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].     

乳腺非浸润性癌

非浸润性癌（ｎｏｎｉｎｆｉｌｔｒａｔｉｎｇｃａｒｃｉｎｏｍａ）指乳腺实质上皮的恶性增生,未突破基底膜,无光镜下间质浸润。长期以来,普通型乳腺癌被分为导管癌和小叶癌。这是因为曾经认为导管癌发生自小叶外导管,小叶癌发生自小叶腺泡。显然,这种命名的基础是癌...     

乳腺小叶原位癌累及硬化性腺病

本次读片资料由南京大学医学院附属鼓楼医院病理科提供,通讯读片编号B7-14。患者女性,54岁(尚未绝经),体检发现左乳无痛性肿块1个月余。查体：左乳外上象限扪及一大小5 cm ×4 cm ×3 cm的质硬包块,活动度差。乳腺B超示大小5 cm ×4 cm的形状不规则、边界不清包块,遂行左乳肿块切除术并送术中快速病理检查。     

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。     

导管内原位癌几种分类方法

导管内原位癌几种分类方法詹钅容洲导管内原位癌（ｄｕｃｔａｌｃａｒｃｉｎｏｍａｉｎｓｉｔｕ，ＤＣＩＳ）的定义是乳腺导管上皮细胞的恶性增生，且局限在导管的基底膜之内，不侵犯间质。导管内原位癌是疾病的谱系，不同类型的导管内原位癌其生物学行为差异很大，其分子...     

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     

乳腺超声检查中BI-RADS分级诊断标准对乳腺原位癌的诊断价值

目的 探究应用BI-RADS分级诊断标准来诊断乳腺原位癌的超声诊断价值,以提升超声工作者对规范乳腺诊断标准认识和运用,提高彩色多普勒超声对乳腺原位癌的诊断能力。方法 选取2015年5月~2018年5月在我院通过手术及病理结果证实为乳腺原位癌的患者37例,系统回顾了根据病灶所显示出的不同声像图特征,综合分析采用BI-RADS超声分级诊断,探讨误诊主要原因。结果 37例乳腺原位癌病例中,超声诊断准确率为75.36%（28/37）,4例未定,5例误诊,其中1例误诊为导管内乳头状瘤,1例误诊为导管浸润癌,1例误诊为导管局部扩张,2例误诊为瘤样增生。结论 彩色多普勒超声诊断仪采用BI-RADS分级诊断方法,较大提高了乳腺原位癌的检出率,联合其它辅助检查可明显提高检出率,在指导临床对患者乳腺疾病的评估起到重要作用。     

24例乳腺原位癌临床治疗疗效分析

目的探讨手术治疗对乳腺原位癌临床疗效和预后的影响。方法选择24例乳腺原位癌患者,16例实施单乳切除术(66.7%),4例改良根治术(16.7%),4例行保乳手术(16.7%),对于淋巴结转移患者术后辅以化学治疗,对保乳患者术后给予全乳放疗,对临床疗效及预后情况,进行回顾性分析。结果24例乳腺原位癌患者中,20例乳腺导管原位癌,4例乳腺小叶原位癌。经过单乳切除术、改良根治术、保乳手术等综合治疗,平均随访5年,1例保乳术后5年局部复发,行乳房单切治愈,余均健在。结论采取合适的手术方式,彻底切除肿瘤病灶,辅以放疗及内分泌治疗,是提高乳腺原位癌患者预后的关键。     

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     

细胞角蛋白在鉴别乳腺乳头状瘤和乳头状导管原位癌中的作用

乳腺乳头状肿瘤是指由向腔内突起,形成纤维血管轴心的,并可演变成树枝状结构的增生的乳腺上皮组成的肿瘤,主要为导管内乳头状瘤和乳头状导管原位癌（DCIS）。尽管这两种肿瘤的组织形态学特征已有很好的描述,但在实际工作中有时区分它们还是很困难。为了寻找能够区分这两种肿瘤,作者采用免疫组化方法分析了新加坡国立医院50例乳头状肿瘤（乳头状瘤25例和乳头状DCIS25例）中CKS／CK6、CK14和3413E12的表达,     

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.     

Ductal carcinoma in situ in breast carcinogenesis

Evidence is mounting that ductal carcinoma in situ (DCIS) is a direct precursor of invasive breast cancer. Recent molecular biological and cytogenetic studies have revealed chromosomal gains and losses involved in breast carcinogenesis. This editorial discusses how the gains and losses on the different chromosomes fit into previously defined morphological routes of progression from normal cells through DCIS to invasive carcinoma, and the possible uses of these gains and losses in the classification of DCIS and the risk assessment of DCIS patients. Copyright © 1999 John Wiley & Sons, Ltd.     

Array-based comparative genomic hybridization of ductal carcinoma in situ and synchronous invasive lobular cancer

It has been increasingly recognized that ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and invasive cancer of the breast are often closely associated with one another. However, the genomic relationship between these histologically distinct entities has not been well characterized. Refinements in high-resolution comparative genomic hybridization (CGH) techniques allow for a detailed comparison of genomic alterations in synchronously occurring tumors. The following case illustrates how array CGH may be used to better understand whether synchronous neoplasms share a common origin.     

Carcinoma in situ involving sclerosing adenosis: a mimic of invasive breast carcinoma

The distinction between invasive and in situ carcinoma of the breast is important with regard to the treatment and prognosis of the patient. When carcinoma in situ involves breast tissue in which the normal architecture is altered by pre-existing sclerosing adenosis, the resulting histological picture may closely mimic an invasive carcinoma. We record the histopathological features in 13 cases where there was difficulty in identifying the presence or extent of invasive carcinoma. The most useful clue was attention to the low power appearances of distorted lobular units in the areas of malignancy and comparison with surrounding breast tissue which usually showed recognizable sclerosing adenosis. The use of immunohistochemical stains for myoepithelium (α-actin and S-100 protein) and for basement membrane (collagen type IV and laminin) proved to be of considerable value in identifying the preservation of these features around glandular structures in areas of sclerosing adenosis containing in situ carcinoma.     

A critical appraisal of six modern classifications of ductal carcinoma in situ of the breast (DCIS): correlation with grade of associated invasive carcinoma

The in-situ component of 180 cases of screen detected infiltrating duct carcinoma of the breast was classified according to six published classifications for ductal carcinoma in situ based on architecture, necrosis and cytology. All cases were assessed independently by two experienced observers to assess inter-observer variation. The differentiation of ductal carcinoma in situ as assessed by all the classification systems correlated with the grade of the associated invasive carcinoma (chi-squared between 50 and 107: P <0.0001). Disagreements were commonest in the assessment of architecture and least common in the assessment of necrosis. For cytonuclear grade most disagreements (62.2%) involved the distinction between low and intermediate as against 33.9% disagreements for intermediate vs. high. Nuclear grade alone and necrosis alone were correlated with the grade of invasive carcinoma associated with the ductal carcinoma in situ and the Nottingham prognostic index of the patient. The Van Nuys classification of ductal carcinoma in situ is commended because it has a low inter-observer disagreement, is significantly correlated with the grade of the infiltrating carcinoma, uses simple well-defined criteria (with no requirement for percentage estimations), is applicable to small numbers of ducts and, most importantly, appears to correlate with disease-free survival.     

Heterogeneous versus homogeneous genetic nature of multiple foci of in situ carcinoma of the breast

The vast majority of in situ breast cancers represent focal lesions all derived from a single clone and requiring local treatment alone. We focused our attention on rare cases of multicentric in situ carcinomas affecting different quadrants, which required mastectomy. Defining the origin from single- or multiple-cell clones of separate independent neoplastic foci in the breast may be of pathogenetic interest and of importance in deciding the type of therapy to be administered. We employed a molecular assay based on loss of heterozygosity (LOH) and human androgen receptor assay (HUMARA) analysis of microdissected samples from 19 mastectomies. Two or more tissue samples were obtained from 7 patients with multicentric lobular in situ carcinoma (LCIS), either classical or large-cell variety; and 12 patients with multicentric ductal in situ carcinomas (DCIS), either low-grade (7 cases) or high-grade (5 cases) variety. Separate foci of high-grade (comedonic) DCIS were found to be monoclonal in nature. On the contrary, definite evidence favoring the origin from different cell clones of separate carcinomatous foci within the same breast was obtained in 2 cases of low-grade DCIS and in 6 cases of LCIS. A genetic imbalance might be the factor favoring the development of multifocal heterogeneous foci of in situ breast cancer. Such a small subgroup of in situ cancers affecting diffusely the entire breast and originating from independent foci presents both clinical and pathogenetic interest.     

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.     

Lobular cancerization: incidence and differential diagnosis with lobular carcinoma in situ of breast

A series of 120 breast biopsies and mastectomy specimens originally diagnosed as carcinoma was reviewed in order to emphasize the differences between lobular carcinoma in situ and cancerization of lobules. Criteria for differential diagnosis between the two types of lobular lesion are proposed. In the reviewed material 15 (12.5%) cases of lobular carcinoma in situ and 64 (53.3%) of lobular cancerization were found. The carcinoma in situ usually co-existed with other types of breast carcinoma, such as intraductal carcinoma, cancerization and invasive carcinoma of different types.     

用荧光原位杂交技术检测乳腺癌细胞系第6号染色体长臂缺失

目的 研究１０例乳腺癌细胞系的６号染色体第臂缺失。方法 运用荧光原位杂交（ｆｌｕｏｒｅｓｃｅｎｃｅ ｉｎ ｓｉｔｕ ｈｙｂｒｉｄｉｚａｔｉｏｎ,ＦＩＳＨ）技术,并采用３７个分布于６ｑ１２－６ｑ２７的ＹＡＣ探针和６号染色体着丝粒特异性探针,检测了１０例乳腺癌细胞系的６号染色体长臂。结果 在５例细胞系中发现６ｑ１２－６ｑ２７的大段缺失,１例发现有６ｑ２５－ｑ２７的小段缺失。在含有多个细胞亚群的两侧细胞