Moinfar F, Man Y G, Lininger R A, Bodian C, Tavassoli F A
Department of Gynecologic and Breast Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Am J Surg Pathol. 1999 Sep;23(9):1048-58. doi: 10.1097/00000478-199909000-00007.
A variety of studies have investigated the role of low molecular weight (LMW) and high molecular weight (HMW) cytokeratin (CK) expression in the normal breast and invasive breast carcinomas. A few studies with small numbers of cases have addressed this issue in intraductal proliferations of the breast. This study investigates the expression of these CKs in a large series of ductal intraepithelial neoplasias of the breast. We examined 150 ductal carcinomas in situ (DCIS), 35 cases of intraductal hyperplasia (IDH), and 15 cases of atypical intraductal hyperplasia (AIDH). Immunohistochemistry was performed using monoclonal antibodies against CK-34betaE12 (HMW CK), CK-8, and CK-19 (LMW CK) on formalin-fixed, paraffin-embedded tissue. The intensity (0, +1, +2, +3) and percentage of positive intraductal cells (0-100%) were multiplied to obtain a score from 0 to 300. The immunoprofiles of IDH, AIDH, and DCIS were categorized into four groups showing negative or low (0-60), moderate (61-100), high (101-200), and very high (201-300) scores. All cases of IDH showed an intensely positive reaction (high to very high scores) for CK-34betaE12. In contrast, 90% of the DCIS showed a negative or only focal and weak reaction (negative or low score) for this antigen. The remaining 10% of DCIS showed a positive immunoreaction for CK-34betaE12 with moderate to high scores. All cases of florid IDH and 96% of cases of DCIS expressed CK-8 intensely with high to very high scores. Although CK-19 was strongly expressed in 97% of cases of IDH (high to very high scores), a very high score was also found in 80% of cases of DCIS that were positive for CK-19. Of the 15 AIDHs, 80% had a negative or only focal reaction (negative or low score) for CK-34betaE12 and the remaining 20% had a moderate to high score for this antigen. Although CK-8 was strongly positive in 87% of cases of AIDH (high to very high scores), only 53.5% of AIDHs showed intense positivity for CK-19. The present study clearly shows that the immunoprofile of IDH is different from DCIS as far as HMW CK is concerned. Although florid IDH is characterized by a diffuse and intense immunoreaction for HMW CK, the lack of or only weak positivity for HMW CK (CK-34betaE12) is, in most cases, a hallmark of ductal carcinoma in situ. The immunoprofile of AIDH is very similar to that of DCIS. The expression of CK-8 and CK-19 is not useful in separating the various categories of ductal intraepithelial proliferations of the breast. We recommend the use of CK-34betaE12 as an adjunct in the diagnosis of a variety of problematic intraductal proliferations of the breast.
多项研究探讨了低分子量(LMW)和高分子量(HMW)细胞角蛋白(CK)表达在正常乳腺和浸润性乳腺癌中的作用。少数涉及病例数量较少的研究探讨了乳腺导管内增生中的这一问题。本研究调查了这些CK在大量乳腺导管上皮内瘤变中的表达情况。我们检查了150例导管原位癌(DCIS)、35例导管内增生(IDH)和15例非典型导管内增生(AIDH)。在福尔马林固定、石蜡包埋的组织上,使用抗CK-34βE12(HMW CK)、CK-8和CK-19(LMW CK)的单克隆抗体进行免疫组织化学检测。将导管内阳性细胞的强度(0、+1、+2、+3)和百分比(0 - 100%)相乘,得到0至300的评分。IDH、AIDH和DCIS的免疫表型分为四组,分别显示阴性或低(0 - 60)、中度(61 - 100)、高(101 - 200)和非常高(201 - 300)的评分。所有IDH病例对CK-34βE12均显示强阳性反应(高至非常高评分)。相比之下,90%的DCIS对该抗原显示阴性或仅局灶性及弱阳性反应(阴性或低评分)。其余10%的DCIS对CK-34βE12显示中度至高度阳性的免疫反应。所有旺炽性IDH病例和96%的DCIS病例对CK-8均强烈表达,评分高至非常高。虽然97%的IDH病例中CK-19强烈表达(高至非常高评分),但在CK-19阳性的DCIS病例中,80%也有非常高的评分。在15例AIDH中,80%对CK-34βE12呈阴性或仅局灶性反应(阴性或低评分),其余20%对该抗原呈中度至高度评分。虽然87%的AIDH病例中CK-8呈强阳性(高至非常高评分),但只有53.5%的AIDH对CK-19呈强阳性。本研究清楚地表明,就HMW CK而言,IDH的免疫表型与DCIS不同。虽然旺炽性IDH的特征是对HMW CK呈弥漫性强免疫反应,但在大多数情况下,HMW CK(CK-34βE12)缺乏阳性或仅弱阳性是导管原位癌的一个标志。AIDH的免疫表型与DCIS非常相似。CK-8和CK-19的表达在区分乳腺导管上皮内增生的不同类别方面并无帮助。我们建议将CK-34βE12用作诊断各种有问题的乳腺导管内增生的辅助手段。