Biological characteristics and therapeutic response of intraductal component of breast cancer

乳腺癌导管内成分的生物学特性和治疗反应

• 批准号: 06671178
• 负责人: OHUCHI Noriaki
• 金额: $ 1.28万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06671178/
• 关键词: breast cancer; breast conserving surgery; intraductal spread of carcinoma; protooncogene; 3-D mapping; tumor-associated antigen; MUC1; sialyl-Tn

[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

肿瘤相关抗原MUC 1、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）定义为导管内癌扩散超出终末导管小叶单位（TDLU）并进入大导管的状态。我们根据乳腺癌在乳腺导管-小叶系统中的程度提出了ISC分级，并显示了它与保乳手术后癌残留的密切相关性。乳腺导管内癌的范围也被认为是保乳治疗后局部复发的一个危险因素。本研究旨在探讨乳腺癌在导管内扩散过程中，导管内癌组织成分的生物学特征。[材料与方法]对40例乳腺癌患者行乳腺部分切除术后的标本进行肿瘤三维定位 ...更多信息 或沿着与导管-小叶系统相连。使用单克隆抗体DF 3（抗MUC 1）、B72.3（抗唾液酸-Tn）、DO 7（抗p53）和多克隆抗体SV 2 -61（抗c-erbB-2）对切割成5 μ m厚的组织标本进行免疫组织化学分析。将标本分为两组：高度ISC和低度ISC。[结果与讨论]在ISC程度高的标本中，c-erbB-2和p53蛋白表达无明显增强。MUC 1和sialyl-Tn在高度ISC的标本中表达增强，MUC 1在高度ISC的标本中表达率为35%，在低度ISC的标本中表达率为18%; sialyl-Tn在高度ISC的标本中表达率为25%，在低度ISC的标本中表达率为0%。此外，在ISC程度高的标本中，MUC 1和sialyl-Tn抗原的阳性率为55%，而ISC程度低的标本中，MUC 1和sialyl-Tn抗原的阳性率为18%（P<0.05）。研究了乳腺癌患者的手术标本，使用计算机辅助的3-D映射来定义癌的起源和导管内扩散的部位。肿瘤相关抗原MUC 1、TAG-72、AM和原癌基因产物c-erbB-2、rasp 21的免疫组化染色结果提示，MUC 1和sialyl-Tn抗原在乳腺癌向导管内转移时均有表达，提示MUC 1和sialyl-Tn抗原的表达可作为乳腺癌保乳治疗后局部复发的预测指标。观察到的ISC等级越高，认为进展阶段越严重，因为MUC 1和sialy 1-Tn抗原通常在晚期乳腺癌患者的组织或血清中增强。少

项目成果

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