本文選題：多形性腺瘤 + 腺樣囊性癌��； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：研究背景與目的淚腺腫瘤是臨床上較常見(jiàn)的眼眶疾病之一,約占眼眶腫瘤的7%-13%,其中上皮性腫瘤約占淚腺腫瘤的70%。因具有眼突、眼球受壓向內(nèi)下方移位、上瞼腫脹、部分患者可出現(xiàn)視物模糊和復(fù)視,惡性腫瘤患者更有持續(xù)性疼痛等臨床表現(xiàn),嚴(yán)重影響患者外觀與日常生活。良性腫瘤易復(fù)發(fā)和惡變;惡性腫瘤易早期侵襲轉(zhuǎn)移,10年生存率不足20%。所以近年來(lái),隨著分子生物學(xué)的發(fā)展,尋找新的影響淚腺上皮性腫瘤預(yù)后的分子生物學(xué)指標(biāo)成為臨床研究的重要課題之一,這對(duì)疾病預(yù)后的預(yù)測(cè)并給予針對(duì)性治療,改善預(yù)后具有重要意義。環(huán)氧合酶(Cyclooxygenase,COX)是花生四烯酸轉(zhuǎn)化為前列腺素過(guò)程的重要限速酶,分為兩種亞型,即:COX-1,COX-2。COX-1在多數(shù)正常組織中表達(dá),其m RNA及蛋白在人體組織中相對(duì)恒定,在維持組織和細(xì)胞的正常生理功能中發(fā)揮作用。COX-2在正常人體組織中極少表達(dá)或不表達(dá),近些年來(lái),研究發(fā)現(xiàn)COX-2在多數(shù)腫瘤中都具有高的陽(yáng)性率,COX-2通路生成的前列腺素(prostaglandin,PG)在致癌過(guò)程中有重要作用。COX-2被認(rèn)為可以通過(guò)影響腫瘤細(xì)胞的生長(zhǎng)、增殖、侵襲、轉(zhuǎn)移及血管生長(zhǎng)而促進(jìn)多種腫瘤的發(fā)生發(fā)展,這些腫瘤包括胃癌、結(jié)腸癌、肺癌、乳腺癌、涎腺腫瘤等,并影響著腫瘤的預(yù)后�；|(zhì)金屬蛋白酶-9(metalloproteninase-9)是MMPs家族成員之一,是一種鈣鋅依賴性蛋白。降解基底膜中的Ⅳ型膠原蛋白為其主要作用。腫瘤的侵襲和轉(zhuǎn)移是多步驟的復(fù)雜過(guò)程,其中ECM的降解是其關(guān)鍵環(huán)節(jié),基質(zhì)金屬蛋白酶家族(MMPs)是參與ECM降解的重要蛋白酶。由于Ⅳ型膠原是構(gòu)成基底膜的重要組成部分,因此,MMP-9因?yàn)槟芙到饣啄さ蘑粜湍z原蛋白而被認(rèn)為與腫瘤的浸潤(rùn)和轉(zhuǎn)移有關(guān)。除此之外,在腫瘤侵襲轉(zhuǎn)移過(guò)程中,MMP-9還可以促進(jìn)新生血管形成。在大腸癌、胰腺癌研究中發(fā)現(xiàn)COX-2、MMP-9在通路上有著交互作用,共同參與腫瘤的發(fā)生、發(fā)展、侵襲轉(zhuǎn)移,成為影響腫瘤預(yù)后的重要因素。但是二者在淚腺腫瘤中的表達(dá)在國(guó)內(nèi)外文獻(xiàn)中報(bào)道甚少。本研究采用免疫組織化學(xué)的方法檢測(cè)了淚腺腺樣囊性癌(adenoid cystic carcinoma,ACC)、多形性腺瘤(pleomorphic adenoma,PA)和瘤旁淚腺組織中COX-2、MMP-9的表達(dá)情況,觀察其與淚腺上皮腫瘤臨床預(yù)后的關(guān)系,為淚腺上皮腫瘤復(fù)發(fā)預(yù)測(cè)以及針對(duì)性治療提供依據(jù)。1研究對(duì)象與方法1.1研究對(duì)象本研究收集2004年1月—2013年1月經(jīng)鄭州大學(xué)第一附屬醫(yī)院眼科手術(shù)治療,病理科確診且隨訪資料完整的淚腺上皮性腫瘤患者標(biāo)本66例,其中淚腺多形性腺瘤37例,腺樣囊性癌29例。另取8例瘤旁淚腺組織作為對(duì)照。淚腺多形性腺瘤組,男14例,女23例;年齡20-82歲,中位年齡45歲。淚腺腺樣囊性癌組,男14例,女15例;年齡9-77歲,中位年齡47歲;其中腺樣-管狀型15例,實(shí)性型14例;所有腫瘤患者術(shù)前均未進(jìn)行放、化療。1.2研究方法采用免疫組織化學(xué)的方法檢測(cè)了淚腺腺樣囊性癌、多形性腺瘤和瘤旁淚腺組織中COX-2、MMP-9的表達(dá)情況。對(duì)所有患者均行電話隨訪或門診復(fù)查,隨訪自手術(shù)之日作為起點(diǎn),以腫瘤復(fù)發(fā)作為結(jié)局事件,記錄隨訪結(jié)果。采用SPSS17.0統(tǒng)計(jì)軟件對(duì)所得數(shù)據(jù)進(jìn)行分析。臨床標(biāo)本COX-2、MMP-9表達(dá)的組間比較采用Mann-Whitney U秩和檢驗(yàn),兩者之間相關(guān)性采用spearman等級(jí)相關(guān)分析,與復(fù)發(fā)的關(guān)系分析采用連續(xù)性校正χ2檢驗(yàn),以P0.05表示差異有統(tǒng)計(jì)學(xué)意義。2結(jié)果2.1 COX-2、MMP-9在瘤旁淚腺組織、多形性腺瘤、淚腺腺樣囊性癌中的表達(dá)2.1.1 COX-2陽(yáng)性表達(dá)主要位于腫瘤細(xì)胞的胞漿內(nèi),瘤旁淚腺組織中未見(jiàn)COX-2的陽(yáng)性表達(dá)。COX-2在淚腺腺樣囊性癌組及多形性腺瘤組中的陽(yáng)性表達(dá)率分別為72.4%和32.4%,腺樣囊性癌組陽(yáng)性表達(dá)明顯高于多形性腺瘤組,兩組間差異具有統(tǒng)計(jì)學(xué)意義(Z=-3.671;P0.05)。2.1.2 MMP-9陽(yáng)性表達(dá)定位于腫瘤細(xì)胞的胞漿或胞核。瘤旁淚腺組織中未見(jiàn)MMP-9的陽(yáng)性表達(dá)。MMP-9在淚腺腺樣囊性癌組及多形性腺瘤組中的表達(dá)陽(yáng)性率分別為65.5%和21.6%,腺樣囊性癌組陽(yáng)性表達(dá)明顯高于多形性腺瘤組,兩組間差異具有統(tǒng)計(jì)學(xué)意義(Z=-4.136;P0.05)2.2 COX-2、MMP-9在淚腺上皮腫瘤中表達(dá)的相關(guān)性Spearman相關(guān)分析顯示,在66例淚腺上皮腫瘤中,COX-2與MMP-9表達(dá)呈正相關(guān)(r=0.673;P0.01)2.3.COX-2、MMP-9與淚腺腫瘤患者復(fù)發(fā)關(guān)系隨訪結(jié)果發(fā)現(xiàn)66例淚腺上皮腫瘤患者中,腺樣囊性癌組復(fù)發(fā)17例,多形性腺瘤組復(fù)發(fā)5例,共復(fù)發(fā)22例,經(jīng)連續(xù)性校正χ2檢驗(yàn),COX-2、MMP-9陽(yáng)性者淚腺上皮性腫瘤的復(fù)發(fā)風(fēng)險(xiǎn)顯著大于陰性者(P0.05)。24例COX-2/MMP-9陽(yáng)性者,復(fù)發(fā)17例,復(fù)發(fā)率達(dá)70.8%;30例COX-2/MMP-9陰性者有1例復(fù)發(fā),復(fù)發(fā)率僅為3.3%。3結(jié)論(1)COX-2、MMP-9在瘤旁淚腺組織中均未見(jiàn)陽(yáng)性表達(dá),而在淚腺上皮性腫瘤中有較高表達(dá),且腺樣囊性癌組陽(yáng)性表達(dá)明顯高于多形性腺瘤組;(2)COX-2、MMP-9在淚腺上皮性腫瘤中的表達(dá)呈正相關(guān)。提示兩者可能存在交互作用;(3)在淚腺上皮性腫瘤中,COX-2、MMP-9陽(yáng)性表達(dá)患者復(fù)發(fā)風(fēng)險(xiǎn)顯著大于陰性者,提示COX-2、MMP-9的表達(dá)與淚腺上皮性腫瘤的預(yù)后復(fù)發(fā)密切相關(guān)。
[Abstract]:Background and objective lacrimal gland tumor is one of the most common orbital diseases, which accounts for 7%-13% of the orbital tumor, in which the epithelial tumor accounts for the 70%. of the lacrimal gland tumor, which has an eye process, the pressure of the eyeball is moved downward, the upper eyelid is swollen, some patients can appear blurred visual substance and diplopia, and the patients with malignant tumor are more persistent pain and so on. The bed performance seriously affects the appearance and daily life of the patients. The benign tumor is prone to relapse and malignancy; the malignant tumor is prone to early invasion and metastasis, and the 10 year survival rate is less than 20%., so in recent years, with the development of molecular biology, it is one of the important topics in the clinical study to find new molecular biological indicators that affect the prognosis of lacrimal gland epithelial tumors. Cyclooxygenase (COX) is an important rate limiting enzyme for the transformation of Arachis four eNIC acid into prostaglandin process, which is divided into two subtypes, namely, COX-1, COX-2.COX-1 in most normal tissues, and m RNA and protein are relatively constant in human tissues. To maintain the normal physiological functions of tissues and cells,.COX-2 is rarely expressed or expressed in normal human tissues. In recent years, studies have found that COX-2 has a high positive rate in most tumors. The prostaglandin (prostaglandin, PG) generated by the COX-2 pathway plays an important role in the carcinogenesis, and.COX-2 is considered to be able to pass through the shadow. The growth, proliferation, invasion, metastasis and vascular growth of tumor cells promote the development of a variety of tumors. These tumors include gastric cancer, colon cancer, lung cancer, breast cancer, salivary gland tumor and so on, and affect the prognosis of the tumor. Matrix metalloproteinase -9 (metalloproteninase-9) is one of the members of the MMPs family, a calcium zinc dependent protein. The main role of collagen type IV collagen in the basement membrane is to affect the invasion and metastasis of the tumor. The degradation of ECM is the key link, and the matrix metalloproteinase family (MMPs) is an important protease involved in the degradation of ECM. As type IV collagen is an important component of the basement membrane, MMP-9 is degraded because of its degradation. Type IV collagen in the basement membrane is considered to be associated with tumor invasion and metastasis. In addition, MMP-9 can also promote neovascularization during the invasion and metastasis of the tumor. In the study of colorectal cancer, the study of pancreatic cancer found that COX-2 and MMP-9 have interaction on the pathway, and participate in the occurrence, development, invasion and metastasis of the tumor. But the expression of the two in lacrimal gland tumor is rarely reported in the domestic and foreign literature. The present study used immunohistochemical method to detect the expression of adenoid cystic carcinoma (ACC), pleomorphic adenoma (PA) and the expression of COX-2 in the lacrimal gland tissue adjacent to the tumor. The relationship between the clinical prognosis and the prognosis of lacrimal gland epithelial tumors was investigated to provide a basis for.1 research and method 1.1 research objects and methods for the treatment of lacrimal gland epithelial tumor. The study collected the eye surgery of the First Affiliated Hospital of Zhengzhou University from January 2004 to 2013, and the pathology department confirmed and followed up the complete lacrimal gland epithelium. There were 66 cases of tumor patients, including 37 cases of pleomorphic adenoma of lacrimal gland, 29 cases of adenoid cystic carcinoma and 8 cases of lacrimal gland tissue adjacent to the lacrimal gland as control. The lacrimal gland pleomorphic adenoma group, 14 male, 23 case; age 20-82, age 45. The lacrimal gland adenoid cystic carcinoma group, 14 men, 15 cases; age 9-77 years, middle age 47 years; adenoid tubular 15, 15 cases, 14 cases of solid type; all tumor patients were not placed before operation. The.1.2 method of chemotherapy was used to detect the expression of COX-2 and MMP-9 in lacrimal gland adenoid cystic carcinoma, pleomorphic adenoma and lacrimal gland tissue adjacent to the tumor. SPSS17.0 statistical software was used to analyze the results of the recurrence as an outcome event. The SPSS17.0 statistical software was used to analyze the data. The comparison of the expression of COX-2 and MMP-9 was compared with the Mann-Whitney U rank and test. The correlation between the two groups was analyzed by Spearman grade correlation analysis. The relationship analysis with the recurrence was analyzed by the continuity correction chi 2 test, and expressed in P0.05. The difference was statistically significant.2 results 2.1 COX-2, MMP-9 in the lacrimal gland tissue, pleomorphic adenoma, and adenoid cystic carcinoma of lacrimal gland, the expression of 2.1.1 COX-2 was mainly located in the cytoplasm of the tumor cells. There was no positive expression of COX-2 in the lacrimal gland tissue beside the tumor, and the positive expression of.COX-2 in the lacrimal gland adenoid cystic carcinoma group and the pleomorphic adenoma group was expressed. The positive expression of the adenoid cystic carcinoma group was significantly higher than that of the pleomorphic adenoma group. The difference between the two groups was statistically significant (Z=-3.671; P0.05), the positive expression of.2.1.2 MMP-9 was located in the cytoplasm or nucleus of the tumor cells. There was no MMP-9 positive expression of MMP-9 in the lacrimal gland tissue beside the tumor, and in the lacrimal gland adenoid cystic carcinoma group and the polygonous gland The positive rates of expression in the tumor group were 65.5% and 21.6% respectively. The positive expression of the adenoid cystic carcinoma group was significantly higher than that of the pleomorphic adenoma group. The difference between the two groups was statistically significant (Z=-4.136; P0.05) 2.2 COX-2. The correlation of MMP-9 expression in the lacrimal gland epithelial tumor was revealed by Spearman correlation analysis. In 66 cases of lacrimal gland epithelial tumors, the expression of COX-2 and MMP-9 was expressed. The follow-up results of positive correlation (r=0.673; P0.01) 2.3.COX-2, MMP-9 and lacrimal gland tumor recurrence found that in 66 cases of lacrimal gland epithelial tumor, there were 17 cases of adenoid cystic carcinoma, 5 recurrences in the pleomorphic adenoma group, 22 cases with a total recurrence. The recurrence rate of COX-2 and MMP-9 positive patients was significantly greater than that of negative carcinoma with COX-2 and MMP-9 positive. There were 17 cases of COX-2/MMP-9 positive in.24 (P0.05), recurrence rate of 70.8%, 30 cases of COX-2/MMP-9 negative, recurrence rate of only 3.3%.3 conclusion (1) COX-2, MMP-9 in lacrimal gland tissue near the tumor, but high expression in lacrimal gland epithelial tumor, and the positive expression of adenoid cystic carcinoma group was significantly higher than that of pleomorphic adenoma (2) the expression of COX-2 and MMP-9 in lacrimal gland epithelial tumor is positively correlated. It suggests that there may be interaction between them. (3) in lacrimal gland epithelial tumors, the recurrence risk of COX-2 and MMP-9 positive patients is significantly greater than that of negative ones, suggesting that the expression of COX-2, MMP-9 is closely related to the recurrence of lacrimal gland epithelial tumor.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R739.7

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