFs與MVD、CAFs與各臨床病理因素之間關(guān)系的研究均采用卡方檢驗(yàn)進(jìn)行分析;對(duì)于總生存期的預(yù)后評(píng)估,應(yīng)用Cox比例風(fēng)險(xiǎn)模型進(jìn)行分析。P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果:FAP-1的表達(dá)定位于腫瘤間質(zhì)細(xì)胞內(nèi),以50%作為分界點(diǎn),CAFs豐富組即FAP-1高表達(dá)組為27例,CAFs貧乏組即FAP-1低表達(dá)組為36例;肺鱗狀細(xì)胞癌的間質(zhì)內(nèi)CAFs與肺鱗狀細(xì)胞癌患者有無(wú)淋巴結(jié)轉(zhuǎn)移,與患者的腫瘤細(xì)胞的分化程度有關(guān),差異具有統(tǒng)計(jì)學(xué)意義(P㩳0.05),而與肺鱗狀細(xì)胞癌患者的性別、年齡,是否吸煙、TNM分期均無(wú)關(guān),差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05);肺鱗狀細(xì)胞癌患者間質(zhì)內(nèi)CAFs豐富組的微血管密度相比較于貧乏組的微血管密度要高,此差異具有統(tǒng)計(jì)學(xué)意義(P㩳0.05);肺鱗狀細(xì)胞癌患者間質(zhì)內(nèi)CAFs豐富組的淋巴管密度相比較于貧乏組的淋巴管密度要高,此差異具有統(tǒng)計(jì)學(xué)意義(P㩳0.05);肺鱗狀細(xì)胞癌患者的三年總生存期(OS)與間質(zhì)內(nèi)CAFs的密度相關(guān),差異具有統(tǒng)計(jì)學(xué)意義(P㩳0.05);肺鱗狀細(xì)胞癌患者的三年總生存期(OS)與淋巴結(jié)是否轉(zhuǎn)移淋巴結(jié)轉(zhuǎn)移相關(guān),差異具有統(tǒng)計(jì)學(xué)意義(P㩳0.05)。結(jié)論:本研究表明肺鱗狀細(xì)胞癌間質(zhì)中CAFs與LVD、MVD的增加呈顯著相關(guān),肺鱗狀細(xì)胞癌間質(zhì)內(nèi)的CAFs是肺鱗狀細(xì)胞癌患者不良預(yù)后的一重要影響因素。
[Abstract]:Objective: To observe the lung squamous cell carcinoma by interstitial fibroblast activation protein 1 (FAP-1) staining of tumor associated fibroblasts (CAFs), and study the microvessel density in the stroma (MVD), lymphatic vessel density (LVD) relationship, on overall survival of patients with lung squamous cell cancer CAFs (OS) effect. Methods: This study selected 63 cases of lung squamous cell carcinoma specimens as the research object, from 2011 January to 2012 December in Qingdao Municipal Hospital Department of thoracic surgery underwent pulmonary resection obtained in cases of male 58 cases, female 5 cases according to the article. Seventh edition of the American Joint Committee on cancer (AJCC) TNM staging principle for all 63 cases selected for stage I 29 cases, 19 cases of stage II, III 15 cases. Immunohistochemical tissue sections were selected cases of Rabbit anti human FAP-1 polyclonal antibody histochemical staining. Mouse anti human primary The beginning of hematopoietic stem cells (CD34) immunohistochemistry of monoclonal antibody staining, immunohistochemistry of mouse anti human D2-40 monoclonal antibody staining, evaluated in reading experts. According to the pathological evaluation the percentage of positive cells in tumor stroma to tumor associated fibroblasts by FAP-1 staining, then according to the for coloring the proportion of cells scores: 0= 1=1%-10%; 2=11%-50%; no coloring; 3 "g50%. 50% used in this research as the dividing point, FAP-1 score higher than 3 is considered high expression, namely CAFs rich group, less than 3 for the low expression of CAFs is poor for lymphatic requirements group. As observed any cytoplasm as long as there is with other organizations around the boundaries clear in brown staining of endothelial cells or cells, are called a shower set interstitial Pakistan pipe for micro blood. The requirements for endothelial cells or cell clusters in the cytoplasm of any light yellow or brown yellow, and the composition and surrounding environment within tumor cells and connective tissue has obvious boundary, provides regarded as interstitial microvascular. A mean respectively take 4 vision readings as LVD, MVD. in the study of the selected 63 cases of all patients were closely follow the norms established following the final visit time ended in December 31, 2015. Obtained in this study all the data using SPSS 17 software processed, CAFs and LVD, CAFs and MVD, study the relationship between CAFs and the clinicopathological factors were analyzed by chi square test; prognosis for overall survival, Cox proportional hazard model was used for analysis of.P0.05 difference was statistically significant. Results: the expression of FAP-1 in tumor Tumor interstitial cells, with 50% as cut-off point, CAFs rich group which is the high expression of FAP-1 group was 27 cases, CAFs group is the lack of FAP-1 low expression group was 36 cases; patients with squamous cell carcinoma of the lung interstitial CAFs and squamous cell carcinoma of the lung and lymph node metastasis, differentiation degree and patients the tumor cells, the difference was statistically significant (P? 0.05), and patients with lung squamous cell carcinoma of the gender, age, smoking, TNM stage were independent, no statistically significant difference (P0.05); microvessel density in patients with squamous cell carcinoma of lung interstitial CAFs rich group compared to the poor group of micro the vascular density is higher, the difference was statistically significant (P? 0.05); lung squamous cell carcinoma patients with interstitial CAFs rich group of lymphatic vessel density compared to the poor group of lymphatic vessel density is higher, the difference was statistically significant (P? 0.05); three years overall survival in patients with squamous cell carcinoma of the lung. (OS) With interstitial CAFs density, the difference was statistically significant (P? 0.05); three years overall survival in patients with lung squamous cell carcinoma (OS) and lymph node metastasis of lymph node metastasis, the difference was statistically significant (P? 0.05). Conclusion: This study suggests that interstitial lung squamous cell carcinoma CAFs and LVD were significantly related to increased MVD, squamous cell carcinoma of the lung interstitial CAFs is an important influencing factor of poor prognosis in patients with squamous cell carcinoma of the lung.
【學(xué)位授予單位】:青島大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R734.2
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