乳腺癌中Livin基因及蛋白表达与细胞凋亡、增殖的关系

目的探讨Livin在乳腺癌表达及其与caspase-3蛋白表达和细胞增殖的相互关系。方法采用SP法免疫组化和原位杂交技术检测Livin在正常乳腺组织（14例）、乳腺增生性病变（14例）、乳腺非浸润性癌（20例）和乳腺浸润性癌组织（52例）中Livin mRNA和其蛋白的表达以及caspase-3、Ki-67在乳腺癌组织中的表达。结果Livin蛋白和mRNA在正常乳腺组织、乳腺增生性病变、乳腺非浸润性癌和乳腺浸润性癌组织中阳性率分别为（7．1％、7．1％）、（28．6％、28．6％）、（65．0％、70．0％）、（73．1％、75．0％），差异有统计学意义（P〈0．01）。Livin蛋白与mRNA表达之间差异无统计学意义（P〉0．05）。Livin表达与临床分期、淋巴结转移和年龄有关（P〈0．05），与肿瘤大小和组织学分级无关。Livin蛋白与caspase-3的在乳腺癌表达呈负相关（P〈0．01）。Livin蛋白表达阳性的乳腺癌Ki-67增殖指数（47．32％±22．34％）明显高于Livin蛋白表达阴性的乳腺癌Ki．67增殖指数（18．01％±23．34％）（P〈0．01）。结论Livin基因及蛋白在乳腺癌中表达上调，提示在乳腺癌发生、发展中起重要作用，可作为乳腺癌新的分子标记物，可能成为乳腺癌诱导凋亡治疗的新靶点。Livin蛋白通过与执行型caspase-3结合，抑制其活性，从而阻止细胞凋亡。Livin不仅参与细胞凋亡的调控，还促进了细胞增殖及肿瘤的发生、发展。     

乳腺癌组织中VEGF的表达及临床意义

目的：探讨乳腺癌组织中血管内皮生长因子（VEGF）的表达及其临床病理意义。方法：采用快捷免疫组化MaxVisionTM法，对68例乳腺癌组织和22例乳腺良性病变组织中VEGF的表达进行检测，结合临床及病理形态学资料进行统计分析。结果：VEGF的阳性表达率为乳腺癌42．6，乳腺良性病变组织中为5．02，两者比较，差异均有统计学意义（均P〈0．05）。VEGF的表达与乳腺癌患者年龄、肿瘤大小及组织学分型无关，而与乳腺癌组织学分级、临床分期和腋窝淋巴结转移有关（P〈0．05）。结论：VEGF可能与乳腺癌的进展、转移及预后有关，作为独立的指标对判定预后和制定治疗方案具有参考意义。     

乳腺导管内增生性病变中ER、Ki-67和cyclin D1的表达

目的 探讨ER、Ki-67和cyclin D1在乳腺导管内增生性病变中的表达及意义。方法 采用免疫组化和免疫荧光双标记法对56例乳腺导管内增生性病变进行ER、 Ki-67和cyclin D1染色标记。结果 正常乳腺组织中仅有散在的少数上皮细胞呈ER阳性表达。在普通型导管增生（usual ductal hyperplasia，UDH）中ER表达比正常乳腺组织增加，但ER阳性细胞呈不连续分布，阳性细胞间有较多的阴性细胞。非典型性导管增生（atypical ductal hyperplasia，ADH）和低级别原位导管癌（ductal carcinoma in situ，DCIS）中ER表达比UDH明显增加（P〈0．05），ER阳性细胞呈连续的片状分布，阳性细胞间较少或没有ER阴性细胞。ADH和低级别DCIS中ER表达较高级DCIS显著（P〈0．01）。DCIS中Ki-67和cyclin D1表达高于UDH（P〈0．05），并与UDH、ADH和DCIS的组织学分组呈正相关（r=0．352，P〈0．05和r=0．390，P〈0．05）。正常乳腺组织中上皮细胞内无ER和Ki-67同时表达。在UDH中有极少数上皮细胞ER和Ki-67同时表达，而在ADH和DCIS中ER和 Ki-67同时表达的细胞明显增加。结论 从正常乳腺组织到UDH、ADH、低级DCIS的恶性转化过程中伴有ER表达的逐渐增高。ER过度表达及ER和Ki-67在上皮细胞内同时表达可能是某些乳腺癌发生过程中的早期事件。     

乳腺癌中同源异型盒基因(HOX)A5表达的研究

目的研究乳腺癌组织中同源异型盒基因（HOX）A5mRNA和蛋白表达,并分析其与乳腺癌临床病理参数间的相关性,以探讨HOXA5基因在乳腺癌发生、发展及转移中的作用。方法运用TaqMan实时荧光定量逆转录聚合酶链反应（Real-time RT-PCR）技术检测60例乳腺癌（其中54例浸润性导管癌）和24例乳腺良性病变中HOXA5 mRNA表达,免疫组织化学SP法检测HOXA5蛋白表达。统计学办法分析HOXA5攮因表达与乳腺癌临床病理参数间的关系。结果（1）乳腺癌中HOXA5 mRNA相对表达量为0．73～193．07,均值为20．85;乳腺良性病变中相对表达量为5．42～81.91,均值为30．94。乳腺癌HOXA5 mRNA表达明显低于良性乳腺病变（P〈0．01）。（2）乳腺癌中HOXA5蛋白表达减少或消失。（3）淋巴结转移阳性乳腺癌病例HOXA5 mRNA表达明显低于转移阴性组,两者间差异有统计学意义（P〈0．05）。HOXA5蛋白在淋巴结转移阳性和阴性乳腺癌中的表达差异具有显著性（P〈0．01）。淋巴结转移阳性的乳腺癌中HOXA5蛋白主要呈弱阳性表达或表达缺失,在淋巴结转移阴性的乳腺癌中主要呈中度至强阳性表达。（4）HOXA5 mRNA和蛋白表达与乳腺癌患者年龄、肿瘤大小、临床分期、组织学分型、浸润性导管癌分级等其他临床病理学参数间未见相关性（P〉0．05）。结论HOXA5基因表达异常可能与乳腺癌有关。HOXA5基因表达抑制可能与乳腺癌淋巴结转移有关。     

RUNX3基因表达对判断人乳腺癌预后的价值

目的探讨乳腺癌组织中RUNX3基因的表达及其与乳腺癌生物学特征和预后的关系。方法采用免疫组化SP法检测RUNX3蛋白在88例乳腺癌、40例乳腺纤维腺瘤和40例乳腺增生病组织中的表达。结果（1）RUNX3在乳腺癌中的阳性表达率为35．23％，明显低于在乳腺纤维腺瘤（85％）及乳腺增生病（87．5％）组织中的表达率，差异具有统计学意义（P〈0．05）。（2）RUNX3蛋白表达与乳腺癌有无浸润、临床分期、淋巴结转移、ER、PR表达相关，而与病人的年龄、肿瘤类型、病理分级无关。（3）RUNX3表达阳性者的：生存率高于表达阴性者的生存率（P〈0．05）。RUNX3阳性表达者，术后生存时间长。结论（1）乳腺癌组织中RUNX3蛋白表达降低，证明RUNX3基因可能作为一个抑癌基因参与乳腺癌的发生。（2）随着乳腺癌的临床进展，RUNX3表达下降。（3）RUNX3在乳腺癌中的表达对评价患者的预后有一定价值。     

实时荧光定量PCR检测乳腺癌SOCS2基因表达

目的检测乳腺良恶性组织中细胞因子信号转导抑制因子（supressors of cytokine signaling，SOCS2）的mRNA表达及其临床病理意义。方法以18SrRNA为内j对照采用实时荧光定量PCR法，定量测定新鲜乳腺癌组织、癌旁组织和乳腺良性增生组织中。SOCS2 mRNA的表达并分析其与临床病理指标的关系。结果各组阳性率：乳腺癌35.00％（14／40）、癌旁乳腺组织100％（15／15）和乳腺良性增生组织81.25％（13／16），其表达之间的差异具有统计学意义（P〈0．05）；乳腺癌组织的SOCS2表达水平与TNM分期和淋巴结转移呈明显的相关性（P〈0，05）。结论SOCS2在乳腺癌中的表达可能提示患者具有较好的预后。     

妊娠滋养细胞肿瘤组织中cyclin D1、Rb蛋白产物的表达

目的：探讨增殖相关基因cyclin D1、Rb在妊娠滋养细胞肿瘤中的表达变化。方法：采用免疫组化S－P法,检测20例葡萄胎、15例侵蚀性葡萄胎、15例绒毛膜癌组织中两种基因蛋白产物的表达。结果：在恶性滋养细胞肿瘤组织中,cyclinD1的阳性表达率随临床期别的增高呈递增趋势,而Rb呈递减趋势,二者在Ⅲ期的阳性表达率与Ⅰ期及Ⅱ期相比差异均具有显著性（P＜0．05）;化疗可降低cyclinD1在恶性滋养细胞肿瘤中的阳性表达,而对Rb无影响。结论：cyclin D1的过表达,Rb的缺失在妊娠滋养细胞肿瘤的发展中可能有重要的生物学意义。     

凋亡调节蛋白FasL，Fas和P53在乳腺癌的表达及其意义

目的 观察人乳腺癌组织、癌旁相对正常乳腺组织中凋亡调节蛋白FasL，Fas、P53的表达，探讨FasL，Fas及P53与乳腺癌发生发展的关系。方法 收集手术切除的人乳腺癌组织和癌周相对正常乳腺组织，用免疫组织化学方法对21例乳腺癌标本进行检测。结果 乳腺癌组织中Fas蛋白表达的阳性率明显低于癌周正常乳腺组织（P〈0．01），有淋巴结转移者明显低于无淋巴结转移者（P〈0．05）。乳腺癌组织中FasL、P53蛋白表达的阳性率均明显高于癌周正常乳腺组织（P〈0．01），有淋巴结转移者明显高于无淋巴结转移者（P〈0．05）。结论 乳腺癌组织中Fas／FasL表达异常使肿瘤逃脱机体自身免疫攻击，促使肿瘤的发生发展，对预测乳腺癌的预后有重要参考价值。突变型P53在乳腺癌中过表达，可能抑制肿瘤凋亡的发生，促进肿瘤生长。     

SBP1和Caspase-3在人乳腺癌组织中的表达及意义

目的观察人乳腺癌组织中硒结合蛋白1（SBPl）和凋亡调节蛋白（Caspase-3）的表达,探讨SBPl和Cas-pase-3在乳腺癌发生、发展过程中的作用及其相互关系。方法用免疫组织化学ABC法检测乳腺癌中SBPl和Caspase-3的表达水平,并与癌旁相对正常组织、乳腺良性病变组织进行比较分析。结果SBP1、Caspase．3在癌旁相对正常乳腺组织中的阳性表达率为100％、86．6％;在乳腺良性病变组织的阳性表达率为93.3％、73．3％;在乳腺癌组织的阳性表达率为82．1％、57．1％。乳腺癌组织中SBP1和Caspase．3的表达水平均明显低于癌旁相对正常组织和乳腺良性病变组织。乳腺癌组织中SBPl与Caspase-3的表达呈正相关。结论乳腺癌组织中SBP1和Caspase-3的表达下调,提示SBPl可能通过促进肿瘤细胞的凋亡来抑制肿瘤的增殖,为进一步对硒诱导SBPl治疗乳腺癌的作用研究提供基础。     

乳腺浸润性导管癌中p57kip2、cyclin D1和cyclin E的表达及意义

目的探讨p57kip2、cyclin D1及cyclin E蛋白在乳腺癌发生、发展中作用.方法用免疫组化S-P法检测64例乳腺浸润性导管癌(invasive ductal carcinoma,IDC)、15例乳腺导管原位癌(ductal carcinoma in situ,DCIS)和15例癌旁正常乳腺组织中p57kip2、cyclin D1和cyclin E蛋白的表达情况.结果p57kip2、cyclin D1和cyclin E蛋白在IDC的阳性率与在乳腺不同组织之间相比,cyclin D1、cyclin E蛋白在DCIS的阳性率与癌旁正常乳腺组织之间相比差异均有显著性(P≤0.05,P＜0.01).在IDC中,三者表达均与腋窝淋巴结转移有关(P≤0.05,P＜0.01),cyclin D1蛋白的表达与组织学分级有关(P＜0.01),cyclinE蛋白的表达与肿块大小有关(P＜0.01);p57kip2与cyclin D1之间、p57kip2与cyclin E之间的表达均呈负相关(P＜0.01)、cyclinD1与cyclin E之间的表达呈正相关(P＜0.01).结论p57kip2蛋白低表达、cyclin D1和cyclin E蛋白高表达可能是乳腺组织恶性转变以及乳腺癌发生淋巴结转移的重要生物学标志,cyclin D1和cyclin E蛋白异常表达是乳腺癌发生的早期事件.联合检测p57kip2、cyclin D1及cyclin E蛋白对预测乳腺癌淋巴结转移有重要意义.     

cyclinD1,Rb基因蛋白在乳腺癌中的表达

目的：探讨ｃｙｃｌｉｎＤ１基因及Ｒｂ基因的表达与乳腺癌发生发展的关系。方法：应用ＡＢＣ免疫组化法检测２４例良性乳腺组织及５８例乳腺癌中ｃｙｃｌｉｎＤ１及Ｒｂ蛋白表达。结果：乳腺癌中ｃｙｃｌｉｎＤ１过表达阳性率５８．６２％（３４／５８）显著高于良性乳腺组织中的１６．６７％（４／２４），Ｐ＜０．０５。ｃｙｃｌｉｎＤ１过表达出现于导管原位癌并持续于浸润、转移等进展过程中，与年龄、肿瘤大小、组织学类型及淋巴结状态无相关性，但与组织学分级负相关。乳腺癌中Ｒｂ蛋白表达阳性率为３６．２％（２１／５８），显著低于良性乳腺组织的７５％（１８／２４），Ｐ＜０．０５；未见Ｒｂ失表达与临床病理参数间存在相关性，Ｒｂ表达与ｃｙｃｌｉｎＤ１过表达呈正相关。结论：ｃｙｃｌｉｎＤ１过表达及Ｒｂ失表达是乳腺癌发生中的重要事件且前者是一早期分子事件；ｃｙｃｌｉｎＤ１过表达发挥作用可能部分依赖于Ｒｂ蛋白的存在；提示细胞周期调控异常参与乳腺癌的发生。     

Correlation of cyclin D1 and Rb gene expression with apoptosis in invasive breast cancer.

BACKGROUND: In vitro studies have shown that amplification and overexpression of the cyclin D1 gene can accelerate the progress of cells through the G1 phase. Therefore, cyclin D1 may have an apoptosis inhibiting effect. The retinoblastoma (Rb) gene was shown recently to be an important regulator of apoptosis. AIMS: To evaluate whether expression of the cyclin D1 and Rb genes correlated with apoptotic counts in a group of 97 invasive breast cancers. METHODS: Expression of the cyclin D1 and Rb genes was detected by standard immunnohistochemistry using paraffin wax embedded sections. Apoptotic cells were counted according to a strict protocol, in 10 fields of vision systematically spread over the most poorly differentiated area of the tumour, at a magnification of x630. Apoptotic cells counts were expressed as apoptotic cells/mm2. RESULTS: Cyclin D1 overexpression was found in 49% of cases. Loss of Rb expression was found in 44% of cases, and occurred particularly in poorly differentiated tumours. Cyclin D1 and Rb expression showed a positive correlation (p = 0.003). Apoptotic counts varied from 1 to 62/mm2. There were no significant correlations between cyclin D1 overexpression and apoptotic counts in the total group or in the retinoblastoma protein (pRb) positive tumours. Loss of Rb expression also showed no correlation with apoptotic counts. CONCLUSIONS: Cyclin D1 is frequently overexpressed in pRb positive tumours, but no evidence has been found for an anti-apoptotic effect of cyclin D1 overexpression or Rb expression in invasive breast cancer.     

Cyclin D1, retinoblastoma, p53, and Her2/neu protein expression in preinvasive breast pathologies: correlation with vascularity.

OBJECTIVES: Preinvasive breast pathologies show a degree of vascularization that correlates with risk of invasion. Recently, numerous oncogenes and tumor suppressor genes have been shown to regulate neovascularization. Therefore, we examined archival tissues of preinvasive breast pathologies by immunohistochemistry for alterations in the expression of four proteins, cyclin D1, retinoblastoma (Rb), p53, and Her2/neu, known to be important in breast tumorgenesis, and correlated these data with tissue vascularity. METHODS: Vascularity was determined by immunologic detection of von Willebrand factor. For carcinoma in situ (CIS) both stromal vascularity (MVD) and vascular cuffing (MCD) were determined. RESULTS: We found that cyclin D1 expression was increased in usual hyperplasia (11% of cases). Atypical hyperplasia, noncomedo CIS and comedo CIS were positive in 43, 49, and 57% of cases, respectively. Changes in Rb and p53 were rare in hyperplasia but occurred in 8 and 10% of CIS, respectively. Her2/neu protein was identified rarely in atypical hyperplasia and in both noncomedo and comedo ductal CIS. Neither Rb nor Her2/neu expression correlated with vascularity. p53 immunoreactivity correlated positively with both MCD and MVD. Cyclin D1 was negatively associated with MVD. CONCLUSION: These data suggest that p53 and cyclin D1 proteins may regulate the microvessel density of preinvasive breast pathologies.     

Expression of p21Waf1, p27Kip1 and cyclin D1 proteins in breast ductal carcinoma in situ: Relation with clinicopathologic characteristics and with p53 expression and estrogen receptor status

p21Waf1 (p21), p27Kip1 (p27) and cyclin D1 have recently been reported as useful prognostic markers for patients with breast carcinoma. However, studies on these cell cycle regulators in ductal carcinoma in situ (DCIS) have been extremely limited. Therefore, we studied the immunohistochemical expression of p21, p27 and cyclin D1 proteins in 49 DCIS cases and compared the findings with the clinicopathologic parameters (age, tumor size, gross type, histologic type, histologic grade, necrosis and mitotic index), p53 and estrogen receptor (ER) status. A significant correlation was found between positive p21 immunoreactivity (67.3% of the cases) and well-differentiated histologic grade, non-comedo type, ER-positive and p53-negative (p53-) status. DCIS with p21+/p53- is likely to be the non-comedo type. The overexpression of cyclin D1 (59.2% of the cases) correlated positively with the ER expression (P = 0.001). The p27 protein expression (46.9% of the cases) correlated with the cyclin D1 immunopositivity (P = 0.0003) and ER expression (P = 0.005). No significant associations were seen in the p27 or cyclin D1 expression and other clinicopathologic parameters. Our results suggest that p21 might be more related to the useful biologic markers in DCIS than p27 or cyclin D1. The significant positive association between p21, p27 or cyclin D1 and ER status, and close association of p27 and cyclin D1 expression might be implicated in the tumor biology of DCIS.     

Differential expression of cyclin D1 in breast papillary carcinomas and benign papillomas: an immunohistochemical study

OBJECTIVES: Distinguishing intraductal papilloma from papillary carcinoma of the breast can be difficult using histologic criteria. Since cyclin D1, a G1 cell-cycle regulatory protein, is detectable immunohistochemically in a subset of breast carcinomas but not in benign breast tissues, we hypothesized that cyclin D1 immunoreactivity may be a marker for identifying papillary carcinoma. METHODS: Using an immunohistochemical method, we assessed for cyclin D1 expression in 8 breast papillomas and 6 papillary carcinomas, all of which were formalin fixed, routinely processed, and paraffin embedded. Cyclin D1 positivity also was compared with the overall proliferation rate, which was assessed by using the proliferation marker Ki-67. In each case, a 200-cell count was performed to obtain the percentage of cells positive for these 2 markers. RESULTS: The percentage of cyclin D1-positive cells was significantly higher in papillary carcinomas (89%+/-18%; range, 53%-98%) than in papillomas (8%+/-7%; range, 0%-19%). This difference was highly statistically significant (P < .0001). Although the difference in Ki-67 positivity between these 2 groups was also statistically significant (P = .01), separation of papillary carcinomas and papillomas by Ki-67 immunoreactivity was less clear because of overlapping values between groups: 13% +/-6%; range, 9% to 23% for papillary carcinomas versus 8%+/-2%; range, 6% to 12% for papillomas. CONCLUSIONS: These results support the notion that cyclin D1 is a useful marker for distinguishing breast papillomas from papillary carcinomas. The marker Ki-67 is also helpful, but is less useful than cyclin D1, owing to the overlap in Ki-67 results in papillomas and papillary carcinomas.     

Mean nuclear area and metallothionein expression in ductal breast tumors: correlation with estrogen receptor status.

Breast carcinoma is the most common malignancy in women. Estrogen is an important growth factor for breast tumor that plays an important role in regulating the proliferation and differentiation of normal and malignant mammary epithelial cells. Nuclear morphometry and metallothioneins (MTs) are indicators of proliferation that have been used as predictors of prognosis in many tumors. The present study aimed to study mean nuclear area (MNA) and MT; estrogen receptor (ER) expression in fibroadenoma (FA), ductal carcinoma in situ (DCIS), and infiltrating ductal carcinoma (IDC) of the breast. Also MNA and MT expression will be correlated with histologic grade and ER status in breast carcinoma. Breast tissues from 18 patients with FA, 10 patients with DCIS, and 40 patients with IDC were used in this study. MNA and MT expression; as proliferation markers; were investigated and correlated with ER status. All cases of FA, 7 out of 10 cases (70%) of DCIS and 23 out of 40 cases (57.5%) of IDC were positive for ER. MNA of cancer cells was significantly larger than that of normal and benign breast tissue. A significant direct correlation was found between MNA and histologic grades. MNA of ER-negative carcinomas was significantly larger than that of ER-positive tumors. In normal and benign breast tissue, myoepithelial cells consistently expressed the MT protein. Four out of 10 DCIS cases (40%) and 24 out of 40 cases of IDC cases (60%) were positively stained for MT. MT positivity was directly correlated with histologic grade of IDC. There was a highly significant inverse correlation between MT and ER overexpression. From this study, it is concluded that in invasive ductal carcinoma of the breast, the large MNA and MT overexpression are correlated with histologic grades and ER negativity. Therefore, large MNA and MT overexpression may be possible important indicators for more aggressive and less differentiated breast carcinoma.     

Expression of cyclin D1 and c-Ki-ras gene product in human epithelial ovarian tumors

The expression of cyclin Dl gene product in human ovarian tumors was studied. We found that cyclin D1 is expressed at high levels in several ovarian cancer cell lines. Immunohistochemical study also showed that a significant proportion of primary ovarian tumor tissues overexpressed cyclin D1 gene product. Clear nuclear staining of cyclin Dl protein was detected in 28% of the cases. We also characterized the expression of c-Ki-ras gene product in ovarian cancer cell lines and tumor tissues. Amplification or overexpression of this protooncogene has been reported in ovarian tumors from Taiwan. These results show that c-Ki-ras is strongly expressed in PA-1 and NIH: OVCAR-3 cells in which cyclin D1 also expressed at high levels. Specific cytoplasmic staining of c-Ki-ras protein was detected in 11 tumors (52%). Statistical analyses show a strong positive correlation between cyclin D1 and c-Ki-ras immunoexpression. Thus, these data support the ideas that cyclin D1 may be involved in the pathogenesis of ovarian cancer, and coactivation of cyclin D1 and c-Ki-ras gene expression may represent one of the major pathways that lead to the development of ovarian cancer in Taiwan.     

Cyclin D1 expression in invasive breast cancer. Correlations and prognostic value.

Cyclin D1 overexpression, detected by standard immunohistochemistry, was correlated with other prognostic variables and its prognostic value was evaluated in a group of 148 invasive breast cancers with long-term follow-up. Overexpression of cyclin D1 (59% of cases) was negatively correlated (chi 2 test) with histological grade (P = 0.0001), mean nuclear area (P = 0.004), mean nuclear volume (P = 0.02), and mitotic activity (P = 0.03) and positively correlated with estrogen receptor (P = 0.0001). There was a strong correlation between cyclin D1 overexpression and histological type (P = 0.0001). Positive cyclin D1 staining was seen in 11 of 13 tubular carcinomas, 3 of 3 mucinous carcinomas, 4 of 4 invasive cribriform carcinomas, and 17 of 20 lobular carcinomas. Of 102 ductal cancers, 52 were positive, and all 6 medullary carcinomas were negative. There were no significant correlations with lymph node status, tumor size, or DNA ploidy. In survival analysis, cyclin D1 overexpression did not provide significant univariate or multivariate prognostic value. In conclusion, cyclin D1 is mainly overexpressed in the well differentiated and lobular types of invasive breast cancer and is strongly associated with estrogen receptor positivity. It is negatively correlated with the proliferation marker mitoses count and with the differentiation markers nuclear area and nuclear volume. However, cyclin D1 overexpression does not seem to have prognostic value in invasive breast cancer when no adjuvant treatment is given.     

免疫组织化学标记物在乳腺细针吸取细胞学鉴别诊断中的意义

目的探讨免疫标记物对鉴别乳腺细针吸取细胞学（FNAC）良性病变和癌的意义。方法收集135例有随访资料、活检和组织病理学诊断对照的乳腺FNAC资料：良性病变88例,包括非增生性病变43例和增生性病变45例;乳腺癌47例,对其FNAC涂片和相应的石蜡切片作细胞周期蛋白（cyclin）D1、c—erbB-2、Ki-67、p21^CIP1/WAF1（简称p21）和34βE12的免疫组织化学APAAP和ABC法检测。利用SPSS11．5软件进行分析。结果（1）以上各标记物在良性非增生性和增生性病变中的标记差异无统计学意义。（2）以上各标记物在良、恶性病变中的标记差异均有统计学意义（P〈0．001）。多因素的logistic回归分析显示最有意义的组合标记物为cyclinD1（P〈0．001）、34βE12（P〈0．001）和c—erbB-2（P=0．003）．cyclinD1、c—erbB-2阳性和34βE12阴性提示为癌,其组合诊断的敏感性和特异性最高。组合标记物共同判断,cyclinD1和34βE12任一判断为癌,诊断的敏感性和特异性分别为95．7％和94．3％;这三个标记物任一判断为癌,诊断的敏感性进一步上升至97．9％,特异性下降至92．0％;这三个标记物任两个共同判断为癌,诊断的敏感性为72．3％,特异性为100．0％。（3）在癌组中,根据Robinson细胞学分级把癌分为3级,cyclinD1、34βE12和p21在各级癌中的表达差异不大,而c—erbB-2和Ki-67在1级癌的阳性表达率最低,仅为40．0％和33．3％,在3级癌中阳性表达率最高。组合cyclinD1和34βE12,cyclinD1和34βE12,任一判断为癌,1级和2级癌的检出率为93．3％和96．2％。结论所检测的免疫标记物对良、恶性病变的鉴别诊断价值较大,组合cyclinD1、34βE12和c—erbB-2可最有效地提高癌的诊断敏感性和特异性。对鉴别分化好的乳腺癌和乳腺良性病变,最有效的组合为cyclinD1和34βE12。     

Expression characteristics of prostate-derived Ets factor support a role in breast and prostate cancer progression

The purpose of this study was to understand the characteristics of prostate-derived Ets factor (PDEF) protein expression in breast and prostate cancer progression. A polyclonal antibody specific to PDEF was raised and reacted with tissue microarrays consisting of benign breast, in situ ductal, invasive ductal, and invasive lobular breast carcinomas. The antibody was also reacted with tissue microarrays, including benign prostate, prostate intraepithelial neoplasias (PINs), and prostate carcinomas. Increased expression of PDEF was identified in 18%, 50%, 46%, and 51% of benign breast tissues, intraductal, invasive ductal, and invasive lobular carcinomas, respectively. Importantly, in matched samples of benign breast vs tumor, 90% showed higher expression of PDEF in the tumor tissue. Moreover, in invasive breast carcinomas, increased PDEF expression tended to correlate with Her2/neu overexpression. Increased expression of PDEF was also found in 27%, 33%, and 40% of benign prostate tissues, PIN samples, and prostate adenocarcinomas, respectively. Again, in matching samples of cancer vs benign and cancer vs PIN, 68% and 70%, respectively, showed increased expression in the malignant tissue. Moreover, PDEF was found to be more highly expressed in tumors with intermediate or high Gleason score compared with low-grade tumors (P < .01). In addition, R1881 treatment induced PDEF expression in the LNCaP prostate tumor cell line, suggesting regulation of PDEF by androgens in vivo. Together, these results for the first time show frequent increased expression of PDEF protein in breast and prostate tumors and support a role for PDEF in breast and prostate cancer progression.