乳腺导管原位癌病理形态及c—erbB—2,p53和PCN…

目的：对乳腺导管原位癌进行病理形态分析，并行ｃ－ｅｒｂＢ－２、ｐ５３癌基因蛋白、增殖细胞抗原（ＰＣＮＡ）表达以及相关性的研究，以期为临床判断潜在恶性程度及预后提供参考指标。方法：运用病理形态分析以及枸橼酸－微波－ＡＢＣ免疫组化法对２５例 马林固定、石蜡包蛙乳腺导管原位癌组织进行回顾性研究。结果：（１）２５例乳腺原位导管癌ｃ－ｅｒｂＢ－２、ｐ５３、ＰＣＮＡ表达的阳性率分别为３６．０％，４０．０和４０     

乳腺乳头状瘤病和导管原位癌cyclinD1、p16和Ki-67表达

目的　探讨细胞周期调控因子cyclinD1、p16和Ki 6 7与乳腺乳头状瘤病及导管内癌的相关性及其临床病理意义。方法　通过免疫组化S P法检测轻度乳头状瘤病、重度乳头状瘤病和导管内癌各 4 0例中cyclinD1、p16和Ki 6 7的蛋白表达情况 ,并用 2 0例正常乳腺组织作对照。结果　cyclinD1在轻度、重度乳头状瘤病和导管内癌组中阳性率分别为 2 7 5 %、5 0 0 %、6 0 0 % ,3组间差异有显著性 (χ2 =8 92 9,P <0 0 5 )。p16蛋白表达分别为 80 0 %、5 2 5 %、4 0 0 % ,3组间差异均有显著性 (χ2 =8 6 87,P <0 0 1)。轻度与重度乳头状瘤病组比较均有差异 ,但重度乳头状瘤病与导管内癌组间差异无显著性。Ki 6 7阳性率在 3组间差异有显著性 ,组间两两比较也分别有统计学差异。在各组中 ,Ki 6 7与cyclinD1呈正相关 ,与 p16呈负相关 ,cyclinD1与 p16呈负相关。结论　cyclinD1、p16和Ki 6 7表达异常在乳腺癌发生、发展演进过程中是一种早期事件。重度乳头状瘤病是重要的癌前病变。调节cyclinD1和 p16的平衡可能是癌前病变基因治疗的一条途径     

乳腺导管原位癌研究新进展

随着乳腺摄片筛查技术的广泛应用,发现近年乳腺导管原位癌(ductal carcinoma in situ,DCIS)的发病率明显增高.上世纪70年代初期,乳腺癌病例中的DCIS低于1%,而目前则占20%～30%[1].DCIS是一组异质性病变,特征是局限于乳腺导管的恶性上皮细胞克隆性增生,光镜下尚未突破基膜.从理论上讲,DCIS缺乏转移潜能且仅外科手术切除即可治愈.然而,DCIS常常以原位癌或浸润性癌形式复发,因此DCIS是潜在的致死性疾病[2].     

乳腺导管原位癌外科手术治疗的研究进展

乳腺导管原位癌是一种多发恶性肿瘤,其本质为癌细胞累及上皮全层,且仅局限在导管内尚未突破基底膜的肿瘤。近年来,随着医学技术的快速发展,乳腺导管原位癌检出率明显提升,且治疗措施也相应改进。外科手术是临床上常用的治疗乳腺导管原位癌的方法,且涉及手术类型较多,效果不一。文章对临床上外科手术治疗乳腺导管原位癌的研究进行综述,以期为临床实践和研究提供必要的参考依据。     

乳腺浸润性导管癌伴导管原位癌

<正>1临床资料本例读片资料由山西省肿瘤医院病理科提供,通讯读片编号BB19-8。患者女性,35岁,于2017年6月入院,发现右侧乳腺肿物5个月,无明显触痛,局部皮肤红肿。外院影像超声:低回声结节,大小2 cm×1. 7 cm,形态欠规则,周界不清。当地医院局部术后病理诊断:乳腺癌;会诊:浸润性癌,不除外化生性癌。患者无既往史,入院行根治术:右侧乳腺改良根治术,     

c─erbB─2、ras p21及p53在大肠癌表达的免疫组化研究

对４８例大肠癌连续切片进行ｃ─ｅｒｂＢ─２、ｒａｓｐ２１及ｐ５３３种癌相关基因产物的免疫组化ＡＢＣ法及ＡＰＡＡＰ－ＩＧＳＳ双重标记研究，结果表明：（１）癌相关基因ｃ─ｅｒｂＢ─２、ｒａｓｐ２１和ｐ５３阳性表达率在癌组织分别为５０．２％（２５／４８）、４３．８％（２１／４８）和５４．２％（２６／４８）；癌旁粘膜分别为２５％（１２／４８）、１８．８（９／４８）和２０．８％（１０／４８）；而在＂正常＂结肠粘膜则分别为１２．５％（６／４８）、６．３％（３／４８）和０．（２）有２种以上癌相关基因产物同时表达者在癌组织中有２６例（５４．２％）．在癌旁粘膜有５例（１０．５％），而在正常粘膜则未见有２种癌相关基因同时表达，（３）癌组织中ｃ─ｅｒｂＢ─２＋ｐ２１、ｃ─ｅｒｂＢ─２＋ｐ５３、ｐ２１＋ｐ５３及ｃ─ｅｒｂＢ─２＋ｐ２１＋ｐ５３同时表达者分别为２．１％、１２．５％、１６．７％及２２．９％，（４）ＡＰＡＡＰ－ＩＧＳＳ双重免疫标记结果表明，单一癌细胞可同时表达２种癌基因产物。上述结果提示：ｃ─ｅｒｂＢ─２、ｒａｓｐ２１及ｐ５３可能与大肠病的发生有关，三者在大肠病的发生中可能起协同作用。     

乳腺导管非典型增生p53,增殖细胞核抗原和肌动蛋白的表达

我们应用免疫组化技术 ,对乳腺导管上皮增生性病变的ｐ5 3、增殖细胞核抗原 (ＰＣＮＡ)和肌动蛋白的表达进行联合检测 ,探讨这些免疫标记物对于估测乳腺导管上皮非典型性增生 (ＡＩＤＨ)恶变潜能和交界性病变良恶性质的意义。一、材料和方法1 材料 :标本系本教研室 1980～ 1997年间以及天津市塘沽医院和第二中心医院同期的存档蜡块。参考ＷＨＯ的组织学分类标准 ,选择 :(1)乳腺导管上皮中、重度单纯性增生(增生组 ) 6 5例 ,其中中度 2 3例 ,重度 42例 ;(2 )非典型增生(非典组 ) 30例 ;(3)浸润性导管癌 (导管癌组 ) 4 0例 ;(4)正常乳腺活检标…     

乳腺癌发生过程中p53、BRCA1、BRCA2、PTEN、Rb蛋白异常表达

目的探讨p53、BRCA1、BRCA2、PTEN、Rb基因蛋白异常表达在乳腺癌发生中的作用。方法选取同时存在浸润癌、导管内癌、不典型增生和单纯性增生的乳腺癌档案蜡块,应用免疫组化S-P法检测p53、BRCA1、BRCA2、PTEN、Rb基因蛋白在各例的异常表达。结果(1)在24．3％(17／70)的乳腺癌及其癌旁不典型增生中检测到突变型p53蛋白表达,分别在2．9％(2／69)、6．3％(4／63)、5．1％(3／59)、5．4％(3／56)的乳腺癌及其癌旁不典型增生中分别检测到BRCA1、BRCA2、PTEN、Rb表达缺失。(2)在44．6％的病例同时检测到2种基因蛋白异常表达,在5．4％的病例同时检测到3种基因蛋白异常表达,在3．6％的病例同时检测到4种基因蛋白异常表达。结论(1)p53、BRCA1、BRCA2、PTEN、Rb蛋白异常表达可出现于乳腺癌发生的早期阶段,可能在乳腺癌发生过程中起作用。(2)多种抑癌基因的失活共同参与了乳腺癌的发生。     

乳腺癌中p27和c-erbB-2的表达及意义

目的　探讨乳腺癌中 p2 7和c erbB 2表达情况和意义。 方法　用免疫组化S P法检测 4 0例乳腺癌中 p2 7和c erbB 2的表达。结果　正常乳腺组织c erbB 2表达阴性 ,癌组织中阳性率为 37 5 % (15 / 4 0 ) ,两者差异有显著性 (P <0 0 0 1)。 4 0例乳腺癌组织中 p2 7高表达率为 32 5 % (13/ 4 0 ) ,正常乳腺组织高表达为 80 % ,两者差异有显著性 (P <0 0 0 1)。p2 7高表达与癌组织分化、淋巴结转移和复发有关 (P <0 0 5 )。结论　基因p2 7和c erbB 2表达异常是乳腺癌产生的机制之一 ,与乳腺癌的发生及发展有关。p2 7可能是乳腺癌的一个重要预后指标     

HER-2、p16、p53蛋白在乳腺浸润性导管癌中的表达及意义

目的探讨HER-2、p16、p53蛋白在乳腺浸润性导管癌中的表达情况及其临床意义。方法收集2008年7月～2010年12月商丘市中心医院行手术治疗,术后证实为乳腺浸润性导管癌患者149例,检测HER-2、p16、p53蛋白在乳腺浸润性导管癌中以及正常组织中的表达情况。结果乳腺浸润性导管癌HER-2过表达,阳性率为23.5%;p16、p53阳性率分别为31.5%和51.0%;HER-2过表达与腋窝淋巴结转移、组织学分级存在明显相关性(χ2=5.687、5.924,P均<0.05);p16阳性表达在不同年龄之间存在统计学差异(χ2=4.213,P<0.05),p53阳性表达在不同组织学分级之间存在统计学差异(χ2=6.378,P<0.05);HER-2、p16表达与术后无瘤生存存在明显的相关性;p16与p53存在明显相关性(r=0.282,P<0.05)。结论 HER-2、p16、p53与乳腺浸润性导管癌的发生、发展密切相关,可作为临床指导治疗和评价患者预后的重要指标。     

Combined evaluation of CK5/6, ER, p63, and MUC3 for distinguishing breast intraductal papilloma from ductal carcinoma in situ

The differentiation of intraductal papilloma (IDP) in the breast from ductal carcinoma in situ (DCIS) is sometimes difficult. Fifty papillary lesions (25 DCIS and 25 IDP) were immunohistochemically examined using a panel of antibodies, including CK5/6, ER, p63, Ki-67, chromogranin A, synaptophysin, neuron specific enolase, CD56, MUC1, MUC3, CD44, p21, p27, and p53. The immunohistochemical staining pattern of each antibody was evaluated using the Allred scoring system. Then, the area under curve (AUC) for each antibody was computed by receiver operating characteristic (ROC) analysis. DCIS typically showed high scores for ER and MUC3 reactivity compared with IDP, and the AUC for ER and MUC3 were 0.941 and 0.908, respectively. In contrast, IDP showed high scores for CK5/6 and p63 reactivity compared with DCIS, and the AUC for CK5/6 and p63 were 1.00 and 0.954, respectively. We devised a 'Differential Index' (DI) using the following formula: [S(ER) + S(MUC3)]/[S(CK5/6) + S(p63) + 1]. The distributions of the DI for IDP and DCIS did not overlap when the cutoff value was placed arbitrarily at DI = 1.0. From these results, it is concluded that a panel of four CK5/6, ER, p63, and MUC3 antibodies provide valuable information for differentiating IDP from DCIS.     

乳腺导管内癌分子分型应用研究

目的 采用免疫组织化学检测方法 对乳腺导管内癌进行分子分型.方法 收集50例乳腺导管内癌存档蜡块,用单克隆抗体CK5/6、CK8、CK18、34βE12、p63、S-100、SMA、CD10、CD117、EGFR、ER、PR和HER2进行免疫组织化学EnVision法染色,按照免疫表型分为5种类型:腺腔A型(ER+/PR+/HER2-)、腺腔B型(ER+/PR+/HER2+)、正常乳腺样型(ER-/PR-/HER2-且不表达基底/肌上皮标记及EGFR)、HER2过表达型(ER-/PR-/HER2+)和基底细胞样型(ER-/PR-/HER2-,且至少表达一种基底型角蛋白和(或)肌上皮标记物或EGFR).结果 腺腔A型16例(32%),腺腔B型19例(38%),HER2过表达型13例(26%),基底细胞样型2例(4%),无正常乳腺型.2例基底细胞样型,均表达CK5/6、CD117,例1同时表达SMA,例2表达CK8、CK18、34βE12、S-100,均为高级别导管内癌.结论 乳腺导管内癌可按免疫表型进行分子分型,部分导管内癌具有与基底细胞样癌相同的免疫表型,可能是基底细胞样癌的前驱病变,其诊断依赖于免疫组化检测.     

Cytological criteria for the diagnosis of intraductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma of the breast

The advent of mammography screening presents a diagnostic challenge to the cytopathologist as an increasing proportion of breast lesions requiring investigation will be nonpalpable and up to 40% will be accounted for by atypical intraductal hyperplasia and ductal carcinoma in situ, as opposed to previously, when these lesions represented less than 10% of palpable tumors. We studied 133 fine-needle aspirates from breast tumors and found that nuclear morphology, myoepithelial cells, signs of invasion, and degree of cellular dissociation are among the most potent factors discriminating between benign epithelial proliferations, atypical intraductal hyperplasia, ductal carcinoma in situ, and invasive carcinoma.     

CD24 expression in ductal carcinoma in situ and invasive ductal carcinoma of breast: an immunohistochemistry-based pilot study

CD24 is a small, heavily glycosylated cell surface protein, that is expressed in a large variety of solid tumors. It is considered to play an important role in tumor progression and metastasis. We aimed to evaluate CD24 expression in invasive ductal carcinomas (IDCa), ductal carcinoma in situ (DCIS) and non-tumorous breast tissues, and to investigate the relationship between histopathological parameters, estrogen and progesterone receptors, and c-erbB2 expressions. The study included 34 IDCa, 25 DCIS, and 13 non-tumorous breast tissues. All cases were reevaluated histopathologically, and immunohistochemistry was performed with monoclonal CD24 antibody. The results clearly demonstrated that CD24 expression, including membranous and cytoplasmic staining, was significantly higher in DCIS and IDCa than in the non-tumorous breast (p=0.001, p=0.000, and p=0.035, p=0.000, respectively). Cytoplasmic staining was detected predominantly in neoplastic tissues and was significantly increased in high grade DCIS (p=0.013). In invasive carcinomas, although the level of membranous staining was significantly positively correlated with tumor grade (p=0.040), there was no such an association with the cytoplasmic level. However, it showed a trend towards pT (p=0.089). In conclusion, our results suggest that higher CD24 expression may be associated with malignant transformation and progression in breast cancer biology. Furthermore, higher membranous expression and, in particular, cytoplasmic staining seem to predict malignant transformation, and different patterns of CD24 expression may be associated with different pathological features in breast tumors.     

HER2 status in pure ductal carcinoma in situ and in the intraductal and invasive components of invasive ductal carcinoma determined by fluorescence in situ hybridization and immunohistochemistry

AIM: To determine the HER2 status of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) of the breast. The increased prevalence of HER2 amplification and overexpression in DCIS is considered to be maintained in the intraductal component of IDC; however, HER2 amplification and overexpression are detected much less in IDC. METHODS AND RESULTS: Fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) were performed to detect HER2 in 270 IDCs with an intraductal component and in 50 pure DCIS samples; IHC was also performed in 116 metastatic nodes. HER2 was found to be amplified in 77 cases (28.5%) and overexpressed in 79 (29.3%) of the 270 IDCs. HER2 amplification was similar between intraductal and invasive components of the same tumour. The concordance for HER2 status between invasive and intraductal components of individual tumours was 98.5% and 99.3% by FISH and IHC, respectively. HER2 was amplified in 25 (50%) of the 50 pure DCIS samples. HER2 overexpression in metastatic nodes resembled the HER2 status in the primary tumour for 108 (93.1%) of 116 cases (kappa =0.831). CONCLUSION: Our study indicates that the intraductal component of IDC may differ biologically when compared with pure DCIS. HER2 appears to lack a critical role in the progression from DCIS to IDC and HER2 status is maintained in metastatic lesions.     

Recognizing breast ductal carcinoma in situ on fine‐needle aspiration: A diagnostic dilemma

In this study, we evaluated cytomorphologic features of different subgroups of ductal carcinoma in situ (DCIS); we compared seven cytologic features between DCIS and invasive ductal carcinoma (IDC) aspirates to determine whether diagnosis of stromal invasion can be made based on fine‐needle aspiration (FNA) findings. There were 142 cases of DCIS and 1,978 cases of IDC enrolled in our study. FNA analysis revealed 80.3% sensitivity for DCIS and 94.7% sensitivity for IDC. High and intermediate grade DCIS exhibited marked nuclear abnormality (92.1% vs. 35.7%, 30.0%; P1 < 0.001, P2 < 0.001) and necrosis (69.7% vs. 0%, 10.0%; P1 < 0.001, P2 = 0.001) in a higher percentage of cases compared to low grade DCIS and intraductal/intracystic papillary carcinoma. The rates of background macrophages (71.3% for DCIS and 21.9% for IDC, P < 0.001) and extensive necrosis (54.0% for DCIS and 16.7% for IDC, P < 0.001) were significantly higher in DCIS compared to IDC. Lymphocytes were observed in conjunction with tumor cells more frequently in IDC (81.3%) compared to DCIS (36.8%, P < 0.001). Stromal fragments associated with tumor cells were only observed in invasive lesions (11.9% micro‐invasive DCIS and 52.1% IDC). Tubular structures were found exclusively in IDC (11.5%). Cytologic criteria for diagnosis of high and low grade DCIS are different. The suspicion of DCIS is raised when background macrophages and extensive necrosis are observed. Stromal invasion is suggested by FNA if lymphocytes are entwined around tumor cells or if stromal fragments associated with tumor cells or tubular structures are observed. Diagn. Cytopathol. 2013;41:710–715. © 2013 Wiley Periodicals, Inc.     

Microinvasive ductal carcinoma (T1mic) of the breast. The clinicopathological profile and immunohistochemical features of 28 cases

Microinvasive ductal carcinoma of the breast, namely ductal carcinoma in situ with microinvasion (T1mic) as defined by the American Joint Committee on Cancer (AJCC) Staging Manual, is a rare disease, although it is increasing because of widespread use of mammography. The aim of the present study was to describe the clinicopathological and immunohistochemical features of this entity. Twenty-eight patients who were diagnosed as T1mic from January 1997 to August 2002 were studied by using 3-5 mm-thick serial sections with hematoxylin-eosin staining. Immunohistochemical staining for the estrogen receptor (ER), progesterone receptor (PR), p53, Ki-67, and HER-2 were performed. All 28 patients were female, with a mean age of 48.8 years. Twenty-six patients (93%) revealed mammographic abnormalities on routine examination. All foci of the invasions were measured using an ocular micrometer. Invasive foci consisted of isolated cells or cell clusters, or appeared as a tongue-like projection of tumor through the basement membrane of the duct of ductal carcinoma in situ (DCIS). The mean number of invasive foci was 3, and the mean size was 0.6 mm. We found that high nuclear grade and predominant comedo subtype of DCIS components were 57.1% and 46.4%, respectively. Twenty-four cases (86%) demonstrated necrosis of DCIS components. Microinvasion was often associated with periductal stromal reaction (71.5%) and/or a lymphocytic infiltration (78.6%). All patients, excluding two, received axillary resection (the mean number of lymph nodes examined per case was 12), and none had lymph node metastasis. The positive expression of ER and PR strongly related to low grade nuclei and non-comedo subtype; however, the positive expression of HER-2 and P53 related to high grade nuclei and comedo subtype (P<0.01). Ki-67 expression was significantly higher in the high grade nuclei group than in the low grade group (P<0.01). Our study suggested that high nuclear grade and comedo DCIS were more aggressive and more common with microinvasion, and that microinvasion is more likely to be multifocal.     

Loss of bcl-2 expression in ductal carcinoma in situ of the breast relates to poor histological differentiation and to expression of p53 and c-erbB-2 proteins

Aim : This study (1) investigates the incidence of bcl-2 protein expression in a series of 108 cases of ductal carcinoma in situ (DCIS), including 25 with early invasive carcinoma, and (2) evaluates the relationship of bcl-2 expression to the histological grade of DCIS and to the expression of oestrogen receptor (ER), c-erbB-2 and p53 proteins.  

Methods and results

The expression of bcl-2, oestrogen receptor (ER), c-erbB-2 and p53 proteins was determined immunohistochemically. Cases were regarded as positive for individual antibodies when at least 10% of the DCIS cells showed positive staining. DCIS was graded histologically as well ( n  = 9), intermediately ( n  = 24), or poorly differentiated ( n  = 75). bcl-2 expression was documented in 57 cases (53%) and was strongly associated with the histological grade of DCIS ( P  < 0.0001). All cases of well-differentiated DCIS were bcl-2 positive and loss of bcl-2 expression was almost exclusively confined to poorly differentiated DCIS lesions. bcl-2 expression was also closely associated with positive ER status ( P  < 0.0001). Forty-seven of 57 (82%) bcl-2 positive cases were ER positive while 49/51 (96%) bcl-2 negative cases were ER negative. There was a significant inverse correlation between bcl-2 expression and both p53 protein expression ( P  = 0.0004) and c-erbB-2 expression ( P  < 0.0001). Nineteen of 24 (79%) p53 positive cases and 38/45 (84%) c-erbB-2 positive cases showed loss of bcl-2.  

Conclusions

Loss of bcl-2 expression occurs in poorly differentiated DCIS and is related to negative ER status and to positive p53 and c-erbB-2 status. This pattern of bcl-2 expression and its association with other biological markers in DCIS is similar to that reported in invasive breast carcinoma.     

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.     

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.