【作者】 周和平；

【导师】 李向东；

【作者基本信息】 苏州大学 ， 神经外科， 2008， 硕士

【摘要】 目的:a.研究核增殖抗原Ki-67、PCNA、基质金属蛋白酶-9(MMP-9)在垂体腺瘤中的表达;b.研究Ki-67、PCNA与MMP-9在垂体腺瘤中表达的相互关系;c.通过研究侵袭性、非侵袭性及复发性垂体腺瘤组织中Ki-67、PCNA、MMP-9的表达差异,为垂体腺瘤的治疗提供指导。材料与方法:1.收集我院2002年1月—2008年3月临床资料完整的垂体腺瘤患者手术标本86例,为研究对象,均经10%的中性甲醛固定、石蜡包埋。回顾这些病例的详细临床资料,本文研究采用Hardy-Wilson及Knosp分级、分期标准,结合术中切除的硬膜及瘤周垂体组织经病理证实肿瘤细胞浸润,判断垂体腺瘤的侵袭性,将肿瘤标本分为非侵袭性组(44例)、侵袭性组(42例),其中侵袭性组中复发9例。2.采用免疫组化SP法分别检测两组垂体腺瘤组织石蜡切片中核增殖抗原Ki-67、PCNA、MMP-9的表达;3.统计分析垂体腺瘤组织中Ki-67、PCNA、MMP-9的表达在两组病例中的差异,研究Ki-67、PCNA、MMP-9在垂体腺瘤中表达的相互关系,并进一步分析它们与垂体腺瘤侵袭性及复发的关系。结果:1、Ki-67、PCNA在86例垂体腺瘤组织中表达与患者性别无关,与肿瘤大小有关,大腺瘤或巨腺瘤表达明显高于小腺瘤。非侵袭和侵袭性腺瘤组中,Ki-67LI值为1.83±0.85和3.36±1.17;PCNA阳性表达率分别为22.73%(10/44)和57.14%(24/42),经统计学t检验和X~2,Ki-67及PCNA在侵袭性组表达明显高于非侵袭性组(P＜0.01)。2、MMP-9在垂体腺瘤组织中表达与患者性别无关,与肿瘤大小有关,大腺瘤或巨腺瘤表达明显高于小腺瘤。非侵袭和侵袭性组中,MMP-9阳性表达率分别为47.73%(21/44)和73.81%(31/42)。经统计学X~2检验,MMP-9侵袭性组表达明显高于非侵袭性组(P＜0.01)。3、侵袭性腺瘤复发组与非复发组中及复发组复发前后PCNA阳性表达率分别为55.56%,57.58%和66.67%,无明显统计学差异(p＞0.05)。在侵袭性腺瘤复发组复发前后,Ki-67LI值分别为3.52±1.23,3.58±0.67,无明显统计学差异(p＞0.05);复发组Ki-67LI值3.52±1.23,明显高于非复发组Ki-67LI值3.32±1.06,有统计学意义(P＜0.01).在侵袭性腺瘤复发组复发前后与非复发组中,MMP-9阳性表达率分别为88.89%,100%和69.70%,经统计学X2检验,MMP-9在侵袭性腺瘤复发组复发前后与非复发组中有显著差异(P＜0.01)。4.Ki-67、PCNA及MMP-9在垂体腺瘤中表达呈正相关,在垂体腺瘤的侵袭性生长及复发中起协同作用。结论:1.Ki-67、PCNA细胞核增殖抗原在侵袭性垂体腺瘤中表达明显高于非侵袭性腺瘤,提示Ki-67、PCNA可以作为判断垂体腺瘤侵袭性的重要标记物。2.Ki-67LI值3%可以作为区分非侵袭性和侵袭性垂体腺瘤的Ki-67阈值,Ki-67LI值越高,预示侵袭性垂体腺瘤易复发。3.侵袭性垂体腺瘤MMP-9蛋白表达较非侵袭性腺瘤显著增高,MMP-9蛋白表达复发组明显高于非复发组,且复发后较复发前表达明显增高,提示MMP-9在垂体腺瘤的侵袭性生长及肿瘤复发中扮演重要作用。4.Ki-67、PCNA及MMP-9在垂体腺瘤中表达呈正相关,在垂体腺瘤的侵袭性生长及复发中起协同作用,三者结合可作为判断垂体腺瘤侵袭性及预后的重要参考指标。更多还原

【Abstract】 Objective:In our study,we observe the expression of the Ki-67,PCNA antigen and MMP-9 in pituitary adenoma tissues.We observe the expression of theKi-67,PCNA antigen and MMP-9 in invasive pituitary adenoma and noninvasive pituitary adenoma,we compare the expression difference of Ki-67,PCNA antigen and MMP-9 between two groups, analysis the relationship with the invasion of pituitary adenomas.Methods:1.86 pituitary adenomas specimens removed in our department were collected, all fixed with 10%neutral formalin and then paraffin embedded.Every case history was detailedly reviewed,and all specimens were divided into invasive group(42 cases)and noninvasive group(44 cases)by adopting Hardy-Wilson and Knosp standard.2.It was examined by immunohistochemistry of SP methods that expression of Ki-67,PCNA antigen and MMP-9 in these slices of specimens.3.Finally we discuss the correlation between expression of Gal-3 and Ki-67 antigen,and then analyze the relationship between expression of Ki-67,PCNA antigen and MMP-9 with invasiveness of the pituitary adenomas.Results:1.The expression of Ki-67 and PCNA is no significant relationship with the sex in 86 pituitary adenoma,There is significant difference with diameter of the tumor,the expression of macroadenoma is higher than the small adenoma.The positive expression fig of Ki-67L1 in non-invasive pituitary adenomas andinvasive pituitary adenomas is 1.83±0.85,3.36±1.17 respectively.The positive expression rate of PCNA in non-invasive pituitary adenomas and invasive pituitary adenomas is 22.73%(10/44),57.14%(24/42) respectively.There is significant difference between 2 groups(p＜0.01).2.The expression of MMP-9 is no significant relationship with the sex in 86 pituitary adenoma,There is significant difference with diameter of the tumor,the expression of macroadenoma is higher to the small adenoma.The positive expression rate of MMP-9 in non-invasive pituitary adenomas and invasive pituitary adenomas is 47.73%(21/44),73.81%(31/42)respectively.There is significant difference between 2 groups(p＜0.01).3.The positive expression rate of PCNA in recur-invasive pituitary adenomas,non recur-invasive pituitary adenomas and afterwards recur-invasive pituitary adenomas is 55.56%, 57.58%,66.67%respectively.There is no significant difference between 3 groups(p＞0.05). The positive expression fig of Ki-67LI is 3.52±1.23,3.58±0.67 respectively.There is significant difference between 2 groups(p＜0.01).The positive expression rate of MMP-9 is 88.89%,100%,69.70%respectively.There is significant difference between 3 groups(p＜0.01).4.There is a significant correlation between expression level of Ki-67、PCNA and MMP-9.Conclusions:1.The expression of Ki-67 and PCNA in invasive pituitary adenomas is higher than that in non-invasive pituitary adenomas,the expression quantity is increased with invasion extent,indicate the Ki-67 and PCNA might be parameter in judgement invasion of pituitary adenoma.2.The value 3%of Ki-67 may be threshold value to distinguish non-invasive pituitary adenomas andinvasive pituitary adenomas,the value is higher,indicate that andinvasive pituitary adenomas is easy recurrence.3.The expression of MMP-9 is higher in invasive pituitary adenoma to non-invasive pituitary adenomas,The expression of MMP-9 is higher in recur pituitary adenoma to non recur pituitary adenoma.MMP-9 plays an important role in invasive growth and recur of pituitary adenoma.4.There is a significant correlation between the expression of Ki-67,PCNA and MMP-9 in pituitary ademona,plays an cooperative effect invasive growth and recur of pituitary adenoma,the Ki-67,PCNA and MMP-9 might be parameter in judgement invasion and prognosis of pituitary adenoma.更多还原