| Budget Amount *help |
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
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| Research Abstract |
A.Atypical cystic lobules of the breast, an early stage of low grade ductal carcinoma in situ.
The authors describe the characteristics of atypical cystic lobules (ACLs), which represent a step in the formation of low-grade ductal carcinoma in-situ. The authors defined ACLs as a proliferation of luminal cells showing low-grade cytological atypia without architectural atypia. ACLs were compared with conventional hyperplasia, low-grade ductal carcinoma in-situ and lobular neoplasia. 1) In about forty percent of the cases, atypical cystic lobules merged with fully established micropapillary/cribriform ductal carcinoma in-situ. 2) Immunohistochemical staining for hormone receptors, keratin nineteen, and cyclin D1 revealed that atypical cystic lobules demonstrate a consistent immunophenotype, which differs from the pattern shown by normal lobules and benign lesions and matches the one of low-grade ductal carcinoma in-situ. 3) ACLs are sometimes calcified. Osteopontin-positive histiocytes wer
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e infiltrated in all the Kossa-positive (type II microcalcification) cribriform and comedo type carcinomas and ACLs. The similarities in the cytological and immunohistochemical features, the close proximity of the two type of proliferation and the similarities with respect to the types of calcification suggest that atypical cystic lobules represent an early stage in the formation of certain types of low-grade ductal carcinoma in-situ.
B.Microcalcification of carcinoma in situ and atypical cystic lobules of the breast with infiltration of macrophages with osteopontin.
Abstract
We studied the pattern of calcification and the expression of osteopontin (OP) protein and mRNA by the noninvasive components i of twenty breast cancers and sixteen atypical cystic lobules (ACLs). Ten breast cancers (Cr type) showed low-grade cribriform carcinoma in-situ containing secretory material ; the remaining ten cancers (Co type) displayed high-grade carcinoma in-situ with central necrosis. Hematoxylin-eosin and Kossa staining revealed calcium hydroxyapatite calcifications in 80% of Cr type carcinomas, 50% of Co type carcinomas and 56% of ACLs. Immunohistochemical staining demonstrated OP protein in intraluminal secretory material, necrotic debris, or stroma and in histiocytes in all the Kossa-positive carcinomas and ACLs. In situ hybridization revealed OP mRNA mainly in the histiocytes and especially in those near the calcifications. The close relation between hydroxyapatite crystals and OP producing histiocytes suggests that these cells change the microenvironment in a way that facilitates the crystallization of calcium. The similarity in the patterns of osteopontin expression by ACLs and Cr type ductal carcinomas in-situ suggests that the same mechanism gives rise to the calcifications seen in both lesions.
C.Expression of Steroid receptor co-activator (SRC)-1 and SRC-3 (=amplified in breast cancer, AIB1) in several breast lesions including precursor lesions.
We have tried to detect expression of SRC-1 and SRC-3 in various lesions in the breast, especially in in situ carcinoma and atypical cystic lobules (ACLs) and conventional hyperplasia. SRC-1 was demonstrated almost all nuclei, benign and malignant, in the breast in contrast that estrogen receptor was observed in partial segregated nuclei in proliferative conditions. SRC-1 was partially demonstrated in some nuclei of the high-grade invasive carcinoma. Less
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