乳腺癌切除标本内导管内增生性病变的免疫表型观察

目的探讨乳腺癌切除标本内导管内增生性病变的形态和免疫表型特点及其与浸润癌的关系。方法筛选出浸润性导管癌切除标本内有较多癌旁组织的病例36例和同期乳腺良性病变28例(对照组),选用CK5、CK34βE12、S100蛋白、SMA、CK8、Ecad、cerbB2等7种抗体做免疫组化染色。结果乳癌组36例中28例伴导管内增生性病变,单纯或复合出现的病变包括:普通性导管增生7例,柱状细胞病变12例,不典型导管增生4例,导管原位癌24例,伴两种以上病变者10例,4种病变同时存在者2例。对照组中计普通性导管增生23例,柱状细胞病变9例。免疫组化提示CK5在旺炽型UDH中腺系上皮细胞有大量表达,不典型导管增生、导管原位癌及浸润性导管癌中其表达明显降低直至完全失表达;CK34βE12表达类似于CK5,但较CK5为强,二者并不完全重合;S100蛋白表达于肌上皮细胞和增生的腺系上皮细胞,其在UDH的腺系上皮中的表达近似于CK34βE12,却不表达SMA;在24例高级DCIS中,11例肌上皮对S100蛋白的反应性先消失,但对SMA仍呈强反应;Ecad在导管原位癌、浸润性导管癌中出现再表达和(或)阳性等级升高;cerbB2在高级DCIS和IDC中呈清晰的膜表达。结论77.87%浸润性导管癌伴有不同的导管内增生性病变,这些病变不仅形态学表现不同,且免疫表型有异,可据此协助诊断与鉴别诊断。仅据对活检诊断的导管内增生性病变患者长期随访而得出的后来发生浸润性乳腺癌危险度的结论,与当初诊断的病变并无直接相关,而更可能与当初残留或后来发生的导管内增生性病变有关。     

细胞角蛋白34βE12在鉴别乳腺良、恶性病变中的意义

目的 探讨高分子量细胞角蛋白34βE12作为良性病变的标记物对鉴别乳腺病变的意义。方法收集90例有随访活检和组织病理学诊断对照的乳腺细针吸取细胞学(FNAC)资料：良性病变50例,包括非增生性病变30例和增生性病变20例、导管内癌10例和浸润癌30例,对其FNAC涂片和相应的石蜡切片作34βE12的抗生物素蛋白-生物素-过氧化酶复合(ABC)法免疫组织化学分析。利用SPSS10．0软件进行统计学分析。结果 (1)34βE12在良性非增生和增生性病变组中的表达差异无显著性。(2)34βE12在良性病变和癌组中的表达差异具显著性,34βE12在癌组中,FNAC涂片和相应的石蜡切片分别为66．7％和63．3％的病例表现为完全阴性或散在1 的肿瘤细胞胞质阳性;在良性病变组中,FNAC涂片和相应的石蜡切片分别为100％和78％的病例表现为2 至3 的细胞阳性,且在石蜡切片中34βE12表现为完整的细胞膜和细胞质的强阳性,与癌中阳性标本之细胞质颗粒状阳性为主的表达特点不同。(3)34βE12在细胞分化较好的筛孔型、乳头型和实性型导管内癌中为完全阴性和散在细胞胞质阳性,而在细胞分化较差的粉刺型导管内癌中为阴性至3 的细胞阳性。结论 34βE12可作为乳腺病变鉴别诊断中良性病变的标记物,上皮细胞出现34βE12表达缺失时高度提示为癌;大量上皮细胞表达34βE12,且为细胞膜强阳性时,则应多考虑为良性病变。     

基底型细胞角蛋白在乳腺导管内增生性病变诊断中的应用

目的比较不同类型基底型细胞角蛋白(CK5、CK34βE12和CK14)在乳腺导管内增生性病变中的辅助诊断价值,并结合肌上皮标记、超微电镜对普通型导管增生的细胞成分进行初步分析。方法参照2003年WHO乳腺疾病分类的诊断标准筛选出28例导管普通型增生(UDH)、10例不典型增生(ADH)和25例导管原位癌(DCIS)。所有病例均进行CK5/6、CK34βE12、CK14、CK8、浕SMA、calponin和p63的免疫组化染色。4例UDH和1例DCIS通过电镜观察其增生细胞的超微结构。结果CK5/6在UDH、ADH和DCIS增生细胞中的阳性表达率分别为92.9%、10.0%和0。CK34βE12和CK14的阳性表达率分别为96.4%和82.1%(UDH)、20.0%和30.0%(ADH)、24.0%和28.0%(DCIS)。所有UDH的增生细胞均不表达浕SMA、calponin和p63。电镜观察显示UDH和DCIS的增生细胞中未发现符合肌上皮超微特征的细胞存在。结论基底型CK有助于UDH和ADH/DCIS的鉴别诊断,其中CK5/6较CK34βE12和CK14特异性更高。免疫组化染色和电镜观察结果支持UDH的增生细胞含有多种成分,包括定向干细胞、腺中间细胞和腺终端细胞等,但未发现具有肌上皮特点的细胞参与其中。     

乳腺导管内乳头状肿瘤的形态学和免疫表型特征

目的观察乳腺导管内乳头状肿瘤（intraductal papillary neoplasms,IDPN）的形态学和免疫表型特征,并探讨其诊断。方法根据WHO分类（2003）和Tavassoli等（1999、2003）有关标准,筛选出乳腺导管内乳头状肿瘤41例,对上述病例进行HE形态观察和免疫组化检测,选用的一抗有CK5、CK34βE12、CK8、CD34、SMA、p63、CD10。结果（1）导管内乳头状瘤19例,镜检为扩张的导管或小管内含纤维-脉管轴心的乳头状病变,由腺（系）上皮和肌上皮覆盖轴心形成双层构型。其中16例伴腺（系）上皮普通性增生,2例〈10％的乳头覆盖上皮呈不典型增生（AH）改变。腺（系）上皮CK5 17例（89．5％）中～强阳性;CK34βE1216例（84．2％）中～强阳性。肌上皮SMA、p63、CD10均阳性。（2）非典犁导管内乳头状瘤4例,3例伴发于囊内乳头状癌,1例作为主要诊断。表现为≥10％而〈90％的乳头覆盖上皮呈AH改变。其AH区域CK5均阴性,3例CK34βE12阴性～弱阳性。（3）导管内乳头状癌21例,其中①2例仅表现为≥90％的乳头区肌上皮层完全缺乏;②1例仪表现为〉90％的乳头覆盖上皮呈低级导管原位癌（DCIS）样改变;③8例兼具上两种特征;④10例乳头覆盖上皮呈中～高级别DCIS样改变。符合②及③者CK5均阴性,CK34βE12 6例（66．7％）阴性～弱阳性;符合④者CK5、CK34βE12 8例（80％）均阴性～弱阳性。结论IDPN是一组良恶性不同的病变,各自的HE形态和免疫表型均有差异,应采用HE形态和免疫组化相结合的综合标准进行诊断。     

乳腺导管不同类型增生性病变中p63和 CK5/6的表达及意义

目的：明确不同类型的乳腺导管增生性病变中p63和Cytokeratin 5/6(CK5/6)的表达和意义。方法：对150例乳腺导管增生性病变中的368个病灶分别进行p63和CK5/6染色。结果：CK5/6在正常乳腺组织中的肌上皮和导管上皮均阳性表达，35例普通型增生中，33例CK5/6呈马赛克式阳性表达，仅2例弥漫阳性；在非典型性增生、原位癌和浸润癌中，CK5/6主要呈阴性表达，仅6例阳性，其中有2例雌激素受体（estrogen receptor, ER）、孕激素受体（progesterone receptor, PR）和CerbB 2阴性，符合基底细胞样癌的特点。p63在良性病变和非浸润性肿瘤性增生病变中的肌上皮细胞阳性表达，3例原位癌不表达p63和CK5/6。浸润癌中有3例（3/43）p63散在肿瘤细胞阳性，其余均阴性。结论：不同类型乳腺增生性病变中p63及CK5/6的染色模式存在一定规律，有助于这些病变的诊断和鉴别诊断。     

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…     

乳腺增生性病变中p63蛋白的表达及意义

目的 探讨p63蛋白在乳腺疾病诊断以及鉴别诊断中的应用价值。方法 对38例不同类型的乳腺病变分别进行p63、SMA、S-100蛋白、CK(34βE12)免疫标记。结果 p63蛋白在乳腺良性增生性病变腺体肌上皮细胞核有阳性表达,围绕在腺体周围,原位癌癌巢周围肌上皮细胞数目减少,呈间断性分布,浸润性癌癌巢周围肌上皮细胞大部分消失或无肌上皮细胞分布,且阳性表达强度与肿瘤分化程度相关。其他基底细胞标记物也可以比较特异地显示乳腺腺体周围肌上皮,但存在一定的非特异性着色。结论 从乳腺正常组织、良性病变至原位癌、早期浸润和浸润性癌,腺体周围的肌上皮细胞呈逐渐消失的趋势,p63蛋白标记可以比较特异地反映这个过程,而且受其他影响因素小。     

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。     

乳腺导管上皮内瘤变

乳腺导管上皮内瘤变(ductal intraepithelial neoplasm)是一个新概念。该概念包含乳腺导管上皮增生(IDH)、导管上皮不典型性增生(AIDH)以及导管原位癌或导管内癌一系列导管上皮增生性病变。由IDH到导管原位癌构成了一个由良性到恶性病变的渐变谱系，进一步则演变为浸润性导管癌(IDC)。导管上皮内瘤变诊断难点主要集中于AIDH同     

乳腺放射状硬化性病变的病理形态学观察

目的 探讨乳腺放射状硬化性病变的组织病理特点和鉴别诊断.方法 收集44例乳腺放射状硬化性病变,进行组织形态学和免疫组织化学SP法或EnVision二步法染色观察.结果 44例均发生在女性,年龄17～54岁(平均40.3岁).31例会诊者中13例误诊为癌.镜下病变呈放射状,中央为纤维瘢痕区,其内常有受压变形的腺管,周围有放射状分布的扩张腺管及不同程度增生的导管和小叶,可伴大汗腺、柱状细胞化生增生,其中14例见坏死,8例伴不典型导管增生.免疫组织化学染色显示纤维瘢痕组织内假浸润的变形腺管周围有肌上皮,旺炽性增生的上皮呈CK5/6阳性.结论 乳腺放射状硬化性病变有特殊的形态特点,易误诊为癌,需与导管内癌、小叶性肿瘤、小管癌、浸润性导管癌鉴别.     

Value of cytokeratin 5/6 immunostaining using D5/16 B4 antibody in the spectrum of proliferative intraepithelial lesions of the breast. A comparative study with 34βE12 antibody

Previous studies have shown that basal-type cytokeratins (CKs) can distinguish usual ductal hyperplasia (UDH) from the spectrum of atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). Indeed, expression of these CKs is weak or absent in ADH, DCIS and LCIS. However, the diagnostic usefulness of D5/16B4 antibody (anti-CK5/6) has never been compared with that of 34betaE12 antibody (anti-CK1/5/10/14). We performed immunostaining of CK 5/6 and CK1/5/10/14 on 100 breast lesions, including UDH ( n=31), ADH ( n=5), DCIS ( n=54) and LCIS ( n=10). Abundant immunostaining was observed in all UDH using both antibodies. Four of five of the ADH cases showed less than 5% of CK5/6 stained cells, the remaining case showed 30% of labeled cells. With 34betaE12 antibody, three of five of the ADH cases showed less than 5% labeled cells, while two cases showed more than 30% of stained cells. None of the 54 DCIS or the 10 LCIS was labeled by D5/16B4, while a lack of 34betaE12 immunostaining was observed in only 15 of 54 DCIS and 2 of 10 LCIS. We confirmed that D5/16B4 antibody directed against CK5/6 is useful in distinguishing UDH from the spectrum of ADH/DCIS/LCIS. We also demonstrated that D5/16B4 is far a more specific marker than 34betaE12 antibody.     

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.     

Immunohistochemical analysis of 14-3-3 sigma and related proteins in hyperplastic and neoplastic breast lesions, with particular reference to early carcinogenesis

In order to confirm the role of 14-3-3 sigma (sigma) as a tumor suppressor in breast carcinogenesis, we have studied the expression of 14-3-3sigma immunohistochemically in usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) breast lesions. Immunostaining for estrogen receptor alpha (ERalpha), p53 and estrogen-responsive RING finger protein (Efp) was also carried out. Immunohistochemically, expression of 14-3-3sigma was seen in 92% UDH lesions and gradually decreased from 65% in DCIS to 23% in IDC. The expression of ERalpha decreased gradually from UDH to DCIS to IDC, while p53 showed an inverse staining pattern to that of ERalpha. The expression of Efp showed no significant difference among the three breast lesions. Hence, the present immunohistochemical study confirmed 14-3-3sigma as a tumor suppressor in breast carcinogenesis. A similar immunohistochemical analysis was then carried out on columnar cell hyperplasia with atypia (CCHA), in which the expression pattern of tumor suppressor 14-3-3sigma, ERalpha and p53 suggested that it might be possible that CCHA is a precancerous lesion.     

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。     

GSTP1 promoter hypermethylation is an early event in breast carcinogenesis

Promoter hypermethylation in precursor lesions of the breast cancer may be biomarkers of cancer risk and targets for cancer chemoprevention. Pi-class glutathione-S-transferases (GSTP1) is inactivated by promoter hypermethylation in invasive breast cancers. However, little is known about epigenetic silencing of GSTP1 gene by promoter hypermethylation in precursor lesions. To determine the significance of GSTP1 promoter hypermethylation in breast carcinogenesis, methylation status of GSTP1 gene was studied by nested methylation-specific polymerase chain reaction, and GSTP1 expression was studied by immunohistochemistry in invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS), usual ductal hyperplasia (UDH), and normal breast tissue. GSTP1 promoter hypermethylation was detected in 4/24 (16.7%) of UDH, 18/49 (36.7%) of DCIS, and 14/36 (38.9%) of IDC. No hypermethylation was detected in normal breast tissues. GSTP1 promoter hypermethylation was found to be progressively elevated during breast carcinogenesis (p < 0.01). GSTP1 promoter hypermethylation was associated with loss of GSTP1 expression (p < 0.01 for UDH, p < 0.001 for DCIS and IDC). Our results suggest that GSTP1 promoter hypermethylation is an early event in breast carcinogenesis and appears to functionally silence GSTP1 expression. GSTP1 promoter hypermethylation in the precursor lesions of breast cancer may be used as a target for cancer chemoprevention.     

乳腺癌和乳腺导管内增生性病变Notch1基因甲基化的检测及临床意义

目的 探讨Notch1基因甲基化与乳腺浸润性导管癌(IDC)及乳腺导管内增生性病变的相关性.方法 用基质辅助激光解析电离时间飞行质谱仪(MALDI-TOF MS)对89例乳腺IDC、20例导管原位癌(DCLS)、11例不典型导管增生(ADH)及20例普通型导管增生(UDH)组织进行Notch1基因甲基化的定量检测.采用...     

Nuclear cytometric changes in breast carcinogenesis

Breast cancer is thought to originate through progressively aberrant precursor lesions, paralleled by increasing morphological changes. The aim of this study was to quantify nuclear features by image cytometry in invasive breast cancer and its early (hyperplasia) and late (ductal carcinoma in situ) precursor lesions, in order to objectively describe nuclear changes in the spectrum of proliferative intraductal and invasive breast lesions. Image cytometry was performed on tissue sections of 20 samples of normal breast tissue, 71 of usual ductal hyperplasia (UDH), nine of atypical ductal hyperplasia (ADH), and 11 of well-differentiated and 13 of poorly differentiated ductal carcinoma in situ (DCIS) lesions. The invasive breast carcinomas consisted of 19 well-differentiated and 24 poorly differentiated lesions. Through the spectrum from normal breast tissue to invasive carcinoma, progressive changes in many nuclear features were measured. Significant differences were found between nuclei of florid ductal hyperplasia compared with mild and moderate ductal hyperplastic lesions, suggesting that florid ductal hyperplasia may be a more advanced lesion than assumed and may contain cancer precursor cells. No differences were found between ADH and well-differentiated DCIS, suggesting that these lesions are closely related. Feature values of well-differentiated DCIS were comparable to values found in well-differentiated invasive carcinoma and the same applied to poorly differentiated DCIS and invasive lesions. These results support the hypothesis that breast cancer develops through different routes of progression, one leading to well-differentiated invasive cancer through well-differentiated DCIS, and one leading to poorly differentiated invasive cancer through poorly differentiated DCIS. In conclusion, image cytometry reveals progressive changes in nuclear morphological and subvisual chromatin distribution features in the spectrum from intraductal proliferations to invasive breast cancer. This provides evidence for a progression from usual to atypical ductal hyperplasia and then to invasive cancer, through different routes for well-differentiated and poorly differentiated lesions.     

Cytokeratin 5/6 immunohistochemistry assists the differential diagnosis of atypical proliferations of the breast

AIMS: This study was performed to determine the diagnostic value of keratin 5/6 (CK 5/6) immunophenotyping on routinely processed breast tissues. METHODS AND RESULTS: Six hundred and ninety-nine breast lesions, including normal tissues as well as benign and malignant lesions in 321 formalin-fixed, paraffin-embedded samples from 158 different patients were investigated immunohistochemically, following wet autoclave pre-treatment for antigen retrieval. In normal breast tissues, both myoepithelial and luminal epithelial cells expressed CK 5/6 in varying amounts. While myoepithelial immunoreactivity was most pronounced in the duct system, luminal epithelial immunoreactivity was strongest in the terminal duct lobular units. In ductal hyperplasias (DH), luminal epithelial cells predominantly revealed CK 5/6 immunoreaction. In contrast, neoplastic epithelial cells in atypical ductal and lobular hyperplasias (ADH and ALH) lacked such an expression, whereas in ductal in-situ carcinomas (DCIS) and in infiltrating ductal carcinomas 3.7% and 7.7%, of the cases respectively, showed positive immunostaining for CK 5/6. CONCLUSIONS: Immunophenotyping of keratin 5/6 expression can be helpful in the diagnosis of atypical hyperplasias and in-situ carcinomas of the breast. It is particularly valuable in the differential diagnosis between benign and atypical proliferative lesions.     

Utility of cytokeratin 5/6 and high-molecular-weight keratin in evaluation of cauterized surgical margins in excised specimens of breast ductal carcinoma in situ

Evaluation of the surgical margins of excision specimens for ductal carcinoma in situ (DCIS) of breast is challenging due to cautery artifact introduced in the specimen at the time of surgery. Cautery destroys the cytoarchitectural features at the tissue margins and makes the distinction between usual ductal hyperplasia (UDH) and DCIS difficult. Previous studies have shown the value of immunohistochemical staining for cytokeratin 5/6 (CK5/6) and high-molecular-weight keratin (HMWK) in distinguishing UDH from DCIS. We hypothesized that staining for CK5/6 and HMWK (34bE12) may be helpful in evaluating the cauterized surgical margins, given the 2 antibodies follow the same pattern as described in the preserved foci of the 2 entities. Forty-three excised breast specimens were stained for CK5/6 and HMWK (34bE12). Study material was divided into 5 groups: DCIS without cautery artifact, UDH without cautery artifact, UDH with cautery artifact, DCIS with mild-to-moderate cautery artifact morphologically recognizable as involving the surgical margin on hematoxylin and eosin stain, and DCIS with severe cautery artifacts precluding the evaluation of surgical margins on hematoxylin and eosin stain. A comparative evaluation of pattern, extent, and intensity of the 2 immunostains was done. Our results strongly suggest that antibodies for CK5/6 and HMWK (34bE12) may be useful in determining the presence of DCIS at surgical margins even in the event of severe cautery artifact.     

New trends of immunohistochemistry for making differential diagnosis of breast lesions

Immunohistochemistry is widely used for pathological diagnosis of breast lesions. Other than hormone receptors and HER2/neu analysis for primary breast carcinomas, several markers may be useful for differential diagnoses, although in limited situations. To decide the malignant potential of intraductal proliferative lesions, analysis for the staining pattern of cytokeratins may be a good reference. Most ductal carcinoma in situ cases are diffusely positive for luminal cell markers (CK8, CK18, CK19), but negative for basal cell markers (CK5/6 and CK14). However, usual ductal hyperplasia may show the mosaic staining patterns for any of these markers, which may indicate a heterogeneous cell population in benign lesions. Myoepithelial markers (α-SMA, myosin, calponin, p63, CD10) are almost consistently positive for benign papillomas but they do not completely distinguish intraductal papillary carcinomas. Preservation of myoepithelial layer is the diagnostic key when looking at benign sclerosing lesions, including carcinoma with pseudoinvasive structures. E-cadherin is mostly positive for ductal carcinomas but negative for lobular carcinomas. Some of the lobular carcinomas are positive for 34βE12, but they are consistently negative for CK5/6. Comparison with histopathological findings of hematoxylin and eosin is essential to make proper diagnosis in the individual case.