森 昌造 東北大学, 医学部, 教授 (70004877)
TAKAHASHI Toru Tohoku Univ., Res Inst. Cancer Aging Professor, 加齢医学研究所, 教授 (10004590)
HIRAKAWA Hisashi Tohoku Univ., Sch. of Med. Assistant Prof., 医学部附属病院, 助手 (10250763)
|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1995 : ¥400,000 (Direct Cost : ¥400,000)
Fiscal Year 1994 : ¥1,600,000 (Direct Cost : ¥1,600,000)
[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
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