Biological characteristics and therapeutic response of intraductal component of breast cancer

【导读】肿瘤相关抗原MUC1、sialyl-Tn等已被证实在乳腺癌中表达。然而，基于抗原或癌基因产物的表达，对导管内癌的生物学意义知之甚少。导管内癌扩散（ISC）被定义为DCIS超出末端导管小叶单位（TDLU）并进入大导管的状态。我们根据其在导管小叶系统的程度提出了ISC分级，并表明其与保乳手术后的癌残留密切相关。此外，导管内癌的范围被认为是保乳治疗后局部复发的预后因素。本研究旨在确定乳腺癌导管内扩散时导管内癌组织的生物学特征。【材料与方法】对40例接受乳腺部分切除术的乳腺癌患者的乳腺标本进行了乳腺导管-小叶系统的三维成像。采用单克隆抗体DF3（抗muc1）、B72.3（抗唾液酸- tn）、DO7（抗p53）和多克隆抗体SV2-61（抗c- erbb -2）对厚度为5 μ m的组织标本进行免疫组化分析。标本分为两组；高ISC度和低ISC度。【结果与讨论】在高ISC度的标本中，c-erbB-2和p53产物的表达均未增强。MUC1和sialyl-Tn在高度ISC的标本中增强；MUC1在高度标本中表达35%，在低度标本中表达18%；sialyl-Tn在高度标本中表达25%，在低度标本中表达0%。此外，55%的高ISC度标本显示MUC1和sialyl-Tn抗原，18%的低ISC度标本显示MUC1和sialyl-Tn抗原（P<0.05）。研究了来自乳腺癌患者的手术标本，使用计算机辅助的三维绘图来确定癌的起源位置和导管内扩散。部分标本经免疫组织化学染色，抗体可识别肿瘤相关抗原，包括MUC1、TAG-72和AM抗原，以及原癌基因产物c-erbB-2和ras p21。结果提示MUC1和sialyl-Tn抗原随癌向导管内扩散而表达，抗原表达可预测保乳治疗后局部复发。随着MUC1和sialy1-Tn抗原在晚期乳腺癌患者的组织或血清中经常增强，ISC分级越高，则认为进展期越长。少

[Introduction] Tumor-associated antigens including MUC1, sialyl-Tn have been shown to be expressed in breast cancer. Little is known about biological significance of intraductal carcinoma, however, on the basis of expression of antigens or oncogene products. Intraductal spread of carcinoma (ISC) was defined as a state in which DCIS was extending beyond terminal duct-lobular unit (TDLU) and into large ducts. We have proposed ISC grade based on its extent in duct-lobular system and shown how closely it correlated with carcinoma residue after breast conserving surgery. Also, extent of intraductal carcinoma has been considered to be a prognosic factor for local recurrence after breast conserving therapy. This study was intiated to define any biological features exist in intraductal component of breast carcinoma tissues as carcinoma spreads intraductally.[Materials and Methods] Fourty specimens from breast cancer patients receiving partial mastectomy were subjected to 3-D mapping of the tum … More or along with duct-lobular system. Immunohistochemical analysis using monoclonal antibodies DF3 (anti-MUC1), B72.3 (anti-sialyl-Tn), DO7 (anti-p53), and polyclonal antibody SV2-61 (anti-c-erbB-2) was performed on tissue specimens cut at 5 mum in thickness. The specimens were divided into two groups ; high degree of ISC and low degree of ISC.[Results and Discussion] No enhanced expression of c-erbB-2 or p53 products was found in specimens with high ISC degree. MUC1 and sialyl-Tn were intensified, however, in specimens with high degree of ISC ; MUC1 was expressed in 35% of specimens with high degree vs18%with low degree, and sialyl-Tn was expressed in 25% of specimens with high degree vs 0% with low degree. Furthermore, 55% of specimens with high ISC degree demonstrated either of MUC1 and sialyl-Tn antigens, whereas 18% with low degree showed either of the antigens (P<0.05). Surgical specimens from breast cancer patients were investigated to define the site of origin and intraductal spreading of carcinoma using a computer-assisted 3-D mapping. Some of the specimens were immunohistochemically stained with antibodies which recognize, tumor-associated antigens including MUC1, TAG-72 and AM antigens, and protooncogene products, c-erbB-2 and ras p21.The results suggest that MUC1 and sialyl-Tn antigens are expressed as carcinoma extends intraductally, and that the antigen expression may predict local recurrence after breast conserving therapy. The higher the ISC grade observed, the more progressed phase is considered, as MUC1 and sialy1-Tn antigens are often enhanced in tissue or serum of the patients with advanced breast cancer. Less