乳腺癌前病变和乳腺癌中α、γ-tubulin蛋白表达的免疫荧光定量分析及其意义

目的:研究乳腺导管上皮不典型增生(ADH)、导管内癌(DCIS)及浸润性导管癌(IDC)中α-tubulin和Γ-tubulin表达的变化及其意义,进一步探讨中心体异常与乳腺癌发生发展的相关性。方法:研究样本被分为导管上皮不典型增生、导管内癌和浸润性导管癌3组,每组30例。采用流式细胞免疫荧光定量分析技术和免疫组织化学方法,检测上述各组中心体微管蛋白α-tubulin和Γ-tubulin表达水平,与30例正常乳腺组的检测结果比较,并进行统计学分析。结果:在全部样本组中α-tubulin及Γ-tubulin FITC标记的阳性细胞数均数不同,差异有显著性(P=0.000),浸润性导管癌组的过表达最高,正常组织组最低。α-tubulin、Γ-tubulin表达水平随着细胞增殖级别的增加和分化程度的变差呈增高趋势。除不典型增生组和导管内癌组两组间比较以外,其余各组间差异均有显著性(P=0.001)。在每组中α-tubulin和Γ-tubulin的表达程度无统计学差异(P<0.05),显示免疫荧光定量分析和免疫组织化学检测结果趋于一致。结论:乳腺癌发生的早期阶段即存在着中心体蛋白的过度表达,推测这种异常表达在促进细胞恶性转化、形成乳腺癌过程中可能扮演了重要角色。对于中心体蛋白过表达的检测,免疫荧光定量和免疫组化两种技术可相互补充。     

Maspin蛋白在乳腺癌与癌旁组织中的表达及其意义

目的:探讨Maspin蛋白在乳腺癌与癌旁组织中的表达及其意义.方法:采用免疫组化SP法检测104例浸润性乳腺癌、26例癌旁原位癌成分、63例癌旁导管上皮增生性病变(不典型增生20例、单纯性增生43例)及10例正常乳腺组织中Maspin蛋白的表达情况,同时分析浸润性乳腺癌组织中Maspin蛋白表达与病理组织学分级、淋巴结转移及ER、PR、c-erbB-2、Cath-D、VEGF表达的关系.结果:正常乳腺上皮细胞Maspin蛋白阳性反应主要位于细胞核,所有正常乳腺上皮细胞核均呈高表达( ～ ,100%),乳腺上皮单纯性增生、不典型增生、原位癌和浸润性乳腺癌细胞核Maspin蛋白高表达率分别为76.7%、65.0%、69.2%,和49.0%.从正常乳腺上皮到癌旁不典型增生细胞核Maspin蛋白高表达率呈渐趋下降趋势,不典型增生与原位癌的表达无明显差异,浸润性乳腺癌表达最低,Logistic回归模型分析不同组织细胞核Maspin蛋白高表达间存在显著差异(P＜0.05);而单纯性增生、不典型增生、原位癌和浸润性乳腺癌细胞浆Maspin蛋白高表达率分别为51.2%、85.0%、69.2%和63.5%,正常乳腺上皮未见细胞浆表达.不同组织Maspin蛋白的细胞浆表达同样有显著差异(P＜0.01),其中癌旁不典型增生较乳腺癌有更高的细胞浆表达.进一步研究发现浸润性乳腺癌细胞核Maspin蛋白表达与乳腺癌病理组织学分级及c-erbB-2表达呈负相关,与ER水平呈正相关;而与PR、Cath-D、VEGF的表达和淋巴结转移无明显相关.乳腺癌细胞浆Maspin蛋白与病理组织学分级、淋巴结转移及各项生物学因素无关.结论:细胞核Maspin蛋白绝大多数高表达于癌旁单纯性增生及正常乳腺上皮,细胞浆Maspin蛋白的高表达多出现在乳腺癌的早期及癌旁不典型增生,推测Maspin基因在乳腺癌的发生、发展中可能起一定的作用.     

α、β-微管蛋白在乳腺癌变不同阶段的表达及意义

背景与目的:紫杉烷类是治疗乳腺癌最重要的化疗药物之一,通过促进微管蛋白聚合,最终导致乳腺肿瘤细胞凋亡.然而紫杉烷类的耐药性常常限制了治疗效果,故揭示α、β-微管蛋白在乳腺癌变过程中表达水平的变化显得尤为重要.本文探讨乳腺非典型增生(atypical ductal hyperplasia,ADH)、导管内癌(ductal...     

端粒酶hTERT mRNA表达在乳腺癌进展中的意义及其与p53的相关性

目的 探讨端粒酶hTERT mRNA表达在人乳腺癌发生、发展中的意义,观察肿瘤抑制基因p53与hTERT mRNA表达的关系。方法 收集浸润性导管癌标本25例,导管原位癌标本18例,导管上皮不典型增生标本20例,导管上皮单纯性增生标本7例,癌旁正常乳腺组织标本12例。用原位杂交法检测hTERT mRNA表达,并用免疫组化方法检测乳腺导管癌的p53蛋白表达。结果 hTERT mRNA在癌旁正常乳腺组织、乳腺导管单纯性增生中未见表达;在导管不典型增生、导管原位癌、浸润性导管癌中的阳性率分别为25．0％、83．3％和88．0％。导管原位癌、浸润性导管癌组织hTERT mRNA表达明显高于癌旁正常乳腺组织、乳腺导管单纯性增生和导管不典型增生组织（P〈0．05）。hTERT mRNA表达与浸润性导管癌肿块大小及淋巴结转移与否无关（P〉0．05）。43例乳腺导管癌中,hTERT mRNA表达与p53蛋白表达呈正相关（r=0．5540,P〈0．01）。结论 端粒酶hTERT mRNA表达可能在乳腺导管癌的组织发生中起关键作用,半定量原位检测hTERT mRNA表达,可为导管上皮不典型增生与导管原位癌的鉴别诊断提供帮助。p53突变可能与乳腺导管癌hTERT基因转 录激活有关。     

CK5、CK8和BCRP在人乳腺病变组织中的表达及其意义

目的:探讨细胞角蛋白5(cytokeratin 5,CK5)、CK8和乳腺癌耐药蛋白(breast cancer resistance protein, BCRP)在乳腺上皮良、恶性增生病变中的表达及意义.方法:应用免疫组织化学法分别检测89例正常乳腺、乳腺增生、导管上皮非典型增生、导管原位癌和浸润性导管癌组织中CK5、CK8及BCRP的表达情况,分析CK5、CK8及BCRP的表达与乳腺病变组织分化程度之间的关系.结果: 在正常乳腺、乳腺增生、导管上皮非典型增生、导管原位癌和浸润性导管癌组织中CK5和CK8的阳性表达率逐渐下降,BCRP的阳性表达率则逐渐上升.CK5和CK8在乳腺良性增生组织(乳腺增生和导管上皮非典型增生)中的阳性表达率明显高于乳腺癌(导管原位癌和浸润性导管癌)组织(P＜0.01),BCRP在乳腺癌组织中的表达明显高于乳腺良性增生组织(P＜0.01).在乳腺浸润性导管癌中,CK5阳性表达主要集中在外层尚未受侵袭的基层细胞中,肿瘤细胞中没有表达或很少表达;CK8则主要在肿瘤细胞中表达,基层细胞中完全不表达;66.7%的浸润性导管癌患者呈CK5-/CK8+表型.结论:CK5、CK8和BCRP在不同乳腺病变组织中的表达不同,3者联合检测可能有助于乳腺病变的病理学诊断.     

乳腺导管内增生性病变的免疫表型分析

目的观察乳腺癌根治标本中导管内增生性病变的形态学及免疫表型特点和乳腺定向干细胞及其分化过程,探讨二者之间以及与浸润癌的关系。方法筛选出浸润性乳腺癌根治标本中有较多癌旁组织的病例43例,另筛选同期乳腺良性病变30例作为对照,选用CK5/6、CK34βE12、α-SMA、CK8、S-100蛋白等5种抗体做免疫组织化学染色。结果乳腺癌组43例中有37例伴有导管内增生性病变,其中普通型导管增生19例,柱状细胞变/增生15例,不典型导管增生7例,平坦上皮不典型性2例,导管原位癌27例;伴有2种及以上病变者19例,同时伴有4种病变者4例。对照组中普通型导管增生25例,柱状细胞变/增生5例,不典型导管增生1例。免疫组化染色显示,CK5/6在普通型导管增生中的腺系上皮细胞有明显表达,在柱状细胞变/增生、不典型导管增生、平坦上皮不典型性、导管原位癌和浸润性导管癌中不表达;CK34βE12在普通型导管增生中有大量表达,明显强于CK5/6,在1例低级导管原位癌中有灶性表达;S-100蛋白在普通型导管增生的腺系上皮细胞有明显的表达,而这些细胞不表达α-SMA,在肌上皮中的表达类似于α-SMA。在27例导管原位癌中,6例肌上皮细胞的表达弱于α-SMA,12例肌上皮细胞不表达S-100蛋白,而这些细胞对α-SMA明显表达。结论86%的浸润性乳腺癌伴有不同的导管内增生性病变,这些病变组织形态不同,免疫表型各异,但均与乳腺定向干细胞及其分化过程的免疫表型相吻合,可据此帮助诊断和鉴别诊断。     

C-erbB-2及P53蛋白在乳腺癌前病变中的表达及意义

目的探讨乳腺癌前病变C-erbB-2及P53蛋白表达对乳腺癌早期诊断的意义。方法应用免疫组化S-P法检测C-erbB-2及P53蛋白在不同程度乳腺导管上皮增生42例、乳头状瘤病86例及导管内癌28例、浸润性癌20例中的表达。如果C-erbB-2在轻度和重度导管上皮不典型增生及中、重度现头状瘤病均出现阳性或／和强附性表达.阳性串分别为五82％（2／11）、388％（7／18）和25.0％（7／28）、32.4％（12／37）.至导管内画表达阳性率达高峰,为50.0％（14／28）,而至浸润性癌阳性率反而降至35.0％（7／20）.P53蛋白在导管上皮增生及孔头状瘤病均无阳性表达,至导管内癌出现少许阳性表达,阳性牢3.5％（1／28）。而至浸润性癌达高峰,阳性率为25.0％（5／20）。结论C-erbB-2可用于筛选早期可疑乳腺癌,而P53蛋白则无早期诊断价值.     

FHIT在乳腺癌中的表达及其与临床病理指标的关系

目的研究FHIT在乳腺良、恶性疾病组织中的表达特点,分析其与乳腺浸润性导管癌临床病理指标之间的关系。方法采用免疫组化SP法检测42例浸润性导管癌、8例导管内癌、16例导管上皮不典型增生、30例乳腺病病理标本Fhit蛋白的表达水平,并对其在各组织中的表达水平进行病理学观察和半定量分析。结果 Fhit蛋白在乳腺病、导管上皮不典型增生、导管内癌及浸润性导管癌组织中的表达阳性率逐渐降低,比较差异有统计学意义（P〈0.01）。42例乳腺浸润性导管癌中有淋巴结转移组Fhit蛋白表达阳性率32.2%（8/25）,显著低于无淋巴结转移组58.8%（10/17）（P〈0.05）;临床Ⅰ期、Ⅱ期、Ⅲ期浸润性导管癌Fhit蛋白阳性表达率分别为90.0%、43.7%、12.5%,比较差异有统计学意义（P〈0.01）;Fhit蛋白的表达与Cerb-B2的表达呈负相关,γs=-0.357（P〈0.05）;Fhit蛋白的表达与p53的表达呈正相关,γs=0.411（P〈0.01）。Fhit蛋白的表达缺失与年龄、肿瘤的大小、组织学分级、ER、PR无明显相关性。结论 FHIT表达降低可能对乳腺癌的演化和进展具有一定作用;与浸润性导管癌的淋巴结转移、临床分期密切相关;与Cerb-B2、p53表达相关,可为乳腺癌的早期诊断、进一步治疗及预后判断提供理论依据。     

HPV16/18DNA和p53、RB、MCM7蛋白在乳腺癌中的表达及意义

目的:探讨HPV16/18DNA和p53、RB、MCM7蛋白在乳腺癌中的表达及意义.方法:用原位杂交和免疫组织化学EnVision法检测30例正常乳腺组织、30例乳腺腺病、30例乳腺不典型导管上皮增生、20例乳腺导管原位癌和68例乳腺癌组织标本中HPV16/18DNA和p53、RB、MCM7蛋白的表达.结果:乳腺癌组织中HPV16/18DNA的阳性率为58.8％,明显高于正常乳腺、乳腺腺病和乳腺不典型导管上皮增生组,差异有统计学意义(P＜0.05).在不典型导管上皮增生、导管原位癌和乳腺癌组织中HPV16/18DNA与p53和RB蛋白的表达均呈负相关(P＜0.05),而癌组中HPV 16/18DNA与MCM7蛋白表达呈正相关(r=0.750,P＜0.05).癌组中组织学G2、G3级,pTNM Ⅱ、Ⅲ期以及有淋巴结转移组中HPV16/18DNA和MCM7蛋白的阳性表达率均显著高于组织学G1级和pTNM Ⅰ期以及无淋巴结转移组(P＜0.05);与之相反,p53和RB蛋白的阳性表达率则显著降低(P＜0.05).结论:HPV16/18感染通过对p53、RB和MCM7蛋白表达调控的影响可能在高危型HPV感染后乳腺癌的发生、发展及转移进程中起到重要的作用.通过联合检测它们在乳腺癌及癌前病变中的表达以评价临床疾病进展和肿瘤生物学行为.     

乳腺癌组织中HIF-1α的表达水平及其与肿瘤血管生成相关性研究

目的:探讨缺氧诱导因子1α（hypoxia inducible factor 1α,HIF-1α）在乳腺正常组织、不典型增生、原位癌、浸润性癌组织中的表达水平,分析其与浸润性乳腺癌临床病理指标及肿瘤血管生成之间的关系。方法:收集20例正常乳腺组织、23例不典型增生、34例原位癌、80例浸润性乳腺癌组织标本,用免疫组化SP法检测各组中HIF-1α的表达,分析其在浸润性乳腺癌中的表达与肿瘤大小、腋窝淋巴结受累情况、TNM分期、组织学分级、激素受体等临床病理指标之间的关系。并用CD34标记肿瘤新生血管,分析HIF-1α表达对肿瘤血管生成的影响。结果:HIF-1α在正常乳腺组织中未见阳性表达,在乳腺不典型增生组织、原位癌组织、浸润性癌组织中表达阳性率分别为8.7%（2/23）、47.1%（16/34）及73.8%（59/80）,表达率依次增高,乳腺原位癌组织与不典型增生组织之间、乳腺浸润癌组织与原位癌组织之间差异具有统计学意义（P＜0.01）。在浸润性乳腺癌中,HIF-1α的表达在不同肿瘤直径、组织学分级及淋巴结转移分组中差异具有统计学意义（P均＜0.05）。浸润性导管癌HIF-1α阳性组MVD值（11.74±4.398）明显高于HIF-1α表达阴性组（9.093±2.856）,差异有统计学意义（P＜0.05）。HIF-1α表达与MVD值呈正相关性（r=0.633,P＜0.05）。结论:HIF-1α在浸润性乳腺癌组织中表达水平升高,其表达上调与乳腺癌新生血管生成密切相关。     

Low-grade and high-grade invasive ductal carcinomas of the breast follow divergent routes of progression

Low-grade invasive ductal carcinoma is almost diploid, and has frequent losses of chromosome 16q, which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia (FEA), atypical ductal hyperplasia (ADH), and lownuclear grade ductal carcinoma in situ (DCIS). The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma. This supports the linear progression model of breast cancer from FEA, through ADH, to lownuclear grade DCIS as non-obligate early events in low-grade IDC evolution. In contrast, high-grade carcinoma tends to aneuploidy with complex genetic alterations—most importantly, frequent gains at chromosome 16q. Frequent losses at chromosome 16q in low-grade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process. Therefore, low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.     

Low-Grade and High-Grade Invasive Ductal Carcinomas of the Breast Follow Divergent routes of Progression

Low-grade invasive ductal carcinoma is almost diploid,and has frequent losses of chromosome 16q,which is shared by other precancerous lesions of the mammary gland such as flat epithelial atypia(FEA),atypical ductal hyperplasia(ADH),and lownuclear grade ductal carcinoma in situ(DCIS).The genetic alterations accumulate in a stepwise fashion as the precancerous lesions progress to invasve ductal carcinoma.This supports the linear progression model of breast cancer from FEA,through ADH,to lownuclear grade DCIS as non-obligate early events in low-grade IDC evolution.In contrast,high-grade carcinoma tends to aneuploidy with complex genetic alterations-most importantly,frequent gains at chromosome 16q.Frequent losses at chromosome 16q in lowgrade IDC and gains in the same arm of the same chromosome in high-grade IDC imply that these lesions are two end outcomes of different disease processes and that they do not lie in the same continuum of a process.Therefore,low-grade and high-grade IDC are two distinct diseases with a divergent route of progression.     

The Immuno-fluorescence Quantity Analysis of α-Tubulin and γ-Tubulin Protein in Precancerous Lesion and Carcinoma of the Breast and Its Significance

OBJECTIVE To investigate the changes and values of the expression of α-tubulin and γ-tubulin in atypical ductal hyperplasia （ADH）, ductal carcinoma in situ （DCIS） and invasive ductal carcinoma （IDC） of the breast. The relationship between centrosome abnormalities and breast tumor development was further discussed. METHODS There were three groups including ADH, DCIS and IDC with 30 cases in each group. They were analyzed by immuno-fiuorescence quantity analysis. The expression levels of α-tubulin and γ-tubulin protein in these tissues were detected by flow cytometry immuno-fiuorescence analysis and compared with the results from normal tissues. Immunohistochemistry was also performed in this research. RESULTS The results showed significant differences of the average of the positive （FITC labeled） cells （P=0.000） among the four groups. The level of the IDC group was the highest, while normal breast tissue showed the lowest level. The results suggested that the expression levels of α-tubulin and γ-tubulin both increased as the grade of cellular proliferation and differentiation increased. The expressions showed significant differences among all the groups, except between the ADH and DCIS. There were no significant differences between α-tubulin and γ-tubulin expression in each group （P〈0.05）, as there was agreement in the immuno-fluorescence and immunohistochemical analysis for protein expression. CONCLUSION There is abnormal expression of centrosome tubulin as an early event in the development of breast tumor. Furthermore these aberrations may play a key role during oncogenesis and promote cellular transformation to malignancy. The immuno-fiuorescence quantitive analysis and immunohistochemistry can complement each other.     

ATF-3在乳腺癌中的表达及临床意义

目的:探讨激活转录因子-3(ATF-3)在乳腺癌组织中的表达及临床意义.方法:采用免疫组化法检测ATF-3在乳腺浸润性导管癌、导管原位癌和癌旁乳腺组织中的表达情况及其与乳腺癌临床病理特征间的关系.结果:ATF-3在乳腺浸润性导管癌、导管原位癌及癌旁乳腺组织中的阳性表达率分别为80.95%(85/105)、48.98%(24/49)和11.43%(12/105),乳腺浸润性导管癌组ATF-3的阳性表达率显著高于导管原位癌组和癌旁乳腺组织,导管原位癌组ATF-3的阳性表达率显著高于癌旁乳腺组织,差异均具有统计学意义(P<0.0167).ATF-3的表达与乳腺癌的组织学分级、淋巴结转移及临床分期相关,而与患者年龄及肿瘤大小无关.结论:ATF-3与乳腺癌的发生、发展、侵袭和转移有关,可能作为预测乳腺癌恶性程度和评估乳腺癌患者预后的重要指标.     

乳腺癌和乳腺导管内增生性病变JAG1基因甲基化的检测及临床意义

目的:探讨JAG1基因甲基化在乳腺浸润性导管癌发病中的作用。方法:采用MassARRAY方法对乳腺浸润性导管癌(IDC;n=75)、乳腺导管原位癌(DCIS;n=23)、乳腺非典型性导管增生症(ADH;n=20)以及乳腺普通型导管增生症(UDH;n=27)进行JAG1基因甲基化的定量检测。结果:JAG1基因启动区CpG_13、CpG_20.21.22、CpG_26位点在UDH组中的平均甲基化率高于ADH、DCIS、IDC组（P<0.05）。结论:在乳腺癌患者中JAG1(该基因的表达与乳腺癌细胞的生长、浸润、转移、预后有关)基因的部分位点呈现低甲基化改变。CpG_13、CpG_20.21.22、CpG_26位点的低甲基化改变与乳腺癌的形成具有相关性,可能该基因特异性CpG位点的低甲基化参与了乳腺良性病变向乳腺癌的发展演进过程。     

Expression of HIF-1α in breast cancer and precancerous lesions and the relationship to clinicopathological features简

Objective： The aim of this study was to observe the expressions and clinical significance of HIF-1a in breast cancer and precancerous lesions, and analyze the relationship between the expressions and clinicopathological features in breast cancer. Methods： We analyzed the HIF-1a expression in 128 cases of invasive ductal carcinomas, 146 precancerous lesions patients including 89 cases of ductal carcinoma in situ and 57 cases of atypical ductal hyperplasia. 53 cases of usual ductal hyperplasia breast tissues were selected as a control group. The specimens were evaluated for HIF-1a, estrogen receptor （ER） ＆ progesterone receptor （PR）, epidermal growth factor receptor type 2 （HER2/neu） and Ki-67. Immunoreactivity was semi-quantitatively evaluated in at least 1000 cells examined under the microscope at 40 x magnification and recorded as the percentage of positive tumor cells over the total number of cells examined in the same area. The percentage scores were subsequently categorized. The express of HIF-1a and their relationship with multiple biological parameters including ER ＆ PR, HER2/neu and Ki-67, the biomarkers levels of CA153, CA125 TSGF, and CEA in blood serum and nipple discharge, histological grade, region lymph node metastasis, distant metastasis and recurrence on files were also assessed. Results： Compared with usual ductal hyperplasia, the positive expression rate of HIF-1a in atypical ductal hyperplasia, ductal carcinoma in situ and invasive ductal carcinomas group was significantly increased （P 〈 0.01）. The positive rates of HIF-1a in invasive ductal carcinomas were 68.75%, which were significantly higher than that in ductal carcinoma in situ （43.8%）, atypical ductal hyperplasia （31.6%）, usual ductal hyperplasia （9.4%; X2 = 13.44, 22.27, 52.79, respectively, P 〈 0.01）. Statistical analysis showed that difference of abnormal expression rate of HIF-1a between ductal carcinoma in situ and usual ductal hyperplasia （X2 = 18.37, P = 0.00）, atypical ductal hyperplasia and usual ductal hyperplasia （x2 = 8.14, P = 0.00） was significant （P = 0.00）. However, no significant difference in the positive expression rate of HIF-1a was found between atypical ductal hyperplasia and ductal carcinoma in situ tissue （X2 = 2.19, P = 0.14）. There was a significantly difference in the mean HIF-1a frequency between ER ＆ PR positive invasive ductal carcinomas group and negative group, epidermal growth factor receptor type 2 （HER2/neu） positive and negative groups, Ki-67 proliferation index 〈 14% and 〉 14% groups, histological grade （I ＋ II） and grade III invasive ductal carcinomas groups, with lymph node metastasis, distant metastasis and recurrence groups （P 〈 0.05） and without groups （P 〈 0.05）. However, there was not difference in the mean HIF-1a between age （〈 50 years vs 〉 50 years）, tumor diameter （〈 2 cm vs 〉 2 cm; P 〉 0.05）. The nipple discharge and serum levels of CA153, TSGF, CA125 and CEA in invasive ductal carcinomas HIF-1a positive patients were significantly higher than those in the negative patients （P 〈 0.05）. Conclusion： In breast cancer, HIF-1a expressibn was abnormally increased. The aberration of HIF-1a may play a key role during oncogenesis （atypical ductal hyperplasia or ductal carcinoma in situ） and promote breast cellular transformation into malignancy, a finding useful for further understanding of tumorigenesis. The abnormal expression of HIF-1a may be as an early event in the development of breast tumor. The over-expression of HIF-1a might be important biological markers for invasion, metastasis and recurrence of breast cancer.     

乳腺导管原位癌与浸润性导管癌染色体微卫星杂合性缺失的比较

目的:研究乳腺导管原位癌与浸润性导管癌染色体3p区域微卫星杂合性缺失(loss of heterozygosity,LOH)的发生情况.方法:选取本院2005年9月至2009年2月手术切除石蜡包埋的乳腺癌组织切块43例,应用激光显微切割技术留取组织中乳腺浸润性导管癌(invasive ductal type carci...     

Diagnosis of ductal carcinoma in situ (DCIS) and intraductal papilloma using fluorescence in Situ Hybridization (FISH) analysis

BACKGROUND: It is often difficult to pre-operatively diagnose ductal carcinoma in situ (DCIS)or intraductal papilloma (IDP). Current reports show that breast cancer frequently has numerical aberrations of chromosomes 1, 11 and 17. We investigated whether fluorescence in situ hybridization (FISH) analysis using three centromere-specific probes for chromosomes 1, 11 and 17 was feasible for diagnosing intraductal breast lesions. METHODS: Fine-needle aspiration specimens from 102 breast lesions including DCIS (10), invasive ductal carcinoma (IDC) (78), IDP (7), fibroadenoma (6) and mastopathy (1) were examined for numerical aberrations on chromosomes 1, 11, 17 using FISH. If over 15% of all cells showed one signal, the sample was judged monosomic. If over 20% of cells showed three or more signals, it was considered polysomic. If the specimen had an aberration of at least one chromosome, it was judged positive. RESULTS: Nine of 10 DCISs showed numerical aberrations of at least one chromosome whereas 65 of 78 IDCs and 2 of 14 benign lesions (containing 7 IDPs of which one case was positive) showed numerical aberrations on these chromosomes. The proportion of positive results was highest with DCIS. Moreover 6 out of 7 DCISs showed an aberration of all three chromosomes simultaneously and one case showed an aberration of two chromosomes. All aberrations in case of DCIS were polysomic while two benign lesions and 15 IDCs showed a monosomic pattern. CONCLUSION: FISH may enable more accurate diagnosis of intraductal breast lesions.     

乳腺浸润性导管癌中MGMT、XRCC1蛋白表达及意义

目的 探讨乳腺非特殊型浸润性导管癌中MGMT和XRCC1的表达及临床意义.方法 采用S-P免疫组化法检测72例乳腺非特殊型浸润性导管癌石蜡标本、30例乳腺良性病变石蜡标本中MGMT和XRCC1蛋白的表达,分析其表达与临床因素的相关性.结果 72例乳腺癌组织中MGMT阳性表达率为70.8%,低于良性病变组织表达率90.0%（P＜0.05）,且其表达与非特殊型浸润性导管癌的病理分化程度、ER及p53表达相关（P＜0.05）.XRCC1阳性表达率为52.8%,低于良性病变组织表达率83.3%（P＜0.05）,且其表达与非特殊型浸润性导管癌病理分化程度相关（P＜0.05）.结论 DNA修复基因MGMT及XRCC1是临床评估乳腺癌恶性程度、判断预后及制定治疗策略的重要病理指标.