3-D analysis of intraductal spreading of breast cancer based on expression of protooncogenes and tumor-associated antigens : Application in breast conserving surgery

基于原癌基因和肿瘤相关抗原表达的乳腺癌导管内扩散的 3-D 分析：在保乳手术中的应用

• 批准号: 04670721
• 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: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670721/
• 关键词: breast cancer; breast conserving surgery; in situ carcinoma; intraductal spreading; protooncogene; 3-D mapping; tumor-associated antigen; 3次元マッピング

[Introduction]Intraductal spreading of ductal carcinoma has been a controversial issue in breast conserving surgery for breast cancer patients. The definition of intraductal spreading of carcinoma becomes an important factor for the dicision-making, but little is known about the biological significance of the intraductal proliferative lesions. To define whether any morphologic and/or biologic features of the intraductal lesions exist we investigated histopathologic characteristics of the lsions using a sequential slicing of the tissues with 3-D reconstruction, and biologic characteristics based on expression of cell surface antigens and protooncogenes.[Materials and Methods]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 MUCI, TAG-72 and AM … More antigens, and protooncogene products, c-erbB-2 and ras p21.[Results and Discussion]Using a computer-assisted 3-D mapping analysis we have confirmed our previous observations that breast carcinoma originates from terminal duct-lobular unit (TDLU) and extends intraductally toward its large ducts. The computer-assisted data have also demonstrated that the neoplastic lesions extend discontinuously from TDLU to large ducts. We have proposed the definition of intraductal spreading of carcinoma (ISC) in comparison with extensive intraductal component (EIC) which was previously described by Schnitt et al., Cancer, 1984, as carcinoma in situ is present clearly extending beyond TDLU, or present prominently within large ducts.Among the protooncogenes and tumor-associated antigens examined in our study MUC1 and AM antigens were found to be expressed in carcinoma in situ as well as in atypical epithelial hyperplasias which basically consist of ISC in breast cancer. The result together with the evidence that ras p21 is involved in multistep of carcinogenesis in breast cancer indicates that the intraductal spreading may have a malignant potential.Not only mastectomy, but radiation therapy should be considered for the additional treatments to the ISC-positive patients, although, it is still controversial whether the intraductal component is radiosensitive or not. Further investigations should be continued to dwell on questions of extension, occult invasion, multicentricity, or features possibly associated with breast conserving surgery for patients with intraductal spreading. Less

[导言]在乳腺癌患者的保乳手术中，导管内扩散一直是一个有争议的问题。肿瘤导管内扩散的定义成为决策的重要因素，但对导管内增生性病变的生物学意义知之甚少。为了确定是否存在导管内病变的任何形态和/或生物学特征，我们采用连续切片三维重建的方法研究了乳腺导管内病变的组织病理学特征，以及基于细胞表面抗原和原癌基因表达的生物学特征。[材料和方法]通过计算机辅助三维标测，对乳腺癌患者的手术标本进行研究，以确定肿瘤的起源和扩散。对其中一些标本进行免疫组织化学染色，以识别肿瘤相关抗原，包括MUCI、TAG-72和AM…更多的抗原和原癌基因产物，c-erbB-2和ras p21。[结果和讨论]利用计算机辅助的三维标测分析，我们证实了我们先前的观察结果，即乳腺癌起源于末梢导管-小叶单位(TDLU)，并向其大导管延伸。计算机辅助数据还表明，肿瘤病变从TDLU不连续地延伸到大导管。我们提出了导管内扩散癌(ISC)的定义，与Schnitt等人早在1984年所描述的广泛导管内扩散(EIC)相比，因为原位癌明显地延伸到TDLU之外，或明显地存在于大导管内。在我们研究的原癌基因和肿瘤相关抗原中，MUC1和AM抗原在乳腺癌的原位癌和非典型上皮增生症中都有表达，这两种抗原在乳腺癌中基本上由ISC组成。这一结果与ras-p21参与乳腺癌多步骤癌变的证据相结合，提示导管内扩散可能具有恶性潜能。对于ISC阳性的患者，不仅应考虑乳房切除，还应考虑放射治疗，尽管导管内成分是否对放射敏感仍存在争议。对于导管内扩散的患者，应继续进行进一步的研究，重点放在扩张、隐匿性侵犯、多中心性或可能与保乳手术相关的特征上。较少

项目成果

原田雄功: "新しい乳癌関連抗原の解析と本抗原を標的とした臨床応用への展開" 乳癌基礎研究. 3. 57-60 (1993)

Yusuke Harada：“一种新的乳腺癌相关抗原的分析和针对该抗原的临床应用的开发”《乳腺癌基础研究》3. 57-60 (1993)。

Hiraizumi S: "Altered glycosvlation of membrane glycoprotiens associated with human mammary carcinoma." Jpn.J.Cancer Res.,. 83. 1063-1073 (1992)

Hiraizumi S：“与人类乳腺癌相关的膜糖蛋白糖基化的改变。”

Ohuchi N,: "Improved detection rate of early breast cancer in mass screening combined with mammography." Jpn.J.Cancer Res.,. 84. 807-812 (1993)

Ohuchi N，：“大规模筛查结合乳房X光检查提高了早期乳腺癌的检出率。”

Ohuchi N: "Improved detection rate of early breast cancer in mass screening combined with mammography." Jpn.J.Cancer Res.,. 84. 807-812 (1993)

Ohuchi N：“大规模筛查结合乳房X光检查提高了早期乳腺癌的检出率。”

古田昭彦: "乳癌の発生と進展に関する病理組織学的研究" 乳癌基礎研究. 3. 3-5 (1993)

古田明彦：“乳腺癌发生和进展的组织病理学研究”《乳腺癌基础研究》3. 3-5 (1993)。