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

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[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