乳腺浸润性导管癌中N-cadherin mRNA及蛋白的表达与预后分析

目的 探讨N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的表达及其临床意义.方法 采用原位杂交技术和免疫组化SP法检测70例乳腺浸润性导管癌中N-cadherin mRNA及蛋白表达,以30例乳腺不典型导管增生为对照组.结果 乳腺浸润性导管癌中N-cadherin mRNA及蛋白阳性率分别为61.4%(43/70)、68.6%(48/70),乳腺不典型导管增生中N-cadherin mRNA及蛋白阳性率分别为3.3%(1/30)、6.7%(2/30),差异有统计学意义(P<0.01);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达与淋巴结转移、TNM分期以及ER、PR表达有关,差异有统计学意义(P均<0.01);与患者年龄、肿瘤大小和组织学分级无关(P均>0.05);N-cadherin mRNA及蛋白在乳腺浸润性导管癌中表达呈正相关(rs=0.73,P<0.01);N-cadherin mRNA阳性患者生存率明显低于阴性患者,差异有统计学意义(P<0.01).结论 N-cadherin mRNA及蛋白在乳腺浸润性导管癌中的过表达提示其对乳腺癌发生、发展、浸润及转移起重要作用,并提示患者预后不良.     

E-cadherin阴性乳腺小管小叶癌5例临床病理分析

目的探讨E-cadherin阴性乳腺小管小叶癌的临床病理学特征、诊断及鉴别诊断。方法收集5例乳腺小管小叶癌,采用免疫组化EnVision两步法检测E-cadherin、p120、β-catenin、ER、PR、HER-2和Ki-67的表达,并结合临床病理学信息进行回顾性分析。结果浸润性小叶癌占同期浸润性癌的3.4%(143/4 175),其中5例为乳腺小管小叶癌(3.5%,5/143),其组织学形态均形成管腔样的结构,管腔较小、由单层腺上皮围绕而成,癌细胞间的黏附性较差,可围绕正常导管呈靶环样排列,可与浸润性小叶癌和浸润性导管癌共存;免疫组化染色显示E-cadherin缺失,p120呈胞质阳性或胞质胞膜阳性,β-catenin缺失或胞质弱阳性,ER均阳性,PR为50%阳性,HER-2评分为1+,Ki-67增殖指数均10%。结论 E-cadherin阴性的乳腺小管小叶癌形态类似E-cadherin阳性的乳腺小管小叶癌,但E-cadherin、p120、β-catenin的异常表达提示E-cadherin复合体缺陷,为特殊类型的小叶癌,其生物学行为仍需进一步分析。     

乳腺浸润性导管癌神经侵犯的临床病理分析

目的探讨乳腺浸润性导管癌神经侵犯的相关临床病理影响因素。方法收集544例未经新辅助化疗的乳腺浸润性导管癌患者的临床病理资料,分析神经侵犯与乳腺癌临床病理特征的关系。结果544例乳腺浸润性导管癌中,神经侵犯阳性125例、阴性419例。单因素分析结果显示,乳腺浸润性导管癌神经侵犯与淋巴结转移数目、Ki-67增殖指数、ER及HER-2表达有关;与患者年龄、肿瘤直径、腋下淋巴结是否转移、TNM分期、脉管侵犯、分子分型、组织学分级和PR水平均无关。乳腺浸润性导管癌神经侵犯个数与患者年龄、腋下淋巴结是否转移、淋巴结转移个数及ER水平有关;与肿瘤直径、TNM分期、脉管侵犯、分子分型、组织学分级、Ki-67、PR及HER-2表达无关。多因素Logistic回归分析表明,淋巴结转移数目、ER、HER-2和Ki-67为乳腺浸润性导管癌神经侵犯的危险因素。结论乳腺浸润性导管癌患者神经侵犯与淋巴结转移数目、Ki-67增殖指数、ER及HER-2表达有关,且神经侵犯个数与患者年龄、腋下淋巴结是否转移、淋巴结转移个数及ER水平有关。     

乳腺癌中p120连环素和Bmi-1的表达及临床意义

目的 探讨p120及Bmi-1 在乳腺浸润性导管癌中的表达及其与临床病理特征的关系.方法 采用免疫组化检测135例乳腺浸润性导管癌组织中p120、Bmi-1及ER、PR、c-erbB-2表达情况,并检测了20例乳腺增生症中p120、Bmi-1表达情况.结果 p120异常表达率及Bmi-1高表达率在135例乳腺浸润性导管癌中分别为67.4% 和 48.1%,在20例乳腺增生症中分别为5%和10%,以上两组之间差异有显著性(P<0.01).p120异常表达与高组织学分级、淋巴结转移和临床较晚分期均有明显相关性(P<0.05).Bmi-1高表达与淋巴结转移、临床较晚分期均有明显相关性(P<0.05).并且,p120异常表达与Bmi-1高表达呈明显正相关(r=0.259,P<0.01).结论 p120异常表达与Bmi-1高表达在乳腺癌的发生及发展过程中可能发挥了协同或相关的作用.p120与Bmi-1可能成为预测乳腺浸润性导管癌生物学行为及指导靶向治疗的新的分子标记物.     

乳腺浸润性导管癌不同分子分型中CD90的表达及其意义

目的 探讨CD90在乳腺浸润性导管癌中的表达及其与临床病理特征、分子分型的相关性。方法 构建80例乳腺浸润性导管癌和20例乳腺良性病变的组织芯片,采用免疫组化Max Vision法检测乳腺不同病变组织中CD90、ER、PR、Ki-67和HER-2的表达水平,并进一步分析其相关性。结果 CD90在乳腺浸润性导管癌和乳腺良性病变中的阳性率分别为62.5%和20.0%,两者差异有统计学意义(P0.001);CD90表达与乳腺浸润性导管癌淋巴结转移相关(P0.05),与患者年龄、肿瘤大小、TNM分期及组织学分级无关(P0.05);在乳腺浸润性导管癌不同分子亚型中,CD90阳性率以Luminal A型最低(40.0%)、三阴型最高(82.4%),各亚型之间差异有统计学意义(P0.05);CD90与ER(r=-0.342,P0.05)、PR(r=-0.374,P0.05)表达呈负相关,与Ki-67表达之间无相关性(r=0.084,P0.05)。结论 CD90表达与乳腺癌分子分型有关,其高表达提示患者预后不良。     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

乳腺癌和癌旁乳腺组织中Notch1基因mRNA及蛋白的表达

目的 检测Notch1基因mRNA及Notch1蛋白在人乳腺癌和癌旁乳腺组织中的表达,分析其临床病理学意义.方法 应用逆转录聚合酶链反应(RT-PCR)方法榆测60例乳腺浸润性导管癌和60例癌旁乳腺组织中Notch1基因mRNA,应用免疫组织化学SP法检测60例乳腺浸润性导管癌、30例导管原位癌及60例癌旁乳腺组织Notch1蛋白的表达,分析Notch1表达水平与乳腺癌临床病理特征的相关性.结果 Notch1基因mRNA在人乳腺浸润性导管癌及癌旁乳腺组织中均有表达.Notch1蛋白在癌旁乳腺组织和导管原位癌中的阳性牢分别为55%(33/60)、70%(21/30),二者差异无统计学意义(P>0.05),在乳腺浸润性导管癌中的阳性率为90%(54/60),明显高于癌旁乳腺组织和导管原位癌的阳性率(P<0.05).乳腺浸润性导管癌Notch1蛋白的高表达与肿瘤的淋巴结转移(P=0.006)、病理学分级(P=0.001)和TNM分期(P=0.022)均呈显著正相关.结论 乳腺浸润性导管癌存在Notch1蛋白的高表达.Notch1蛋白高表达与乳腺癌的恶变演进有关.Notch1基因的表达可能影响乳腺癌的发生、发展.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

B及T细胞弱化因子基因多态性与乳腺浸润性导管癌临床关系的研究

目的 探讨B及T淋巴细胞弱化因子(BTLA)基因多态性与妇女乳腺浸润性导管癌临床关系;确定BTLA基因多态性与妇女乳腺浸润性导管癌临床关系的相关性.方法 取280例患乳腺浸润性导管癌妇女的外周血提取基因组DNA,利用聚合酶链式反应限制性片段长度多态性(PCR-RFLP)技术进行BTLA基因单核苷酸多态性检测,引用统计学软件分析其与各临床指标间的关系.结果 BTLA基因的rs1844089基因型与雌激素受体(ER)、孕激素受体(PR)和P53基因表达有关,rs2705535基因型与PR表达有关,rs9288952基因型与肿瘤大小,ER表达及PR表达有关.结论 BTLA的基因多态性中SNP的基因型与乳腺浸润性导管癌患者的肿瘤大小、ER、PR及P53基因差异具有统计学意义,而与淋巴结转移未发现有相关性.     

Tubular carcinoma of the breast and associated intra-epithelial lesions: a comparative study with invasive low-grade ductal carcinomas

Ductal intra-epithelial lesions of the breast are associated with invasive neoplasms and comprise a large spectrum of histological patterns. We have examined 23 cases of pure tubular carcinomas (TCs) of the breast and 53 cases of invasive ductal low-grade carcinomas to determine the relationship and distribution of intra-epithelial lesions, mainly of ductal in situ carcinoma type, but including also lobular intra-epithelial neoplasia (LIN) in both entities. Eleven cases of TC showed flat epithelial atypia (FEA) (47.8%), and, in 14 and 6 cases, micropapillary and cribriform low-grade ductal carcinoma in situ (DCIS) were present (60.7 and 26.1%, respectively). On the opposite, in ductal grade I invasive carcinomas, the most frequent architectural pattern was low-grade DCIS growing in arcades in 26 cases (49%). While absent in TCs, low-grade DCIS of solid type was found in five (9.4%) cases of ductal invasive carcinomas, where FEA were present in seven (13.2%) cases. LIN lesions were present in four (17.4%) cases of TC, whereas they represented 7.5%, as reported by Carstens et al. (Am J Clin Pathol 58:231–238, 1972), of cases of low-grade carcinomas. These results suggest that invasive pure TC and low-grade ductal carcinomas of the breast are different lesions, and support the fact that TC, of low histopathological grade, is a particular distinct tumoural entity.     

Chromogranin A and chromogranin B in noninvasive and invasive breast carcinoma

Recent progress in the study of chromogranins has revealed that there are many novel peptides derived from chromogranin with their multiple pathophysiologic roles. To learn the possible roles of chromogranin in breast carcinoma, we immunohistochemically investigated tissue localization of chromogranin A (CgA) and chromogranin B (CgB) in 10 normal breast tissues, 23 noninvasive ductal carcinomas (NIDCs), and 169 invasive ductal carcinomas (IDCs) and compared their expression with estrogen receptor (ER), progesterone receptor (PR), and Ki67. CgA and CgB were sporadically detected in normal cells of the ducts, acini, and luminal secretion. The expression of CgA and CgB was higher in NIDCs than in IDCs: CgA=70% of NIDC vs 22% of IDC and CgB=65% of NIDC vs 30% of IDC. There was a statistical correlation between the expression of CgA and PR (p < 0.05) and CgB and ER (p < 0.05) in IDCs without lymph node metastasis. On the other hand, there was a significant correlation between expression of CgB and PR and an inverse correlation between CgA and Ki67 in IDCs of overall cases. The data suggest that CgA and CgB may play some role in the early phase of neoplastic progression.     

Notch1 single nucleotide polymorphism rs3124591 is associated with the risk of development of invasive ductal breast carcinoma in a Chinese population

Accumulated evidence has revealed the presence of Notch receptor polymorphisms in non-tumorous diseases; however, few studies have investigated the association of Notch polymorphisms with breast cancer risk. A total of 100 invasive ductal carcinoma (IDC) and 50 ductal carcinoma in situ (DCIS) patients and 100 usual ductal hyperplasia (UDH) controls were genotyped for the following Notch receptor single nucleotide polymorphisms (SNPs) using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: Notch1, rs3124591; Notch2, rs11249433; Notch3, rs3815188, and rs1043994; and Notch4, rs367398, and rs520692. Immunohistochemistry was used to determine the effect of Notch polymorphisms on corresponding Notch protein expression in successfully genotyped patients. The frequency of rs3124591 TC genotype was significantly higher in IDC (24.7%, 20/81) and DCIS (30%, 12/40) patients than in UDH controls (8%, 8/97) (P = 0.002 and P = 0.011, respectively). However, the distribution of other SNP genotypes was not significantly different between IDC and DCIS patients and UDH controls. The frequency of TC genotype was significantly higher in poorly differentiated tumors than in well-differentiated and moderately differentiated tumors (P = 0.022). Importantly, a positive correlation between the rs3124591 TC genotype and high Notch1 protein expression was observed in DCIS patients (P = 0.043) but not in IDC patients. This is the first study to suggest an increased risk of IDC and DCIS of the breast for the Notch1 rs3124591 variant. Furthermore, given the inconsistent associations between the rs3124591 variant and Notch1 expression in IDC and DCIS, this variant may affect breast cancer risk through mechanisms in the latter stage other than alterations in Notch1 protein expression.     

Tubular carcinoma and grade 1 (well-differentiated) invasive ductal carcinoma: comparison of flat epithelial atypia and other intra-epithelial lesions

The distinction between tubular carcinomas (TC) and invasive well-differentiated (grade 1) ductal carcinoma (IDC) is important given treatment and prognostic differences. Studies have described a strong association between flat epithelial atypia (FEA) and TC. The incidence of FEA associated with grade 1 IDC is not well established. The aim of the present study was to assess morphology and intra-epithelial lesions between 14 TC and 18 grade 1 IDC matched for size. Of 14 TC, eight (57%) had associated FEA, seven (50%) had micropapillary atypical ductal hyperplasia (ADH), three (21%) had low nuclear grade ductal carcinoma in situ (DCIS), and four (29%) had lobular neoplasia. Notably, only two of 18 (11%) grade 1 IDC had associated FEA. Three of 18 (16%) grade 1 IDC had ADH, two (11%) had lobular neoplasia, and seven (39%) had DCIS. All tubular carcinomas were estrogen receptor (ER) positive and negative for Her-2/neu overexpression. All grade 1 IDC were ER positive but 5% also overexpressed Her-2/neu. Axillary lymph node metastasis was present in 11% of grade 1 IDC and absent in TC. A strong association was found between TC, FEA, and micropapillary ADH, which may reflect a biological progression. Despite matching for tumor size, grade 1 IDC have a higher incidence of lymph node metastasis and may have Her-2-neu overexpression compared to TC.     

Matriptase and survivin expression associated with tumor progression and malignant potential in breast cancer of Chinese women: tissue microarray analysis of immunostaining scores with clinicopathological parameters

Objective: The aim of this study was to examine the expression of matriptase and survivin in breast carcinoma and correlate with clinicopathological parameters. Methods: Immunohistochemical analysis of matriptase and survivin were performed in tissue microarray slides of 290 cases, including 11 normal breast tissue; 27 fibrocystic disease; 17 fibroadenoma; 6 atypical ductal hyperplasia; 39 ductal carcinoma in situ, low grade (DCIS, low grade); 39 ductal carcinoma in situ, high grade (DCIS, high grade); 27 invasive ductal carcinoma, grade I (IDC, grade I); 78 invasive ductal carcinoma, grade II (IDC, grade II); and 46 invasive ductal carcinoma, grade III (IDC, grade III). Results: The average immunostaining scores of matriptase were 44.1 in normal breast tissue, 52.7 in fibrocystic disease, 76.5 in fibroadenoma, 81.7 in atypical ductal hyperplasia, 133.7 in low-grade DCIS, and 155.8 in high-grade DCIS. Among 151 breast IDC cases, the average immunostaining scores of matriptase were 172.7 in grade I, 211.7 in grade II, and 221.2 in grade III. Additionally, the average immunostaining scores of surviving also correlate with tumor grades and stages. Conclusions: Higher expressions of matriptase and survivin correlate significantly with clinicopathological parameters in breast cancer and the malignant potential in premalignant lesions. In addition, higher survivin expression had poorer prognosis of breast IDC cases.     

Expression of maspin is up-regulated during the progression of mammary ductal carcinoma

AIMS: The tumour suppressor gene maspin is reported to inhibit the motility, invasiveness and metastasis of breast cancer cells. Maspin is expressed in normal mammary myoepithelial cells but is down-regulated during the progression of ductal carcinoma. However, we recently reported that maspin expression was frequently observed in invasive ductal carcinoma (IDC) with an aggressive phenotype, and it was a strong indicator of a poor prognosis. To our knowledge, to date, there has been no report investigating maspin expression in a large series of ductal carcinoma in situ (DCIS). METHODS AND RESULTS: To clarify whether there is down-regulation during the progression of ductal carcinoma, we immunohistochemically investigated the expression of maspin in 145 DCIS, 92 invasive ductal carcinomas with a predominant intraductal component as well as 94 usual ductal hyperplasias and 27 atypical ductal hyperplasias. The expression of maspin in carcinoma cells was observed in 9.6% (14 of 145) of DCIS and 18.5% (17 of 92) of IDC with a predominant intraductal components. It significantly correlated with larger tumour size (P = 0.013; P = 0.042), higher histological grade (P = 0.015; P = 0.0003) and the presence of comedo-necrosis (P = 0.000005; P = 0.0074) in DCIS and IDC with a predominant intraductal components, respectively. In epithelial cells, the expression of maspin was observed in only one case of usual ductal hyperplasia, and all cases of atypical ductal hyperplasia were negative. CONCLUSIONS: These results and our previous investigation in which 27.4% of IDC were positive for maspin suggest that the expression of maspin in epithelial cells could be up-regulated during the progression of ductal carcinoma, and that it could be correlated with the acquisition of an aggressive phenotype.     

Expression of cathepsin D and galectin 3 in tubular carcinomas of the breast

Tubular carcinoma (TC) is a distinctive type of grade I (G1) ductal carcinoma with particularly favourable outcome and low rate of axillary metastases. To the best of our knowledge, few data are available in the literature concerning the expression of molecules mediating intercellular and cell-matrix interactions in TC. We examined with immunohistochemical methods the expression of galectin 3 and cathepsin D in 17 TC and in 33, 31 and 28 ductal carcinomas of G1, grade II (G2) and grade III (G3), respectively. Results were compared using Chi-square test. Galectin 3 expression was higher in TC than in G1 carcinomas (p<0.05). The pattern of immunostaining was also different with a focal cytoplasmic apical reinforcement in TC. However, cathepsin D stromal and epithelial expression was similar in TC and G1 cases (p>0.05), and lower than in G2 and G3 patients at a stromal level. The higher expression of galectin 3 in TC and its focal staining (apical) pattern suggests that within the group of G1 carcinomas, galectin 3 expression varies according to histological type, and may correlate with prognosis and metastatic potential. We also suggest that cathepsin D could not be involved in neoplastic progression and metastasis in low-grade (G1) ductal breast carcinomas.     

Expression of E-cadherin and c-erbB-2/HER-2/neu oncoprotein in high-grade breast cancer

E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high-grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c-erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.     

Cyclin D1 expression in ductal carcinoma in situ, atypical ductal hyperplasia and usual ductal hyperplasia: an immunohistochemical study

The cell cycle regulatory gene, Cyclin D1, plays a critical role in the growth and progression of several types of human cancer, including breast cancer. Immunohistochemical study of Cyclin D1 expression has been extensively reported in invasive ductal carcinoma (IDC). In contrast, there have been few reports concerning Cyclin D1 expression in ductal carcinoma in situ (DCIS) and their positive rates are variable. The differences in the reported frequency may be largely due to the differences in antibodies used, immunohistochemical methods and the positive cut-off point. However, we speculated that the strictness of diagnosis of DCIS might be somewhat responsible for these differences in frequency. Therefore, we selected cases of DCIS by carefully eliminating cases of predominantly intraductal carcinoma (PIC). Moreover, to clarify whether Cyclin D1 expression is involved in multistep carcinogenesis or the progression of human breast cancer, we immunohistochemically investigated Cyclin D1 expression in 57 DCIS, 10 atypical ductal hyperplasia (ADH), 70 usual ductal hyperplasia (UDH), 44 PIC and 92 IDC. Cyclin D1 expression was detected in 41 DCIS cases (72%), 22 PIC cases (50%) and 40 IDC cases (43%). No expression of Cyclin D1 was observed in either ADH or UDH. There were no significant correlations between Cyclin D1 expression and histological grade or estrogen receptor expression in DCIS. These results suggest that Cyclin D1 expression may play an important role in the early stages of carcinogenesis, and that immunohistochemical detection of Cyclin D1 expression may be helpful in differentiating low-grade DCIS from ADH.